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E. Brambilla
Moderator of
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MO26 - Anatomical Pathology II (ID 129)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Pathology
- Presentations: 15
- Moderators:E. Brambilla, V.L. Capelozzi
- Coordinates: 10/30/2013, 10:30 - 12:00, Bayside 105, Level 1
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MO26.01 - Comparison of outcomes for patients with “Bronchioloalveolar Carcinoma (BAC)” defined by the IASLC classification versus the AJCC staging system (ID 3414)
10:30 - 10:35 | Author(s): C.L. Wilshire, B.E. Louie, M.P. Horton, S. Deen, J.L. Kramer, R.W. Aye, A.S. Farivar, H.L. West, J.A. Gorden, E. Vallieres
- Abstract
- Presentation
Background
Integration of the proposed IASLC classification of adenocarcinomas (ACA) into TNM staging has been challenging for pathologists. Until recently, at Swedish, we staged patients per the AJCC staging and separately described lesions with a BAC component placing them into 3 groups based on the percent of ACA invasion. But, we found this was not a good predictor of survival. We aimed to more clearly define this population by comparing patients reclassified according to the proposed IASLC classification and the AJCC 7[th] edition staging to determine if they could be integrated as a single staging system.Methods
We retrospectively reviewed patients with BAC from 2000-2012 and classified them according to the IASLC classification as ACA in situ (AIS), minimally invasive ACA (MIA) or lepidic predominant ACA (LPA) and according to the AJCC 7[th] edition staging (stage I, II or III). We then reclassified these patients separating AIS and MIA as stage 0 in the AJCC 7[th] edition staging.Results
We evaluated 145 consecutive patients with a median follow-up of 30 months. Using IASLC [AIS (N=23), MIA (N=18), LPA (N=104)]; local recurrence rates were: AIS (4%), MIA (11%) and LPA (2%). Regional (8%) and distant (10%) recurrences were only with LPA. Disease-free survival in patients with AIS (96%) and MIA (89%) was higher versus patients with LPA (80%). Five year cancer-specific survival was 100% for patients with AIS and MIA while it was 84% for LPA patients. Using AJCC 7[th] edition [I (N=125), II (N=12), III (N=8)]; recurrence rates were local: stage I (3%), stage III (13%). Regional: stage I (5%), stage II (8%), stage III (13%); and distant: stage I (6%), stage II (17%), stage III (13%). Stage I disease-free survival was 86%, stage II 75% and stage III 61%. Five year cancer-specific survival was stage I 90%, stage II 81% and stage III 60%. Separating AIS and MIA as stage 0 [0 (N=42), I (N=84), II (N=11), III (N=8)]; local recurrence rates were: stage 0 (7%), stage I (1%), stage III (13%). Regional: stage I (7%), stage II (9%), stage III (13%); and distant: stage I (10%), stage II (18%), stage III (13%). Disease-free survival was higher in stage 0 (93%) compared to stage I (82%), stage II (73%) and stage III (61%). Five year cancer-specific survival was 100% for stage 0, while it was lower for stage I 84%, stage II 80%, and stage III 60%, p<0.05.Conclusion
The IASLC/ATS/ESR classification system appears to better discriminate patients with BAC compared to current AJCC staging. The results also suggest that patients with AIS and MIA may be classified as stage 0 in the AJCC staging system based on favorable outcomes and survival.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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- Abstract
- Presentation
Background
The purpose of this study is to validate the prognostic impact and the frequency of EGFR mutation in lung adenocarcinoma of Japanese patients based on new lung adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS).Methods
We reclassified 486 adenocarcinomas according to the new classification. The percentage of each histopathological subtype and the predominant pattern were determined. EGFR mutation also was investigated 241 of 486 adenocarcinomas. The relationship between these results and clinicopathological backgrounds was investigated statistically.Results
