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Jin-Haeng Chung
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MS 18 - Biomarker for Anti-PD-L1 Therapy (ID 540)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yuichi Ishikawa, Sanja Dacic
- Coordinates: 10/17/2017, 15:45 - 17:30, Main Hall
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MS 18.04 - PD-L1 Expression in Early Stage Lung Cancer (ID 7646)
16:30 - 16:45 | Presenting Author(s): Jin-Haeng Chung
- Abstract
- Presentation
Abstract:
The significant activity of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors in heavily pre-treated patients with advanced non–small-cell lung cancer (NSCLC) marked the beginning of a new era of immunotherapy. Recently published randomised clinical trials’ data have led to the approval of 3 PD-1/PD-L1 inhibitors—nivolumab (Opdivo; Bristol-Myers Squibb Company), pembrolizumab (Keytruda; Merck Sharp & Dohme Corp), and atezolizumab (Tecentriq, Genentech/Roche)—for the treatment of advanced NSCLC after first-line therapy. Furthermore, pembrolizumab was recently approved by the FDA as a first-line therapy for patients with advanced NSCLC. However, the overall response rates to these agents in an unselected population are reportedly low, thus emphasising the need for predictive biomarkers that identify beneficial candidates. The recently approved tests for anti-PD-1/PD-L1 therapy in NSCLC include the assessment of PD-L1 expression using immunohistochemistry (IHC) as a companion diagnostic test (22C3 for pembrolizumab) and 2 complementary diagnostic tests (28-8 for nivolumab and SP142 for atezolizumab). Another PD-L1 assay is being currently tested in clinical trials (e.g. SP263). In addition to commercial assays, laboratories and research institutions may establish their own laboratory-developed tests (LDTs) using various antibodies available, most notably the E1L3N clone. Hence, the PD-L1 expression status, as well as its predictive and prognostic value, differ considerably based on the antibody clones, platforms, and interpretation criteria used. However, the current assays evaluating the predictive role of tumour PD-L1 expression remain without harmonization in terms of the staining analysis and scoring system. The intratumoural heterogeneity in PD-L1 expression is another important issue. At present, PD-L1 testing is mainly conducted on biopsy specimens, which may not represent the tumour as a whole, and it may lead to false results, particularly in cases where testing is conducted using small tissue specimens, such as bronchial or transthoracic biopsy specimens. The resulting false-negative results could lead to the under-treatment of patients. In this presentation, I’d like to introduce 1) the results of comparison study between 4 different PD-L1 IHC and scoring systems in the surgically resected early stage lung cancer specimen 2) the correlation of PD-L1 expression between TMA specimens and the corresponding resected specimen to better understand the intratumoral heterogeneity.
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-027 - Minute Pulmonary Meningothelial-Like Nodules Presenting as Multiple Ground-Glass Density Nodules (GGNs): A Case Report (ID 8960)
09:30 - 09:30 | Author(s): Jin-Haeng Chung
- Abstract
Background:
Minute pulmonary meningothelial-like nodules (MPMNs) are generally detected incidentally in resected lung specimens. Recently, with increased use of high-resolution computer tomography (HRCT), MPMNs have occasionally been detected before surgery. They may appear as mild restrictive lung disease or randomly distributed micronodules of ground-glass attenuation on HRCT.
Method:
In this study, we retrospectively evaluated a case in which multiple ground glass density nodules (GGNs) were detected incidentally and operated for diagnosis in our hospital with the final diagnosis of MPMNs.
Result:
A 58-year-old non-smoking woman was referred to our hospital for multiple GGNs in bilateral lower lobes detected on a chest CT scan. HRCT was obtained for further evaluation. Numerous tiny GGNs were seen in the both lower lungs with centrilobular, subpleural and gravitational distribution. Many of them showed cystic or cavitary changes. Three differential diagnoses were presented by HRCT findings. The first was multifocal adenocarcinoma in situ or adenocarcinoma, the second was multifocal micronodular pneumocyte hyperplasia, and the third was atypical manifestation of langerhans cell histiocytosis or respiratory bronchiolitis interstitial lung disease. A follow up HRCT was reobtained after 2 months to determine diagnostic strategy and there was no significant change or mild prominence. For pathologic confirmation, video-assisted thoracoscopic surgery (VATS) right lower lobe wedge resection was performed. Microscopically, the surgical lung biopsy specimen showed multifocal ovoid cell proliferation along alveolar interstitium. The cells were bland, and no mitotic activity was identified. Immunohistochemical analysis was performed, and the sample was positive for epithelial membrane antigen (EMA), progesterone (PR) and CD56. Cytokerain, thyroid transcription factor-1, and S100 were negative. Finally the diagnosis of MPMNs was established, and there was no evidence of malignancy. On the second postoperative day, the patient was discharged without any complications.
