Immunohistochemistry of p53 surrogates mutation as an accurate predictor for early-relapse of surgically resected stage I-III lung adenocarcinoma.

INTRODUCTION

is a strong tumor suppressor gene; its deactivation contributes to carcinogenesis and influences clinical outcomes. However, the prognostic influence of p53 deactivation on early relapse in patients with surgically resected non-small cell lung cancer remains unclear.

MATERIALS AND METHODS

A cohort of 170 patients with primary stage I through III lung adenocarcinoma (LADC) and lung squamous cell carcinoma who underwent complete resection at Tokyo Medical and Dental University was screened for mutations using panel testing, and association studies between mutations and clinical data, including histology and postoperative recurrence, were performed. The association between mutations and postoperative recurrence was validated using data from 604 patients with MSK-IMPACT from The Cancer Genome Atlas. Additional immunohistochemistry for p53 was performed on some subsets of the Tokyo Medical and Dental University population.

RESULTS

Mutations in were recurrently observed (35.9%; 61 out of 170) in the Tokyo Medical and Dental University cohort. In the histology-stratified analysis, patients with LADC histology showed mutations that were associated with poor relapse-free survival (log-rank test;  = .020), whereas patients with lung squamous cell carcinoma histology showed mutations that were not ( = .99). The poor prognosis of mutation-positive LADCs was validated in The Cancer Genome Atlas-LADC cohort (log-rank test;  = .0065). Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between mutations and abnormal IHC pattern of p53 (Cramer's correlation coefficient  = 0.67).

CONCLUSIONS

mutation is a potential marker for worse prognosis in surgically resected LADC; immunohistochemistry for p53 could be a surrogate method to identify patients with LADC with a worse prognosis.