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K.F. To
Moderator of
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O17 - Anatomical Pathology I (ID 128)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Pathology
- Presentations: 8
- Moderators:K. Jones, K.F. To
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 105, Level 1
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O17.01 - Prognostic and predictive value of a new IASLC/ATS/ERS lung adenocarcinoma classification in a pooled analysis of four adjuvant chemotherapy trials: a LACE-Bio study (ID 3255)
10:30 - 10:40 | Author(s): E.M. Brambilla, S. Marguet, G. Le Teuff, S. Lantuejoul, F.A. Shepherd, L. Seymour, R. Kratzke, S.L. Graziano, H. Popper, J. Pignon, R. Rosell, J. Douillard, T. Le Chevalier, J. Soria, M. Tsao
- Abstract
- Presentation
Background
A new IASLC/ATS/ERS classification for lung adenocarcinoma has been proposed to classify invasive lung adenocarcinoma patients according to the predominant growth pattern present in the tumor: lepidic (LEP), papillary (PAP), acinar (ACN), micropapillary (MPP) and solid (SOL). Several studies have reported consistently that early stage resectable lung adenocarcinoma patients with LEP predominant pattern have a better prognosis, while MPP and SOL predominant patterns have a significantly poorer prognosis. However, the prognostic significance of these histological patterns has not been tested in clinical trials. Furthermore, the clinical utility of this new classification for predicting benefit from adjuvant chemotherapy is unknown.Methods
The representative single H&E slide of 1766 non-small cell lung cancer patients from IALT, JBR.10, CALGB 9633 and ANITA adjuvant chemotherapy trials who participated in the LACE-Bio study were reviewed to confirm the histological diagnosis. These cases were independently assessed by two pathologists involved in the development of this new IASLC/ATS/ERS classification for subtyping. Discordant cases were resolved by consensus. Clinical outcomes were overall survival (OS, main outcome), disease-free survival (DFS) and specific disease-free survival (SDFS) (DFS with censoring deaths not related to cancer). Multivariable Cox models stratified by trial were used for prognostic analyses and the interaction between treatment (chemotherapy / control) and histology subtypes added for predictive analyses. The five histology subtypes were first analysed separately and 3 groups (LEP, PAP+ACN and MPP+SOL) were considered.Results
573 patients were classified as 23 (4%) as LEP, 148 (26%) as ACN, 99 (17%) as PAP, 39 (7%) as MPP and 264 (46%) as SOL. The distribution of histology subtypes was different across trials (p=0.02) but not related with standard prognostic variables. The number of deaths, events and cancer-related events were 269, 320 and 292 respectively. No significant difference was observed between the survival curves of 5 subtypes whatever the endpoint. No prognostic value of 3 histological subtypes was observed for OS (p=0.21 in the control arm) contrary to DFS (p=0.04) and SDFS (p=0.03). These last 2 results were explained by the difference between PAP+ACN and MPP+SOL with hazard ratio (HR)~ACN+PAP vs. MPP+SOL~=0.66 95% confidence interval (CI)=[0.47-0.91] and HR~ACN+PAP vs. MPP+SOL~=0.67 [0.44-0.89] for DFS and SDFS, respectively. Due to the small number of patients with LEP predominant pattern, the predictive value was assessed after excluding this subtype. MPP+SOL patients reported significant DFS benefit from adjuvant chemotherapy (HR=0.58 [0.43-0.80], p<0.001) compared to ACN+PAP patients (HR=1.12 [0.79-1.59], p=0.53; p interaction < 0.01). A similar result was observed for SDFS with HR=0.58 [0.42-0.80], p<0.005 in MPP+SOL compared to HR=1.13 [0.78-1.63], p=0.52 in ACN+PAP (p interaction <0.01) while no predictive effect for OS.Conclusion
