Prognostic impact of c-MYC and EZH2 expression in small cell and non-small cell lung carcinoma: a single-center retrospective study.

backgroundc-MYC and enhancer of zeste homolog 2 (EZH2) are key regulators of cell proliferation and epigenetic reprogramming and have been implicated in the pathogenesis and progression of lung carcinoma. However, their clinicopathological and prognostic relevance in routine practice remains incompletely defined. This study aimed to evaluate the relationships between c-MYC and EZH2 immunohistochemical expression and survival in patients with small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC).

methodsThis single-center retrospective study included 131 patients (98 NSCLC, 33 SCLC) followed at the outpatient clinic of medical oncology department with available archival formalin-fixed, paraffin-embedded tumor tissue. c-MYC and EZH2 expression was assessed immunohistochemically in tumor samples and evaluated by nuclear staining intensity and the percentage of stained tumor cells. For survival analyses, marker expression was dichotomized using a 30% cut-off of the percentage of stained tumor cells, and clinicopathological features were compared between groups. Overall survival (OS) was estimated using the Kaplan–Meier method and compared by the log-rank test. Prognostic factors for OS were examined using multivariate Cox proportional hazards models.

resultsHigh c-MYC expression was associated with worse OS and an independent adverse prognostic factor in multivariate Cox regression [hazard ratio (HR) 1.86, 95% confidence interval (CI) 1.11–3.13; p = 0.019], together with poor performance status (ECOG ≥ 2; HR 2.91, 95% CI 1.73–4.89; p < 0.001). In contrast, EZH2 expression, although frequently positive and modestly correlated with c-MYC, was not significantly associated with OS.

conclusionIn this retrospective cohort of lung carcinoma patients, high c-MYC expression, but not EZH2 expression, was independently associated with poor OS after adjustment for clinical factors. c-MYC immunohistochemistry may provide additional prognostic information beyond conventional clinicopathological parameters. Larger prospective studies with standardized scoring systems are warranted to validate these findings and to clarify the clinical utility of c-MYC and EZH2 as potential prognostic and therapeutic biomarkers in lung cancer.