The prognostic role of c-kit protein expression in resected large cell neuroendocrine carcinoma of the lung

Background. Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor of the lung that shares some clinicopathologic and molecular features with small cell lung carcinoma (SCLC). Optimal treatment has not yet been standardized and significant prognostic factors are lacking. Because c-kit protein overexpression has been recently reported as a negative prognostic factor in SCLC we investigated its expression and prognostic value in a series of LCNEC. Methods. Resected LCNEC fulfilling the morphologic criteria of the 1999 World Health Organization classification of lung tumors and showing neuroendocrine differentiation by appropriate immunohistochemical markers were retrospectively reviewed. Immunostaining for c-kit protein expression was performed using the polyclonal antibody CD117. Clinical and pathologic characteristic were reported and analyzed and a survival study was performed. Results. Thirty-three patients underwent radical resection. Thirty-one were male (94%) and 32 were smokers (97%). Ten (30.3%), 11 (33.3%), 5 (15.2%), and 7 (21.2%) were at stage IA, IIB, IIB, and IIIA respectively. Overall 1-, 3-, and 5-year survival rates were respectively 79%, 58%, and 51%. Survival analysis showed no differences for any of the clinicopathological features except for CD117 immunostaining: 1-year and 3-year survival rates were respectively 91% and 82% for CD117-negative LCNEC, and 72% and 44% for CD117-positive ones (p=0.046). Positivity of CD117 was significantly related to recurrence rate: 60% versus 23% for CD117 positive and negative LCNEC respectively (p=0.037). Conclusions. Radical resection of large cell neuroendocrine carcinoma achieves poor outcomes. The c-kit protein is frequently expressed in this neoplasia and its expression represents a negative prognostic factor. This immunohistochemical marker may represent the basic rationale to select LCNEC for novel targeted therapy.