Resectable lung adenocarcinoma patients with micropapillary and solid predominant patterns showed a trend for poorer DFS and SDFS compared to patients with the other subtypes, and they show a significantly higher benefit from adjuvant chemotherapy on these outcomes. Histological subtypes according to the IASLC/ATS/ERS classification may be proposed as a stratification factor in design of future adjuvant chemotherapy trials.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 real prognosis of mucinous adenocarcinomas (MAs) diagnosed according to the current IASLC/ATS/ERS lung adenocarcinoma classification is controversial, and in particular, the prognostic value of MA and the relationship among pathologic features, clinicoradiologic presentation, and response to surgical treatment are still unclear. Therefore, the aim of this single-institution retrospective study is to analyze the prognostic role of clinicopathologic and radiologic features in surgically resected MA in a homogenous population of Asian patients.Methods
Analyzed variables are clinicoradiologic presentations, operation type, histologic subtypes, and stage. Univariate and multivariate analyses of survival were performed.Results
From 1994 through 2011, 161 resected lung carcinomas were diagnosed as MA in 158 patients, according to the IASLC/ATS/ERS classification. 158 patients included 114 in 1 stage (72%), 29 in 2 (18%), and 15 in 3 (10%). 117 tumors (73%) were nodular-type and 44 (27%) were consolidation-type. Among 117 nodular MAs, 6 were pure GGO nodules.7 tumors presented as multiple lesions. 4 were AIS (lepidic pattern), 1 was MIA (acinar), and 156 (97%) were invasive adenocarcinoma (147 with acinar and 9 with cribriform pattern). The 5-year recurrence rate was 22%, and the 5-year survival rate was 88%. Five-year OS for patients with nodular type compared with those with consolidation-type was 89 versus 57 % (P < 0.001). Based on the multivariate Cox-proportional analysis, consolidation-type on CT (HR 1.42), cribriform pattern (HR 10.35), higher stage (HR 1.51), and higher SUVmax (HR 1.27) were significant poor prognostic predictor for DFS. As for recurrence, SUV max was the only significant predictor in both multivariate Cox-proportional analysis (HR 1.16, P = 0.016) and the log-rank test (cut-off 4.4, P = 0.045). Figure 1 Figure 2Conclusion
Consolidation-type on CT, cribriform pattern, higher stage, and higher SUVmax would be predictive for lower overall survival. Also, SUVmax would be predictive for higher recurrence and may necessitate more aggressive adjuvant 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.
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O17.03 - Morphological and Mucin profile of lung adenocarcinoma harboring driver mutation (ID 2523)
10:50 - 11:00 | Author(s): N. Motoi, Y. Saito, E. Miyauchi, S. Sato, H. Ninomiya, Y. Ishikawa
- Abstract
- Presentation
Background
Recent advantages of molecular study reveal several subsets of lung adenocarcinoma (AdCa) with specific genetic alterations of receptor tyrosine kinase (RTK), including EGFR, ALK, RET and ROS, which are dramatically responding to targeted inhibitors for activating RTK. The goal of this study is to evaluate the correlation between genetic alteration and histologic phenotype of lung AdCa, including cell type characteristics and mucin phenotype.Methods
319 surgically resected lung Ad CA was examined genetic alterations of EGFR by Cycleave or direct sequencing, ALK by FISH and immunohistochemistry and KRAS by PCR-RFLP and direct sequencing methods. Resected materials were reviewed detail histologic findings, using HE-stained slides of whole tumor. A histologic predominant subtype of AdCa, based on a new IASLC/ATS/ERS classification, and nuclear grading were evaluated. The mucin phenotype of AdCa was evaluated by Immunohistochemical staining, including muc1, muc2, muc5ac and muc6. The correlation between genetic alteration and histologic phenotypes was examined.Results