The histopathological assessment according to the IASLC/ATS/ERS classification showed that 8.4% (n = 41) of the cases were adenocarcinoma in situ (AIS) ; 9.2% (n = 45) were minimally invasive adenocarcinoma (MIA) ; 18.3% (n = 89) were lepidic predominant ; 20.4% (n = 99) were acinar predominant ; 28.0% (n = 136) were papillary predominant ; 10.5% (n = 51) were solid predominant ; 2.3% (n=11) were micropapillary (MP) predominant, and 2.9% (n=14) were invasive mucinous adenocarcinoma (IMA). In univariate analysis, the patients with AIS and MIA subtypes had neither recurrence nor death within the follow-up periods. This was followed by the patients with lepidic predominant. The patients with papillary predominant, those with acinar predominant and those with IMA showed almost similar disease-free survival. The patients with solid predominant and MP predominant showed worse disease-free survival (Figure). Multivariate analysis showed that the new classification was an independent predictor of disease-free survival (Hazards ratio: 2.59; 95% confidence interval: 1.69-3.96; p<0.001). EGFR mutation was detected in 131 of 241 adenocarcinomas (54.4%). The each prevalence of EGFR mutation of AIS/MIA/Lepidic/Papillary/Acinar/Solid/MP/IMA was 62.1%/60%/77.1%/50%/49%/27.8%/42.9%/0%.Figure 1Conclusion
The new IASLC/ATS/ERS adenocarcinoma classification is very useful predictive marker to plan and determine a therapeutic strategy for lung adenocarcinoma.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.03 - In Patients with Stage I Lung Adenocarcinoma, Tumor Budding Is a Significant Prognostic Factor for Recurrence, Independent of the IASLC/ATS/ERS Classification, and Correlates with a Protumor Immune Microenvironment (ID 2917)
10:40 - 10:45 | Author(s): K. Kadota, Y. Yeh, N.P. Rizk, V.W. Rusch, P.S. Adusumilli, W.D. Travis
- Abstract
- Presentation
Background
In 2011, the IASLC/ATS/ERS proposed a new classification for lung adenocarcinoma (ADC) that has powerful prognostic value. However, tumors in each subtype may still include heterogeneous prognostic subgroups - especially in the acinar, papillary, and solid subtypes, in which the majority of tumors are classified. Recently, immune markers such as CD markers and cytokines have been identified as prognostic factors in lung cancer. In this study, we investigate whether tumor budding further stratifies prognosis for stage I lung ADC, independent of the IASLC/ATS/ERS classification, and whether it correlates with prognostic immune markers.Methods
All available tumor slides from patients with therapy-naive, surgically resected solitary stage I lung ADC (1995-2009) were reviewed (n=1038). Tumors were classified according to the IASLC/ATS/ERS classification. Mitoses were counted at 10 high-power fields (HPFs) (x400 magnification). Tumor budding (tumor nest composed of <5 cells) was assessed, at 10 HPFs (x200 magnification), in areas with the smallest tumor nests and was graded by the maximum number of budding : 0, 0/HPF; 1, 1-4/HPF; 2, 5-9/HPF, and 3, ≥10/HPF. Tissue microarrays were constructed from tumoral and stromal cores, and immunostaining for CD3, FoxP3, IL-7R, and IL-12Rβ2 was performed. Lymphocytes positive for CD3 and FoxP3 were scored in tumor and stroma, and tumors were classified using our recently reported FoxP3/CD3 risk index (JCO 2013). Tumoral expression of IL-7R and IL-12Rβ2 was dichotomized by the sum of intensity (0-3) and distribution (1, 1%-50%; 2, >50%) scores: negative (total score <1) and positive (≥1). Recurrence-free probability (RFP) was estimated using the Kaplan-Meier method; multivariate analyses were performed using the Cox proportional hazards model.Results
RFP was lowest for patients with budding grade 3 (n=180; 5-year RFP, 69%; p<0.001), followed by grade 2 (n=139; 75%), 1 (n=189; 81%), and 0 (n=530; 89%). Budding grade was dichotomized into negative (grades 0-1) or positive (grades 2-3) using colorectal cancer criteria. The RFP for patients with positive budding (n=319; 5-year RFP, 72%) was significantly lower than that for patients with negative budding (n=719; 87%; p<0.001), which was confirmed in a subgroup analysis limited to stage IA (p=0.004) and IB (p<0.001) patients. Tumor budding further stratified RFP in patients with acinar (p<0.001), papillary (p=0.027), and solid (p=0.015) tumors. Budding was more frequently observed in tumors with high-grade histology (solid and micropapillary; p<0.001), lymphovascular invasion (p<0.001), and high mitotic count (p<0.001). Tumor budding was positively correlated with stromal CD3+ lymphocytes (p<0.001), stromal FoxP3+ (p<0.001), FoxP3/CD3 risk index (high FoxP3, low CD3) in stroma (p<0.001), and tumoral IL-7R expression (p<0.001). In multivariate analysis, tumor budding was an independent prognostic factor for recurrence (HR=1.13; p=0.002).Conclusion
Tumor budding was a significant prognostic factor in stage I lung ADC, independent of IASLC/ATS/ERS classification, and it correlated with a protumor immune microenvironment (high FoxP3+ lymphocyte infiltration and high IL-7R expression). These findings may inform therapeutic decisions and stratify patients for additional therapy, including immunotherapy.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.04 - Reclassification of Resected Non-Small Cell Lung Carcinomas Originally Diagnosed as Squamous Cell Carcinoma, after Reevaluation Using Immunohistochemical Analysis (p40, p63, TTF-1, and Napsin A): Memorial Sloan-Kettering Cancer Center Experience (ID 2905)