Conclusion:
MPMNs are not uncommon incidental pathologic findings but the HRCT findings are nonspecific. They can occasionally manifest as multiple GGNs on HRCT, mimicking multifocal adenocarcinoma in situ or interstitial lung disease. Although most cases do not require special treatment, when there is no confident clinical diagnosis, such as in our case, a pathological correlation could be performed. An awareness of MPMNs presenting as GGNs is important because it may simulate neoplastic or other nonneoplastic diseases.
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P1.02-029 - Pulmonary Adenofibroma with Cystic Change: A Case Report (ID 9195)
09:30 - 09:30 | Author(s): Jin-Haeng Chung
- Abstract
Background:
Pulmonary adenofibroma is a rare benign tumor with biphasic pattern resembling adenofibroma of female genital tract and fibroepithelial lesion of breast. Since Scarff and Gowar first described it as a fibroadenoma of lung in 1944, only 10 cases have been reported in English literature. It is generally detected in middle-aged patients with solitary subpleural nodule. Histogenesis of this lesion is controversial, whether it is hamartomatous lesion or benign neoplasm. We report a case of a pulmonary adenofibroma in a 77-year-old male, presented with a subpleural bulla.
Method:
Section not applicable
Result:
A 77-year-old male, an ex-smoker, presented with chronic cough. Chest computed tomography revealed a 7-cm sized bulla in right middle lobe. As the large bulla had a thick wall and increased with lapse of time, resection was done. Frozen diagnosis suggested a proliferative lesion which cannot exclude mesothelioma or a parenchymal epithelial neoplasm. Grossly, the tumor was subpleural cystic lesion with central solid portion. Histologically, the lesion was characterized by a leaf-like branching and glandular pattern composed of a single layer of bland ciliated cuboidal lining epithelium and fibrous stroma. Immunohistochemical analysis revealed epithelium that stained positively for cytokeratin 7 and TTF-1, and stroma stained positively for SMA and nonspecific for CD34. The patient was diagnosed as pulmonary adenofibroma and discharged without any complications.
Conclusion:
Pulmonary adenofibroma is a rare biphasic tumor that could be misinterpreted as other benign or malignant tumors. Pulmonary hamartoma and solitary fibrous tumor could contain entrapped bronchial epithelium in the periphery of the tumor, which is distinguished from diffusely distributed epithelial component of adenofibroma. Pulmonary blastoma is another biphasic tumor which has a distinctive primitive appearance of epithelial and mesenchymal components. Moreover, this case presented as a thick-walled bulla that the possibility of primary mucinous adenocarcinoma or cystic metastasis was suspected in the radiological examination. Although pulmonary adenofibroma is recommended minimal surgical resection, lobectomy was done in this case due to its diagnostic difficulty in radiology and intraoperative frozen pathology. To avoid any inappropriate treatment, pulmonary adenofibroma should be regarded as a differential diagnosis of a solitary pulmonary nodule showing biphasic appearance.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-016 - Correlation of Programmed Cell Death Ligand-1 Messenger RNA and Protein Expression in Non-Small Cell Lung Cancer (ID 9472)
09:30 - 09:30 | Author(s): Jin-Haeng Chung
- Abstract
Background:
Monoclonal antibodies targeting the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have been showing promising results in advanced non-small cell lung cancer (NSCLC). Here, we investigated PD-L1 messenger RNA (mRNA) expression by a novel RNA in situ hybridization technique and compared it with PD-L1 protein expression in NSCLC.