Genetic alterations of this study were 150 EGFR, 44 ALK, 9 KRAS and 116 wild-type. EGFR mutated AdCa had 55.4% lepidic- (lep), 40% papillary- (pap), 2.6% of acinar- (aci) and 2% of solid- (sol) predominant subtypes. ALK AdCa had 20.5% of lep, 36.4% pap, 18.2% aci, 22.7% sol and 2.3% micropapillary predominant subtypes. Kras mutated AdCa were 44.4% pap, 33.3% aci and 22.2% sol. All wild type AdCa were 35.3% of lep, 53.4% pap, 5.2% aci- and 6% sol. Presence of mucin producing cells was observed in 4.7, 90.9, 66.7, and 26.7% of EGFR, ALK, KRAS and wild type AdCa, respectively. EGFR and ALK showed lower nuclear grade compared to KRAS. IHC examination revealed ALK AdCa was positive for muc1, but negative for muc2, 5ac and 6, in contrast to wild type /EGFR AdCa which were positive for muc1, sometimes for muc2, muc 5ac and/or muc6.Conclusion
In summary, the most common histologic phenotype of EGFR AdCa was lepidic-predominant, non-mucin producing with low nuclear grade; ALK AdCa was papillary, mucin producing with low nuclear grade, and KRAS was papillary, mucin producing with high nuclear grade. The predominant subtype-based classification of AdCa showed an incomplete correlation to a genetic abnormality. Cell type characteristics, including mucin phenotype, would be useful to predict the genetic alteration of lung AdCa, in addition to the predominant subtype which is architecture-based assessment.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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O17.04 - DISCUSSANT (ID 3987)
11:00 - 11:15 | Author(s): M.S. Tsao
- Abstract
- Presentation
Abstract not provided
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O17.05 - Accuracy and Interobserver Agreement in Identifying Histologic Subtypes in Stage I Lung Adenocarcinomas ≤3 cm Using Frozen Section (ID 2590)
11:15 - 11:25 | Author(s): Y. Yeh, J. Nitadori, K. Kadota, A. Yoshizawa, N. Rekhtman, A.L. Moreira, C.S. Sima, V.W. Rusch, P.S. Adusumilli, W.D. Travis
- Abstract
- Presentation
Background
The new IASLC/ATS/ERS classification of lung adenocarcinoma (ADC) histologic subtypes is now recommended for prognostic stratification. The ability to determine histologic subtype accurately by frozen section (FS) may help surgeons to choose limited resection versus anatomic resection in the management of lung ADC. The aim of this study is to investigate the accuracy and interobserver agreement of FS for predicting histologic subtype.Methods
FS and permanent section slides from 361 surgically resected stage I lung ADCs ≤3 cm were reviewed for predominant histologic subtype and presence or absence of lepidic, acinar, papillary, micropapillary, and solid patterns. To determine interobserver agreement, 50 cases were additionally reviewed by 3 pathologists. To test the accuracy of FS in determining degree of invasion in cases with predominantly lepidic growth pattern, 5 pathologists reviewed FS slides from 35 patients and attempted to discriminate between adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant adenocarcinoma (LPA).Results
The accuracy of FS for predicting histologic subtype is shown in the Table. There was moderate agreement on the predominant histologic subtype between FS diagnosis and final diagnosis (κ=0.565). FS had high specificity for micropapillary and solid patterns (94% and 96%, respectively), but sensitivity was low (37% and 69%, respectively). The interobserver agreement was satisfactory (κ > 0.6, except for acinar pattern). All cases of AIS were correctly diagnosed using FS. For MIA, only 41.3% of FS diagnoses were correct, and 52% were overdiagnosed as LPA; for cases of LPA, 79% of FS diagnoses were correct.Parameter Accuracy, % (95% CI) Sensitivity, % (95% CI) Specificity, % (95% CI) κ Predominant histologic subtype Overall 68 (63–73) Not applicable Not applicable 0.565 Lepidic 90 (86–92) 75 (64–84) 93 (90–96) 0.681 Acinar 76 (71-80) 70 (61–77) 79 (73–84) 0.481 Papillary 85 (81-88) 62 (50–72) 91 (87–94) 0.527 Micropapillary 94 (91-96) 21 (9–40) 99 (97–100) 0.277 Solid 91 (88-94) 79 (67–87) 94 (90–96) 0.700 Presence or absence of each histologic pattern Lepidic 80 (76–84) 75 (69–80) 91 (84–96) 0.588 Acinar 89 (85–92) 90 (86–93) 67 (35–90) 0.252 Papillary 72 (67–77) 70 (64–75) 79 (69–87) 0.397 Micropapillary 67 (62–72) 37 (30–45) 94 (89–97) 0.321 Solid 84 (80–88) 69 (61–76) 96 (92–98) 0.670 Conclusion