10:45 - 10:50 | Author(s): K. Kadota, J. Nitadori, V.W. Rusch, N. Rekhtman, I.S. Sarkaria, P.S. Adusumilli, W.D. Travis
- Abstract
- Presentation
Background
Currently, non-small cell lung carcinomas (NSCLCs) are mainly classified by histologic analysis and mucin staining: (1) squamous cell carcinoma (SCC) shows keratinization and intercellular bridges; (2) adenocarcinoma shows lepidic, acinar, papillary, micropapillary, or solid pattern, with mucin production; and (3) large cell carcinoma lacks these findings. However, recent studies have shown promising improvements in the classification of NSCLC with immunostain-based markers, including p40 and thyroid transcription factor–1 (TTF-1). In this study, we investigate the use of immunohistochemical analysis in reclassifying NSCLCs originally diagnosed as SCCs.Methods
All available tumor slides from patients with therapy-naive, surgically resected solitary NSCLCs originally diagnosed as SCC (1999-2009) were reviewed. Tissue microarrays were constructed with 3 cores (n=480), and immunostaining for p40, p63, TTF-1 (clone 8G7G3/1), TTF-1 (SPT24), napsin A, chromogranin A, synaptophysin, and CD56 was performed. Immunoreactivity was scored semiquantitatively by staining intensity (weak, moderate, or strong) and percentage of positive tumor cells (diffuse, ≥50%; focal, <50%). Tumors were first grouped by p40 and TTF-1 (8G7G3/1) status: (1) group A (favor SCC): p40 (+) and TTF-1 (8G7G3/1) (-); (2) group B (favor adenocarcinoma): p40 (- or +) and TTF-1 (8G7G3/1) (+); and (3) group C (favor large cell carcinoma): p40 (-) and TTF-1 (8G7G3/1) (-). Immunostain-based tumor classification was then confirmed with histologic findings and other markers.Results
In group A (n=448), 1 tumor was reclassified as adenosquamous carcinoma by histologic findings and focal immunoreactivity for p40, p63, and TTF-1 (SPT24). In group B (n=15), 2 tumors were reclassified as large cell neuroendocrine carcinoma (LCNEC) by neuroendocrine morphologic findings and differentiation (1 as pure LCNEC and the other as combined LCNEC with SCC). In group C (n=17), 6 tumors were confirmed as large cell carcinoma because they lacked adenocarcinoma morphology and TTF-1 [SPT24] expression (2 of these showed focal p63 reactivity without keratinization); 4 were reclassified as large cell carcinoma (favor adenocarcinoma) because they were focally positive for TTF-1 (SPT24) but negative for TTF-1 (8G7G3/1) and napsin A; 2 were reclassified as adenocarcinoma because they were diffusely and strongly positive for TTF-1 (SPT24) but focally (<10%) positive for p63, without keratinization; 3 were reclassified as LCNEC by neuroendocrine morphologic findings and differentiation; and 2 were reclassified as small cell carcinoma by morphologic findings. All tumors finally diagnosed as SCC (n=447) using histologic findings and immunohistochemical analysis were positive for p40 and p63. Among them, 27 tumors were positive for TTF-1 (SPT24) (19 focally and 8 diffusely) but negative for TTF-1 (8G7G3/1), with all showing clear squamous morphologic pattern, thus verifying the greater specificity of the TTF-1 8G7G3/1 clone in SCC.Conclusion
After immunohistochemical reevaluation of 480 NSCLCs originally diagnosed as SCC by classical morphologic analysis, 33 (7%) were reclassified as other histologic types. Immunohistochemical analysis may provide additional valuable information to achieve an accurate diagnosis, particularly in poorly differentiated NSCLCs and in tumors for which the diagnosis of nonkeratinizing SCC is considered.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.05 - DISCUSSANT (ID 3989)
10:50 - 11:00 | Author(s): Y. Ishikawa
- Abstract
- Presentation
Abstract not provided
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MO26.06 - Cell block samples from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) provide sufficient material for ancillary testing in lung cancer. (ID 3262)
11:00 - 11:05 | Author(s): P. Nguyen, E. Viiret, P. Robinson, H. Jersmann, B. Dougherty, I. Birader, I. Parkinson, K. Francis, D. Moffat
- Abstract
- Presentation
Background
Rapid on site examination (ROSE) is encouraged at EBUS-TBNA to improve the yield of this procedure. However, many centres do not have the resources to meet this demand. Due to new therapeutic options in lung cancer, it is not sufficient to merely distinguish between non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Immunohistochemistry (IHC) distinction where possible is now standard practice, as well additional molecular testing where clinically indicated. We investigated the diagnostic yield of smears vs. cell block and the provision of cellular material for ancillary testing.Methods
