Clinicopathological significance of cyclooxygenase-2 and cell cycle-regulatory proteins expression in patients with esophageal squamous cell carcinoma

Abstract

The aim of this study was to examine the expression of the molecular markers cyclooxygenase-2 (COX-2), Ki-67, cyclin A, and p27 in patients with esophageal squamous cell carcinoma (ESCC), to ascertain the relationship of these makers with the clinicopathological significance of the patients, and to assess the additional prognostic value of the expression profile of these proteins for ESCC patients. The expression levels of COX-2, Ki-67, cyclin A, and p27 proteins of a series of primarily resected ESCC samples were determined by immunohistochemistry method. Clinicopathological and molecular factors affecting survival were analyzed by multivariate analysis. A total of 78 specimens were included in this study. Expression of COX-2 was observed in 43 (55.1%) cases, and high levels of expression of Ki-67, p27, and cyclin A were observed in 57 (73.0%), 33 (42.3%), 43 (55.1%) cases, respectively. The results of univariate survival analysis indicated that more advanced tumor stage, lymph node involvement, systemic dissemination, the levels of expression of COX-2, Ki-67, cyclin A, and p27 were associated with survival (all P-value < 0.05). Multifactorial survival analysis revealed that only lymph node involvement, over-expression of cyclin A, and low p27 expression were associated with the survival of the patients (hazard ratios = 2.83, 4.7, 2.9, respectively; P= 0.025, 0.042, 0.005, respectively). Among the molecular markers assessed, the expression of cell proliferation markers cyclin A and p27 are independent prognostic factors in patients with ESCC, whereas neither COX-2 nor Ki-67 is of independent prognostic value.