P66.02 The Prognostic Implication of hes1 Protein Expression in Resected Small Cell Lung Cancers of 247 Cases

Abstract

Small cell lung cancer (SCLC) is a highly aggressive malignancy prone to early recurrence and metastasis. Preclinical studies have found that Hes1, as a transcription repressor of the basic helix-loop-helix (BHLH) family, can not only prevent the proliferation and migration of SCLC tumor cells, but also inhibit the neuroendocrine transcription factor ASCL1. However, the prognostic implication of Hes1 protein on surgically resected SCLCs remains unclear. The current study aims to analyze the expression pattern and prognostic value of Hes1 protein in SCLC. Two hundred and forty seven surgically resected pure SCLC specimens were reviewed and included in this study by using tissue microarrays (TMA) for immunohistochemistry（IHC）analysis of Hes1 protein on a fully automatic Roche immunohistochemical instruments . And the corresponding clinicopathological features such as age, lymph node metastasis, major cell shape and tumor infiltrating lymphocytes(TILs), etc were reviewed and collected. Correlation analysis of Hes1 protein with clinic pathological features and survival analysis was performed using SPSS 25.0 and Graphpad Prism 5.0. Among the 247 surgically resected pure SCLC patients, 175 (71%) were male and 202 (82%) were less than 65 years. According to the AJCC Cancer Staging Manual (seventh edition), 78 (31.6%) were stage I, 68 (27.5%) were stage II, and 101 (40.9%) were stage III. Hes1 expression was localized in the nucleus of SCLC tumor cells. A total of 129 of the 247 enrolled SCLC patients showed high expression of Hes1 with a positive rate of 52.2%(129/247), and was found positively correlated with a lower age(≤65 yrs., p=0.014), no lymph node metastasis(P=0.003), main cell morphology of round cells(p=0.002), and TILs≤30% (p=0.010). Univariate survival analysis revealed a favorable survival in high expression group for a significant disease free survival (DFS, HR=1.477,95%CI 1.025-2.129, P=0.036 ) and a positive trend of overall survival (OS, HR=1.181,95%CI 0.778-1.792,P=0.435). In limited stage pure small cell lung cancer, high expression of Hes1 protein is related to age, lymph node metastasis, main cell morphology and TILs , which contributes as a potential biomarker for the prognosis of SCLC patients.