A retrospective audit of all EBUS-TBNA procedures performed until the end of July 2012 was undertaken. Diagnostic yield on smears versus cell block was recorded. Cell blocks were reviewed by an experienced pathologist to determine diagnostic accuracy and whether IHC and molecular testing were possible.Results
208 procedures were recorded with 101(48.5%) malignant cases, 81(38.9%) benign cases and 26(12.5%) with insufficient sampling. The average number of passes was 4.5. For malignancies, smear diagnosis was possible in 95% of cases and cell block diagnosis in 93.5% (87/93) of cases. There was sufficient material for IHC in 97.7% (85/87) of malignant cases where required. In 79.3% (69/87) of NSCLCs molecular testing was theoretically possible based on the tumour load of samples obtained.Conclusion
Cell blocks are not inferior to smears for diagnostic accuracy and provide sufficient samples for ancillary testing. However, ROSE assists the physician on how best to manage samples for ancillary testing.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.07 - Usefulness of cytological samples for the assessment of ALK rearrangements in NSCLC patients. (ID 2351)
11:05 - 11:10 | Author(s): T. Labiano, M. Zudaire, M. Montañana, J. Echeveste, M. Aguirre, A. Gúrpide, J. Pérez Gracia, S. Martín - Algarra, J. Fusco, M.D. Lozano
- Abstract
- Presentation
Background
ALK gene rearrangement defines a new molecular subtype of NSCLC with response to Crizotinib, (Xalkori®) a dual MET and ALK inhibitor. To date, determination of ALK gene rearrangements has been performed in biopsies and/or surgical specimens. However, advanced lung cancer is often diagnosed by FNA cytology obtained through minimally invasive procedures, and frequently cytological specimens are the only samples available. We assessed the feasibility of determining ALK gene rearrangements in cytological samples.Methods
We studied prospectively 53 cytological samples from 53 NSCLC patients (30 M/23 F) for ALK gene rearrangements by FISH (Abbot dual colour break apart probe). Tumour samples were obtained by bronchoscopy -FNA in 26 cases (49.1%), EBUS-FNA in 7 (13.2%), EUS-FNA in 3 cases (5.7%), CT-FNA in 3 (5.7%), and direct FNA in 6 cases (11.3%). Two cavity fluids (3.8%), 4 imprints from surgical specimens (7.5%), and 2 cellblocks received for consultation (3.8%) were also studied. FISH was performed on Papanicolau stained smears in 15 cases (28.3%), non-stained ThinPrep in 28 cases (52.8%), cell block in 9 cases (17%), and 1 stained ThinPrep. All cases were tested for EGFR and KRAS mutations.Results
Thirty-seven samples (69.8%) were adequate for FISH analysis. Three cases (8.1%) had ALK gene rearrangements: positive cases were non-smoker women with adenocarcinoma, two of them with signet ring cells. One case had a concurrent EGFR mutation in exon 21. FISH study was unsuccessful in 16 cases (30.2%): 10 from Papanicolau stained smears (62.5%), 5 from unstained ThinPrep (31.3%), and 1 from a cell block. Nineteen ThinPrep slides were adequate for FISH analysis (86.4%) as well as 8 out of 9 cell blocks. Correlation cytological / paraffin embedded samples was performed in 4 cases with a concordance rate of 100%.Conclusion
Determination of ALK gene rearrangements in cytological specimens is feasible. It is mandatory an exquisite management and care of the samples to preserve quality. ThinPrep and cell blocks are the most suitable samples for FISH analysis, while Papanicolau stained smears provide poor results. Coexistence of ALK gene rearrangements and EGFR mutations was observed in one case, indicating that such alterations are not necessarily mutually exclusive.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.08 - The concomitant presence of echinoderm microtubule associated protein like 4 - anaplastic lymphoma kinase (EML4-ALK) EML4-ALK fusion gene in EGFR-mutant non-small-cell lung cancer (NSCLC) patients treated with erlotinib or chemotherapy in the EURTAC trial</b> (ID 1109)
11:10 - 11:15 | Author(s): N. Karachaliou, C. Costa, A. Gimenez-Capitan, A. Drozdowskyj, R. Gervais, A. Vergnenegre, F. De Marinis, M. Majem, E. Felip, R. Garcia-Campelo, T. Moran, S. Viteri, A. Gasco, B. Massuti, R. Rosell
- Abstract
- Presentation
Background