FS can provide information on the presence of aggressive histologic patterns—micropapillary and solid—with high specificity but low sensitivity. FS is not suitable for determining the predominant pattern or degree of invasion. Although FS can be helpful in diagnosing AIS, it has poor accuracy in distinguishing MIA from LPA.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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O17.06 - Tumor Budding and Nuclear Grade, but not Histologic Subtype, Are Significant Prognostic Factors, Independent of TNM Stage, in Patients with Lung Squamous Cell Carcinoma (ID 2910)
11:25 - 11:35 | Author(s): K. Kadota, J. Nitadori, D.J. Finley, V.W. Rusch, P.S. Adusumilli, W.D. Travis
- Abstract
- Presentation
Background
The new IASLC/ATS/ERS lung adenocarcinoma classification, proposed in 2011, has significant prognostic value. For lung squamous cell carcinoma (SCC), however, no pathologic findings have been widely accepted to predict patient outcomes with the exception of TNM stage. Tumor budding has been recognized as a factor of poor prognosis in colorectal cancer, and nuclear grading has been widely accepted as a prognostic indicator in breast cancer. In this study, we determine whether histologic findings can independently predict prognosis in lung SCC.Methods
All available tumor slides from patients with therapy-naive, surgically resected solitary lung SCC (1999-2009) were reviewed (n=485; stage I/II/III, 281/136/68). Tumors were graded by means of tumor differentiation. Tumors were classified as keratinizing, nonkeratinizing, and basaloid subtypes by presence (≥5%) or absence of keratinization and by predominant (≥50%) basaloid pattern. Tumor budding (tumor nests composed of <5 cells) and presence of single tumor-cell invasion were assessed using 10 high-power fields (HPFs) (x200 magnification) in the areas with the smallest tumor nests. Tumor budding was considered positive when the maximum number of budding was ≥10/HPF. Single tumor-cell invasion was considered positive when it was identified at 10 HPFs. Nuclear diameter was evaluated, at ≥3 HPFs in the largest nuclei, using nearby small lymphocytes as reference and was classified as either large (>4 small lymphocytes) or small (≤4). Overall survival (OS) was estimated using the Kaplan-Meier method, and multivariate analyses were performed using the Cox proportional hazards model.Results
Basaloid subtype correlated with better OS than nonbasaloid subtype (p=0.046). Tumor budding (p<0.001), single tumor-cell invasion (p<0.001), and large nuclei (p=0.005) correlated with worse OS (Table). However, tumor differentiation and presence of keratinization did not correlate with prognosis. The prognostic significance of tumor budding was confirmed in a subgroup analysis limited to stage I (p=0.028) and stage II/III (p=0.008) patients. In addition, basaloid subtype correlated with favorable prognosis (p=0.042), and both single tumor-cell invasion (p=0.014) and large nuclei (p=0.021) were associated with poor prognosis in a subgroup analysis limited to stage I patients. In multivariate analysis, tumor budding (HR=1.04; p=0.024) and large nuclei (HR=1.09; p=0.035) were independent prognostic factors for survival.Table. Overall survival by histologic findings
Histologic finding 5-year OS p Subtype Basaloid 69% (n=33) 0.046 Nonbasaloid 58% (n=452) Tumor budding + 39% (n=76) <0.001 - 62% (n=409) Single cell invasion + 47% (n=197) <0.001 - 67% (n=288) Nuclei Large 50% (n=153) 0.005 Small 63% (n=332) Conclusion