Method:
Primary NSCLC specimens of 687 patients (476 adenocarcinoma and 211 squamous cell carcinoma) were constructed into tissue microarrays. PD-L1 mRNA in situ hybridization was performed with RNAscope[®] assay and classified using two independent scoring systems (RNA scope score and RNA proportion score). We also performed immunohistochmisty (IHC) using the Dako 22C3 pharmDx assay for evaluating PD-L1 protein expression.
Result:
PD-L1 mRNA expression was detected in 11.9% by RNA scope score and 8.3% by RNA proportion score. PD-L1 protein expression showed a positivity of 25.2% for the 1% cut-off, and 9.9% for the 50% cut-off. The two RNA scoring systems showed a linear correlation to each other (r = 0.83, p < 0.01), as well as to PD-L1 IHC repectively (p < 0.0001). The cut-off value that best correlated with PD-L1 protein expression was “1” for both RNA scope score (κ = 0.43 for the 1% and 0.58 for the 50% IHC cut-off) and RNA proportion score(κ = 0.36 for the 1% and 0.60 for the 50% IHC cut-off). Applying this criteria, discordant cases were found in 20% and 9% with 1% and 50% IHC cut-offs, respectively.
Conclusion:
PD-L1 mRNA expression, evaluated either as RNA scope score or as RNA proportion score, showed promising statistical results in predicting PD-L1 protein levels. We could thereby set out the RNA scoring system for PD-L1 in NSCLC. Discordant cases with positive mRNA levels and negative immunohistochemical results may indicate that PD-L1 mRNA in situ hybridization could be a more sensitive marker than immunohistochemistry. To verify the predictive role of PD-L1 mRNA expression in immunotherapy, however, therapeutic response to anti-PD-1/PD-L1 inhibitors should be investigated in future studies.
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P3.02-017 - Apoptosis-Related Protein in Non Small Cell Lung Cancer: Correlation of Clinicopathologic, Molecular Characteristics and Prognosis (ID 10011)
09:30 - 09:30 | Author(s): Jin-Haeng Chung
- Abstract
Background:
The role of apoptosis protein that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate the expression of apoptosis-related protein (survivin and bcl-2 family) and to identify their association with the clinicopathologic parameters and prognosis of patients with NSCLC.
Method:
Immunohistochemical (IHC) staining of pro-apoptotic (bax, bad, bim), anti-apoptotic proteins (bcl-2, survivin) and proliferation marker (Ki-67) was performed on tissue microarray sections from tumor tissues of 373 NSCLCs. Correlations between the expression of the above proteins and clinicopathologic, molecular features (EGFR mutation, KRAS mutation, ALK translocation and MET amplification) and prognostic significance were analyzed.
Result:
Analysis of the two main subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) individually showed that different markers were significant in the different subtypes. The expression of survivin, bax and Ki-67 was significantly different in ADC and SCC. In ADC, the increased expression of survivin was associated with the presence of vascular invasion, lymph node metastasis and tumor recurrences, but we did not find any correlation with survivin expression and clinicopathological parameters in SCC. The increased expression of bax was associated with the presence of lymphatic invasion and tumor recurrence in SCC, but no correlation with bax expression and clinicopathological parameters was observed in ADC. Kaplan–Meier survival analysis showed that survivin and Ki-67 were significant prognostic markers for ADC, whereas bax was a significant prognostic marker for SCC. Patients with high survivin and Ki-67 expression had significantly shorter disease-free survival as well as shorter overall survival than those with low survivin and Ki-67 expression. In SCC, patients with high bax expression had significantly shorter disease-free survival than those with low bax expression. Multivariate Cox analysis confirmed that survivin, Ki-67 and bax were independent prognostic factors in ADC and SCC, respectively. Among the six markers, only high bim expression was significantly related with the presence of MET amplification (p = 0.025), however, other five markers lack significant associations with EGFR, KRAS, ALK, MET gene status.
Conclusion:
Our results suggest that survivin and Ki-67 are independent negative prognostic factors in ADC and bax is an independent negative prognostic factor in SCC. Testing for these markers will help to determine the clinical relevance of NSCLC. Bim may possibly play a role in MET-amplified lung cancer.