Activating mutations in the epidermal growth factor receptor (EGFR) confer sensitivity to gefitinib and erlotinib in patients with NSCLC. However, response is often short-lived, and patients ultimately relapse, indicating that other concomitant actionable mutations could influence outcome in these patients. The EML4-ALK fusion gene has recently been identified in a subset of NSCLCs, but its specific role remains unclear. We have evaluated the frequency and impact of the concomitant presence of EML4-ALK in patients included in the randomized phase III EURTAC trial.Methods
The EURTAC study enrolled 173 EGFR-mutant NSCLC patients who were randomized to receive erlotinib or standard chemotherapy with cisplatin or carboplatin plus docetaxel or gemcitabine. Tumor specimens were available from 95 of these patients for the analysis of EML4-ALK. EML4-ALK variants 1 and 3 (v1, v3) were analyzed by an independent single round of PCR followed by sequencing, using cDNA as a sample.Results
EML4-ALK was detected in 15 samples (15.79%). Nine tumors contained v1 (E13;A20) and six v3 (E6;A20). No significant differences were found in baseline characteristics between patients with and without EML4-ALK. Progression-free survival was 10.4 months (m) for patients harboring the EML4-ALK fusion gene compared to 7.1 m for those without EML4-ALK. Overall survival (OS) was not reached in patients with EML4-ALK, compared to 22.9 m in those without. Complete data on outcome according to treatment arm will be presented.Conclusion
Our findings indicate that the EML4-ALK rearrangement is concomitant with EGFR mutations in a considerable number of NSCLC patients and may affect outcome.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.09 - Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma (ID 2023)
11:15 - 11:20 | Author(s): S. Hirayama, G. Ishii, R. Matsuwaki, Y. Matsumura, K. Aokage, T. Hishida, J. Yoshida, K. Nagai
- Abstract
- Presentation
Background
Stromal cells, including macrophages, lymphocytes and fibroblasts, are known to interact with cancer cells and to produce a specific microenvironment capable of influencing tumor progression. Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 positive TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 positive TAMs and the clinicopathological features of lung squamous cell carcinoma.Methods
We investigated the relationships between the numbers of CD204 positive TAMs and clinicopathological factors, microvessel density (MVD), and the numbers of Foxp3 positive lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 positive TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 positive TAMs.Results
A high number of CD204 positive TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 positive TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 positive TAMs were correlated with the MVD and the numbers of Foxp3 positive lymphocytes. A high number of CD204 positive TAMs was strongly correlated with the tissue expression level of MCP-1. CD204 positive TAMs were shown to be significant independent prognostic factors in a multivariate analysis.Conclusion
CD204 positive TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 positive TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.10 - DISCUSSANT (ID 3990)
11:20 - 11:30 | Author(s): K. Geisinger
- Abstract
- Presentation
Abstract not provided
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MO26.11 - Proposal on incorporating Blood Vessel Invasion into the T classification parts as a practical staging system for stage I Non-small cell Lung Cancer (ID 842)
11:30 - 11:35 | Author(s): Y. Kudo, H. Saji, Y. Shimada, J. Matsubayashi, M. Kakihana, N. Kajiwara, T. Ohira, N. Ikeda
- Abstract
- Presentation
Background
We investigated blood vessel invasion (BVI) as a possible negative prognostic factor in patients with stage I non-small cell lung cancer (NSCLC) according to the 7[th] Edition of the TNM classification.Methods
Between 1999 and 2007, a total of 694 consecutive patients with pathological stage I NSCLC underwent complete resection with systematic lymph node dissection at Tokyo Medical University Hospital. All sections of the specimens were stained by Elastica van Gieson to visualize elastic fibers and were examined to determine the prognostic symptoms of BVI. We statistically analyzed the association between BVI and clinicopathologic factors, as well as clinical outcomes.Results
BVI was detected in 201 patients with stage I NSCLC (29.0%). The 5-year overall survival (OS) rates of the non-BVI and BVI patients were 90.5% and 66.0%, respectively (p < 0.0001). BVI was found to be a significant independent prognostic factor by multivariate survival analysis in stage IA and stage IB NSCLC (HR 2.591, p < 0.001; HR 2.347, p = 0.009, respectively). The 5-year OS rate of patients with BVI was significantly worse than that of patients without BVI in the T1a (94.5% vs 87.5%, p < 0.0001), T1b (82.7% vs 65.9%, p = 0.034), and T2a (90.9% vs 61.8%, p < 0.0001) subgroups.Conclusion
