Clinical significance of MYC family protein expression in surgically resected high-grade neuroendocrine carcinoma of the lung.

Abstract

MYC family genes including MYC, MYCN, and MYCL are amplified and overexpressed as oncogenic drivers in high-grade neuroendocrine carcinoma of the lung (HGNEC), but little is known about their clinical significance. This study evaluated the prognostic impact of MYC family protein expression in patients with surgically resected HGNEC. Immunohistochemical analyses were performed on 83 resected specimens of HGNEC using antibodies against MYC family proteins (c-MYC, n-MYC, and l-MYC). When nuclear staining of any intensity in ≥10% of tumor cells showed immunoreactivity with any one or more of c-MYC, n-MYC, or l-MYC, the specimens were defined as MYC family-positive. A total of 83 patients were analyzed. MYC family-positive status was observed in 33.7% (28 of 83 cases) and was not correlated with clinicopathological factors. The protein expression was mutually exclusive and no duplicate cases were observed. A log-rank test showed that MYC family-positive status was significantly associated with shorter overall survival (OS) (p=0.003) and recurrence-free survival (RFS) (p=0.039). According to Cox multivariate analysis, MYC family-positive status had a significant effect on shorter OS (hazard ratio [HR]=2.217, 95% confidence interval [CI] 1.179-4.169, p=0.014) and RFS (HR=1.802, 95% CI 1.014-3.202, p=0.045). In patients with pathological stage I, MYC family-positive status also showed significantly poor OS (HR=2.847, 95% CI 1.236-6.557, p=0.014) and RFS (HR=2.088, 95% CI 1.006-4.332, p=0.048) in the multivariate analysis. MYC family protein expression could be an independent unfavorable prognostic factor in patients with surgically resected HGNEC.