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Y. Yeh

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-008 - Expression of Mismatch Repair Proteins Associates with Survival and Response to EGFR Tyrosine Kinase Inhibitors in Lung Adenocarcinoma Patients (ID 9167)

      09:30 - 16:00  |  Author(s): Y. Yeh

      • Abstract

      Mismatch repair (MMR) pathway is a fundamental cellular process required for the maintenance of genomic stability. Recently, a growing body of evidence suggests that a non-canonical MMR (ncMMR) function may be present as a source of mutations in human cells, which could lead to tumorigenesis. The dual functions of MMR with anti-mutagenic and mutagenic activities complicate its role in disease. Given that the functional role of MMR in lung cancer was rarely reported and is still controversial, the current study aimed to address the clinical significance of MMR proteins and their associations with therapeutic biomarkers in lung adenocarcinoma.

      A panel of tissue microarrays containing 442 lung adenocarcinomas was examined for the expression of MMR proteins MLH1, PMS2, MSH2 and MSH6 using immunohistochemistry. The associations between MMR expression and clinicopathological features, patients’ survival as well as therapeutic biomarkers including EGFR mutation and PD-L1 expression were analyzed.

      MLH1, PMS2, MSH2 and MSH6 protein expression significantly correlated with one another in lung adenocarcinoma (p<0.001). Neither age nor sex nor predominant histological pattern correlated with their expression, except that only MSH2 expression positively associated with the solid-pattern growth (p<0.05). Survival analyses showed that high expression of each MMR protein statistically correlated with poor patients’ overall and progression-free survivals (p<0.05). For therapeutic biomarker analysis, expression of MMR or PD-L1 independently associated with poor patients’ overall survival, but no significant correlation between their expression was observed. High expression of MLH1, MSH2 and MSH6 (p<0.05) but not PMS2 (p=0.12) was linked to poor survival in EGFR mutation-positive patients. To examine EGFR-TKI treatment response, the outcomes of 50 patients with EGFR mutation-positive tumors treated with EGFR-TKI were included for further analysis. Interestingly, patients with high expression of MLH1 in tumors showed a worse progression-free survival after EGFR-TKI treatment (n = 23, 13.8 months, 95% CI: 6.5 to 21.1 months) than those with low expression (n =27, 25.6 months, 95% CI: 10.9 to 40.3 months).

      MMR proteins are overexpressed in lung adenocarcinoma and significantly associate with poor patients’ survival, which may have a prognostic value in predicting patients’ drug response and clinical outcomes. Our results also raise a possibility that ncMMR function may participate in the tumorigenesis of lung adenocarcinoma.