We identified the presence of BVI as an independent poor prognostic factor in patients with stage I NSCLC. In the future revision of the TNM staging system, the routine use of elastic fiber stains in pathological evaluations of lung cancer for BVI determination might be recommended, and tumors with BVI should be upstaged to the higher current T staging.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.12 - Prognostic Impact of Microscopic Vessel Invasion and Visceral Pleural Invasion in Non-small Cell Lung Cancer (ID 2480)
11:35 - 11:40 | Author(s): S. Neri, J. Yoshida, G. Ishii, Y. Matsumura, K. Aokage, T. Hishida, K. Nagai
- Abstract
- Presentation
Background
In non-small cell lung cancer (NSCLC), visceral pleural invasion (VPI) is incorporated as a staging factor in the current TNM classification. Microscopic vessel invasion (MVI: defined collectively as histological blood vessel invasion and lymphatic permeation) has been reported to be a strong independent predictor of poor prognosis, but it has not been incorporated in the TNM classification. We assessed the prognostic significance of MVI as well as VPI.Methods
Between August 1992 to December 2009, 2657 consecutive patients with pathological T1-4N0-2M0 NSCLC underwent complete resection at our institution. We analyzed the prognostic significance of MVI for recurrence in addition to the conventional prognostic factors. The recurrence-free proportion was estimated using the Kaplan-Meier method and differences were analyzed by the log-rank test. Cox regression analyses were used to identify independent risk factors for recurrence.Results
The 5-year recurrence-free proportion for patients with or without MVI was 52.6% and 87.5%, respectively (p < 0.001). On multivariate analysis, MVI, similarly to VPI, was found to be an independently significant predictor of recurrence (HR 2.78). In 1601 patients with pathological stage I disease without adjuvant chemotherapy, MVI and VPI were the two strongest independent predictors of recurrence on multivariate analysis (HR 2.74 and 1.84, respectively). Evident and significant separation of the recurrence-free proportion curves among the following 3 groups according to the number of the two risk factors (VPI and MVI) was observed; both VPI and MVI absent (0), either VPI or MVI present (1), and both VPI and MVI present (2). We compared the recurrence-free proportion of patients stratified by tumor size and the number of the risk factors (0/1/2) (Table 1). The groups of small tumor size without PL and MVI showed the best recurrence-free proportions (T1a_0, T1b_0, and T2a_0). The T1a_1, T1b_1, and T2a_1 subgroups showed poorer outcomes which were comparable with the T2b_0 subgroup. The groups with both PL and MVI, even in small tumor size groups, resulted in poor outcomes equivalent to that of T3_0/1 groups. The T3_2 group showed the poorest outcome equivalent to the T4 group.Conclusion
This study demonstrated that MVI was a significantly independent risk factor for recurrence in resected T1-4N0-2M0 NSCLC patients. We propose the T-classification of tumors with either MVI or VPI (1) should be upgraded to the next T level and that with both MVI and VPI (2) to the second T level (Table 1).Table 1. Incorporation of PL and MVI into T classification
Current (7th) T Classification Tumor Size (cm) No. of VPI and MVI Risk Factors Recurrence-free Proportion at 5 Years (%) OurProposalT T1a ≤ 2 0 92.2 T1 ≤ 2 1 72.2 T2 ≤ 2 2 58.2 T3 T1b > 2, ≤ 3 0 89.6 T1 > 2, ≤ 3 1 64.8 T2 > 2, ≤ 3 2 50.9 T3 T2a > 3, ≤ 5 0 87.8 T1 > 3, ≤ 5 1 61.9 T2 > 3, ≤ 5 2 44.8 T3 T2b > 5, ≤ 7 0 75.9 T2 > 5, ≤ 7 1 49.4 T3 > 5, ≤ 7 2 47.5 T3 T3 > 7 0 58.2 T3 > 7 1 50.6 T3 > 7 2 38.8 T4 Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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- Abstract
- Presentation
Background
The distinction of intrapulmonary metastases from multiple primary tumors is of great clinical importance as it influences staging, prognosis and therapeutic strategy. Although Comprehensive Histologic Assessment (CHA) was recommended by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) to differentiate multiple lung primary non-small cell carcinomas from metastases, the limitations of CHA have been addressed. Lung adenocarcinoma in situ is characterized by noninvasive lepidic growth. Whether this histological characteristic could be served for assessing primary lung cancer has not been well determined. In this study we evaluated the application value of CHA and lepidic growth component (LGC) in distinguishing multiple primary lung cancers from intrapulmonary metastases.Methods
