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Y. Ishikawa
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-021 - No MAML2 Gene Alteration Found in Ciliated Muconodular Papillary Tumor of Lung; Genetic Difference from Mucoepidermoid Carcinoma (ID 490)
09:30 - 17:00 | Author(s): Y. Ishikawa
- Abstract
Background:
MAML2 (mastermind-like 2 (Drosophila)) gene, a transcriptional coactivator for NOTCH proteins, is known to be involved as a part of fusion gene (MECT1-MAML2) which is found in mucoepidermoid carcinoma (MEC) both of salivary gland and pulmonary origin. Ciliated muconodular papillary tumor (CMPT) is sharing morphologic features with mucoepidermoid carcinoma, at least in part, i.e. consist of mixture of mucinous and squamous epithelium. To determine whether these morphological mimics can share the molecular alterations, we evaluated MAML2 rearrangement of CMPT by FISH.
Methods:
Five cases of CMPT was recruited from pathologic diagnostic records between 2005 to 2014. Morphological assessment was done on routine HE stained slides of whole tumor specimen. Representative area was selected and submitted to FISH analysis. Fluorescence in situ hybridization (FISH) using break apart type MAML2 gene probes was performed on FFPE specimen. The break apart signal percentages on separated tumor nuclei was counted on the captured images of digital fluorescence microscope. 100 nuclei was counted in each cases. More than 30% of break apart signal is considered as positive result.
Results:
All five CMPTs were reviewed and confirmed the diagnosis on HE stained slides. These cases included 4 male, 1 female, were mean age of 71 years-old (range 60-83). There were three incidental cases which were patients with one primary lung adenosquamous carcinoma and two metastatic cancer (one colon cancer, one liposarcoma). All of five CMPT resulted negative for MAML2 break-apart FISH.
Conclusion:
These results indicated that CMPTs do not share the molecular alteration of MAML2, which is commonly detected in mucoepidermoid carcinoma of lung. In conclusion, CMPT is a distinct tumor or tumor-like lesion, does not related to MEC. Although, it is still uncertain whether CMPT is a true neoplastic lesion with multi-lineage differentiation potential or a reactive process with extensive epithelial proliferation.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-072 - Immunohistochemical PDL1 Expression and Clinicopathological Characteristics in 541 Surgically Resected Non-Small Cell Lung Cancers (ID 2737)
09:30 - 17:00 | Author(s): Y. Ishikawa
- Abstract
Background:
Immune-checkpoint therapy targeting programmed cell death protein 1 (PD1) and programmed cell death protein ligand1 (PD-L1, PDL1, CD274) has been emerging as a new therapeutic strategy for patients with cancer. PDL1 binding to PD1 expressing on the surface of T-cell suppresses activation and proliferation of T-cell. Many types of cancer frequently overexpress PDL1 and escape the immune system. PDL1 expression of tumors may be a useful marker of responsibility for the immune-checkpoint therapy targeting for PDL1. However, the incidence of PDL1 positive cases and related patients’ characteristics among NSCLC is still unclear. The aim of this study is to clarify these unsolved questions.
Methods:
The 541 surgically resected non-small cell lung cancers (NSCLC) between 1994 and 2014 were recruited as following criteria; including primary lung cancer, excluding pathological incomplete resection, limited resection, in-situ carcinoma, small-sized carcinoma, large cell neuroendocrine carcinoma, pleomorphic carcinoma, synchronous or metachronous multiple cancer and metastatic cancer. Tissue microarrays (TMA) were constructed using formalin-fixed paraffin embedded (FFPE) tumor specimen of each representative histologic area. Patients’ characteristics and outcomes were collected from medical chart. The PDL1 expression was evaluated by immunohistochemistry (IHC) using anti-CD274 (PDL1) antibody (Clone ERP1161 (2), Abcam) as primary antibody on 4-micrometer-thick TMA specimen by an auto-staining machine. The results of IHC were evaluated by microscopy and scored with a combination of intensity and proportion. The intensity was defined as negative: 0, weakly positive: 1+, strongly positive: 2+), the proportion was defined positive cell percentage with 10% increments. Based on PDL1 score defined as ∑ [intensity (0, 1, 2) x proportion of each intensity], the tumors were divided as PDL1 positive group (score >50) and PDL1 negative group (score ≤50). We compared between two groups in clinicopathological characteristics and prognosis.
Results:
541 NSCLCs were classified into PDL1 positive (n = 171, 32%) and negative group (n = 370, 68%). The PDL1 positive group was significantly less differentiated (p < 0.001), higher rate of lymphatic (p = 0.010), vascular invasion (p = 0.036), lymph node metastasis (pN1-3) (p = 0.012), and advanced pStage (p = 0.002) compared to negative group. There were no significant differences in sex, age, smoking habit, tumor size, pT factor, and distribution of histological types between two groups. Although the prognostic analysis showed no difference between PDL1 positive vs negative groups (p = 0.861), the histology-based stratification analysis revealed that PDL1 positive squamous cell carcinoma (SqCC, n=28) showed better overall survival rate compared to PDL1-negative SqCC (n=53) (p = 0.018).
Conclusion:
Our data indicated that the PDL1 positive NSCLCs had worse pathological factors, including tumor differentiation, lymphovascular invasion, pN, and pStage, but did not show a statistically significant difference in terms of overall survival rate compared to PDL1-negative group. It is of interest that PDL1 positive SqCC showed a better prognosis than PDL1 negative SqCC.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-024 - Lung Adenocarcinoma with Neuroendocrine Feature Revealed by Transcriptome Profiling (ID 881)
09:30 - 17:00 | Author(s): Y. Ishikawa
- Abstract
Background:
Although our previous transcriptomic analyses revealed that a subgroup in lung adenocarcinoma with a neuroendocrine feature exhibits poor prognosis, the link of the phenotype with patient outcomes has been limited only to two populations derived from a Japanese and a US institution. Here we performed additional transcriptomic profiling analyses to elucidate whether our method was useful also to other populations.
Methods:
Seven independent web-based datasets of lung adenocarcinoma, either on expression microarrays or on an RNA-seq platform, were examined. The expression level of the ASCL1 geneset (100 probes closely correlated with ASCL1 expression) was used to define the neuroendocrine character based on the method we previously reported. Subtyping was performed by consensus clustering with non-negative matrix factorization. Correlation of overall survival was analyzed with the Kaplan-Meier method.
Results:
The neuroendocrine subtype was identified from each of seven independent cohorts with 45, 90, 117, 183,196, 443 and 548 lung adenocarcinoma samples. Among them, three datasets showed statistically significant association with patient survival (p<0.05). The neuroendocrine subtype was inversely correlated with expression of ubiquitination genes. Somatic mutations identified in the neuroendocrine subtype with the TCGA data were common ones such as TP53, STK11 and KRAS.
Conclusion:
Transcriptomic profiling partially reproduced the neuroendocrine subtype in lung adenocarcinoma samples derived from the independent datasets.
