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M. Oomasa
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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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P1.04-014 - Clinicopathologic Significance of Epithelio-Mesenchymal Transition in Human Lung Adenocarcinoma (ID 2321)
09:30 - 09:30 | Author(s): M. Oomasa
- Abstract
Background:
Activation of Epithelial-Mesenchymal Transition (EMT) mechanisms in tumor cells is known to be associated with its invasive and metastatic properties. However, this hypothesis has not been fully elucidated from the point of detailed clinicopathological view using surgically resected clinical samples. We, hereby, examined the expression levels of EMT marker and analyzed the integrated data of clinicopathlogical information including background genetic alterations.
Methods:
Clinical samples were obtained from the 256 cases of resected lung adenocarcinoma which were consecutively operated from January 2001 to December 2007 in Kyoto University Hospital. Pathological stage distribution of the cases by TNM classification (WHO, 7th edition) was below: 1A: 132, 1B: 56, 2A: 22, 2B: 4, 3A: 26, 3B: 2, 4:14. Mean survival time of all the cases was 62 months, and 5-year survival rate was 75.3%. The distribution of predominant histlogical subtype by IASLC/ATS/ERS classification was AIS (9, 3.5 %), MIA (13, 5.1 %), lepidic (18, 7.0 %), acinar （32, 12.5 %）, papillary (122, 47.6%), solid (44, 17.2 %), micropapillary (9, 3.5 %), mucinous (8, 3.1 %), others (1, 0.4 %). We performed immunohistochemical staining for the expression of E-cadherin and Vimentin on tissue microarrays of resected samples to assess the activation level of EMT. Then, we classified the cases with positive E-cadherin expression and negative for Vimentin as “null” activation of EMT mechanisms, called ‘Group N’, whereas loss of E-cadherin and positive for Vimentin as “full” activation, ‘Group F’, and, further, either loss of E-cadherin or positive Vimentin as “partial” activation, ‘Group P’. DNA samples were extracted from frozen surgical samples and the mutations for the hot-spot exons of EGFR, ALK, K-ras, and p53 were detected by SSCP or direct sequencing methods. Statistical analyses for survival were performed by Kaplan-Meirer curve and log-rank test. Categorical data were analyzed by Pearson’s test. P-values < 0.05 were considered to be statistically significant.
Results:
Histological subtypes were significantly associated with EMT activation level. Poorly differentiated tumors mainly comprising solid, micropapillary, and mucinous adenocarcinoma possessed highly activated EMT level, and vice versa. Group F showed the highest positivity both in local lymphatic/vascular invasion and lymph-node metastasis (35.7%/ 42.9%/ 46.3%, respectively), followed by group P and group N in order. Significant difference was found in 5-year disease-free/ overall survival rate among these 3 groups: group F, 46.9%/ 50.6%; group P, 64.9%/ 73.4%; group N, 74.9%/ 85.4%. Tumors harboring wild type EGFR or mutant p53 had tendency to acquire higher EMT activation level. Interestingly, p53 mutation rate significantly correlated with EMT activation level especially in mutant EGFR tumors, whereas no correlation in wild type EGFR ones. No significant correlation was shown between EMT activation level and the proportion of K-ras mutation or ALK fusion gene.
Conclusion:
Our results revealed that the activation of EMT mechanisms in human lung adenocarcinoma is significantly associated with histological subtypes and plays important roles in the tumor progression through its lymph-vascular local involvement leading to the node-metastasis. Among human lung adenocarcinomas harboring EGFR mutation, p53 alteration deeply correlates with EMT activation.