We retrospectively analyzed a cohort of 23 patients with 50 multiple lung tumors. All of the patients have follow up data. The histological evaluation was performed according to 2011 IASLC/ATS/ERS Classification of Lung Adenocarcinoma. The percentage of each tumor subtype in each case was recorded. The intrapulmonary metastases and multiple primary tumors were differentiated based on CHA and LGC (if applicable).Results
According to CHA alone, there were 11 and 12 cases diagnosed as multiple primary tumors and intrapulmonary metastases, respectively. Disease-free interval (DFI) of the 11 patients with multiple primary tumors was ranged from 11 to 110 months and DFI of the 12 patients with intrapulmonary metastases was ranged from 1 to 93 months. There was no statistically significant difference between these two types of patients (P=0.362). According to CHA with inclusion of LGC, 15 and 8 cases were diagnosed as multiple primary tumors and intrapulmonary metastases, respectively. DFI of the 15 and 8 cases were ranged from 11 to 110 months and from 1 to 34 months, respectively. Statistical significance was detected (P=0.034). These results suggested that CHA combining with LGC might have assessment advantage to distinguish multiple primary tumors from intrapulmonary metastases compared to use CHA alone. Figure 1Conclusion
The appearance of adenocarcinoma with LGC might indicate lung primaries. Combining with CHA, LGC could potentially improve diagnosis to differentiate multiple primary tumors and intrapulmonary metastases.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.14 - Histological Prognostic Markers in Squamous Cell Carcinoma of the Lung (ID 2908)
11:45 - 11:50 | Author(s): A. Drilon, C.S. Sima, P.K. Paik, A.L. Moreira
- Abstract
- Presentation
Background
The current IASLC/ERS/ATS classification of pulmonary adenocarcinoma indicates that different patterns of growth in adenocarcinoma are associated with prognostic value. There is however, very little information concerning histological prognostic markers in squamous cell carcinomas of the lung. In contrast to adenocarcinoma, squamous cell carcinoma is more homogeneous histologically. However, the World Health Organization classification of lung tumors recognizes different patterns of growth in squamous cell carcinomas. In this study we evaluated several histological parameters including growth patterns and nuclear features and their association with prognosis in a population of stage 1 squamous cell carcinomas.Methods
A cohort of 165 stage I squamous cell carcinomas of the lung were evaluated. The presence of different histological growth patterns such as papillary, infiltrative, pushing borders, intraalveolar, pseudo-glandular, basaloid, small nest and presence of infiltrating single cells, as well as the cell type (clear cell, transitional, syncytial, and glassy) were evaluated in a semi- quantitative manner by recording the percent of each histological pattern or cell type with 10% increments totaling 100% for tumor. In addition, the presence of peripheral palisading, nuclear features (nuclei size, chromatin patterns, nuclear contour, presence of nucleoli, and mitotic figures), and keratinization were also evaluated. The association of predominant pattern of growth, cell type, and nuclear features with recurrence free survival (RFS), characterized by time to recurrence or death of disease and overall survival (OS) were evaluated.Results
There were 66 women and 97 men in this population with a mean age of 75±9 year old. All patients were smokers. The mean follow-up was of 47.8 months (4 years). Among histological growth patterns, tumors with predominant papillary and pushing borders appear to have a slightly better outcome compared to other predominant patterns of growth (RFS p=0.05 and OS 0.025). It is interesting to note that squamous cell carcinomas with a predominant basaloid growth pattern, which is considered to be a pattern of poor differentiation, did not have worse prognosis copared to other features. There was no association of cell type, nuclear features, presence of palisading or keratinization with prognosis. There was no difference of nuclear features among tumors with different growth patterns and cell types.Conclusion
Squamous cell carcinomas appear to be more homogeneous than adenocarcinomas of the lung despite some histological variances. Evaluation of several histological parameters like growth pattern, cell type, and nuclear features failed to indicate a strong association of any of these parameters with prognosis, with exception of papillary and pushing border growth patterns that when present as predominant patterns of growth were associated with a better prognosis. This suggests that contrary to adenocarcinoma, a histological based grading system may not be easily established for squamous cell carcinomas of the lung.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO26.15 - DISCUSSANT (ID 4020)