Tumor budding and large nuclei, but not histologic subtype, were significant prognostic factors, independent of TNM stage, for lung SCC. These findings may help to make therapeutic decisions and stratify patients for additional therapy.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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O17.07 - Prevalence, morphology and natural history of FGFR1-amplified lung cancer detected by FISH and SISH (ID 2776)
11:35 - 11:45 | Author(s): P.A. Russell, Y. Yu, R.J. Young, M. Conron, Z. Wainer, B. Solomon, N. Alam, G. Wright
- Abstract
- Presentation
Background
Fibroblast growth factor receptor 1 (FGFR1), which codes for a receptor tyrosine kinase, was recently reported to be amplified in 20% of lung squamous cell carcinoma (SqCC). In vitro and preclinical tests suggest that FGFR1 amplification is a therapeutic target. Our aims were to investigate the prevalence of FGFR1 amplification by fluorescence in situ hybridization (FISH) and determine correlation with outcome in an Australian cohort of resected lung cancer. We also correlated results of FGFR1 FISH with silver in situ hybridization (SISH).Methods
A clinically-annotated tissue microarray was constructed from resected lung cancer tissue collected from 1996-2012. FGFR1 FISH and SISH were performed according to manufacturer’s protocols, with SISH performed on Ventana benchmark XT platform. FGFR1 FISH and SISH were scored by one pathologist, with high level amplification defined as ratio of FGFR1/centromere 8 ≥ 2, or tumor cell percentage with ≥ 15 signals ≥ 10%, or average number of FGFR1 signals/tumor cell nucleus ≥ 6, and low level amplification as tumor cell percentage with ≥ 5 signals ≥ 50%. Results of FGFR1 FISH and SISH were compared. Patient outcome related to FGFR1-amplified tumors was assessed and compared to patients with SqCC, or with a morphologic component of, or immunoprofile of SqCC, but normal FGFR1 copy number.Results
Of 406 tumors tested, there were 191 pure SqCC, 28 carcinomas with a SqCC component, 24 large cell carcinomas with an immunoprofile of SqCC, 115 adenocarcinomas, 22 pulmonary neuroendocrine tumors, and 28 other carcinomas without a morphologic component or immunoprofile of SqCC. FGFR1 amplification was assessable in 368 tumors. FGFR1 amplification was identified with FISH in 50 tumors, 48 (48/225; 21.3%) of which were either pure SqCC or a carcinoma with morphologic component or immunoprofile of SqCC. Only two cases were completely of non-squamous origin (2/143; 1.4%, p<0.00001). FGFR1 SISH was performed in 385 tumors, with 347 tumors assessable. Of 46 FGFR1 FISH-amplified tumors assessed with FGFR1 SISH, all showed FGFR1 amplification with SISH, whilst all other tumors tested were negative. Survival from radically treated FGFR1-amplified tumors was similar to all others with a squamous component (73% versus 60% 5-yr survival, HR 0.68, p=0.25; Figure 1).Figure 1Conclusion
FGFR1 amplification with FISH was identified in 21.3% of pure SqCC or carcinomas with a morphologic component or immunoprofile of SqCC, but only 1.4% of completely non-squamous tumors. All adenocarcinomas and neuroendocrine tumors were negative. FGFR1 SISH showed 1:1 correlation to FGFR1 FISH.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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O17.08 - DISCUSSANT (ID 3988)
11:45 - 12:00 | Author(s): W.A. Cooper
- Abstract
- Presentation
Abstract not provided
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Author of
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MS10 - Beyond Lung Cancer - The Pathology of Intra-Thoracic Mimics (ID 27)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Pathology
- Presentations: 1
- Moderators:G. Chen, Y. Ishikawa
- Coordinates: 10/29/2013, 14:00 - 15:30, Bayside Gallery B, Level 1
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MS10.1 - Metastases to Lung and Differential Diagnosis (ID 501)
14:05 - 14:25 | Author(s): K.F. To
- Abstract
- Presentation
Abstract not provided
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