11:50 - 12:00 | Author(s): P.A. Russell
- Abstract
- Presentation
Abstract not provided
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Author of
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HOD2 - Mondays Highlights of the Day - Medical Oncology, Biology and Pathology (ID 225)
- Event: WCLC 2013
- Type: Highlight of the Day Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:R. Pirker
- Coordinates: 10/29/2013, 07:00 - 08:00, Bayside Auditorium B, Level 1
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HOD2.3 - Pathology (ID 4041)
07:40 - 08:00 | Author(s): E. Brambilla
- Abstract
- Presentation
Abstract not provided
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O04 - Molecular Pathology I (ID 126)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Pathology
- Presentations: 1
- Moderators:I.I. Wistuba, W.A. Cooper
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Ballroom A, Level 1
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O04.01 - Identification of CD74-NRG1, a new recurrent fusion gene in invasive mucinous lung adenocarcinomas of never smokers (ID 4022)
10:30 - 10:40 | Author(s): E. Brambilla
- Abstract
- Presentation
Background
Lung adenocarcinoma (AD) of patients who have never smoked frequently bear targetable genome kinase alterations, such as EGFR mutations and translocations affecting ALK, ROS1, and RET genes. These mutations correlate with kinase inhibitor sensitivity in mouse models or in patients. Unfortunately, therapeutically relevant kinase alterations are not present in all lung cancer specimens. Thus, additional genome alterations need to be discovered in order to provide a therapeutic opportunity for the remaining patients.Methods
We collected a cohort of 25 AD specimens of never smokers lacking mutations in KRAS or EGFR, in which we performed transcriptome sequencing with the aim of identifying new oncogenic driver genes.Results
We were able to identify known kinase fusions affecting ALK, ROS1 and RET genes in 3 cases each. Moreover, we detected one sample carrying a novel chimeric transcript fusing the first six exons of CD74 to the EGF-like domain of the NRG1 III-β3 isoform, leading to the expression of its EGF-like domain in an otherwise NRG1-negative tumor tissue. The fusion gene was further detected in four additional cases out of 94 pan-negative* ADs of never smokers. In total, all 5 cases were identified in stage I invasive mucinous lung adenocarcinomas (IMA) of never smoker females. This tumor type frequently presents with multifocal unresectable disease, for which no effective treatment has been yet established. IMA is highly associated with KRAS mutations; indeed, out of 15 IMA analysed, 6 carried a KRAS mutation (40%), and 4 the CD74-NRG1 fusion (27%). Given the fact that NRG1 signals through ERBB3 and ERBB4 receptors, we aimed to determine which receptor CD74-NRG1 provides the ligand for. We observed that ERBB4 was not expressed in the index case, while ERBB3 was relatively highly expressed and this expression also correlated with a positive phospho-ERBB3 (p-ERBB3) signal in the tumoral tissue of all 5 CD74-NRG1 positive cases. In order to test if this phosphorylation of ERBB3 was statistically significant, we stained a cohort of 241 ADs and found that p-ERBB3 was only positive in 6 of them (p-value<0.0001). Additionally, although both EGFR and ERBB2 were expressed in the index case, only ERBB2 expression correlated with a p-ERBB2 positive signal. These data suggest that CD74-NRG1 might provide the ligand for ERBB3, which may form heterodimers with ERBB2, since ERBB3 is devoid of intrinsic kinase activity and cannot support linear signaling in isolation. This is in line with previous studies showing that NRG1 induces an oncogenic signal through ERBB2-ERBB3 heterodimers engaging the PI3K-AKT pathway. This was further supported by the activation of the PI3K-AKT, but not the MAPK pathway, in CD74-NRG1 transduced H2052 lung cells, after 24h starvation. *pan-negative: EGFR, KRAS, ALK, HER2, BRAF, ROS1 and RET wild-typeConclusion
Altogether, these data shows that CD74-NRG1 is a new recurrent oncogenic fusion gene, highly associated with IMA of never smokers. It also suggests that CD74-NRG1 fusion protein signals through the ERBB2-ERBB3 receptors complex leading to the activation of the PI3K-AKT pathway, providing a therapeutic opportunity for a tumor type with, so far, no effective treatment.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
