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.

Odontogenic epithelial proliferation is correlated with COX-2 expression in dentigerous cyst and ameloblastoma

“…The current study results demonstrated that proliferation activity and COX-2 expression were positively correlated in the odontogenic epithelium of dentigerous cyst and ameloblastoma, respectively. These results are in accordance with other studies that revealed such a correlation in other different tumor types, for example, in mucosa-associated lymphoid tissue lymphoma (20), colorectal adenoma (19), cervical adenocarcinomas (12), renal cell carcinoma (18), esophageal adenocarcinoma (21), and esophageal squamous cell carcinoma (22). It has been shown that COX-2 may play a role in different steps of tumor progression by increasing the proliferation of mutated cells, thus, favoring tumor promotion (17).…”

“…COX-2 may play a role in different steps of tumor progression by increasing the proliferation of mutated cells (17). Previous studies have shown that COX-2 has a positive correlation with the expression of Ki-67 proteins in various types of tumor (12,(18)(19)(20)(21)(22).…”

The prognostic value of cyclooxygenase-2 expression in patients with esophageal cancer: evidence from a meta-analysis

“…Four studies evaluated only clinico-pathological parameters,8,24,31,33 5 studies evaluated only OS,8,11,18,20,21 and the remaining 16 studies investigated both clinicopathological parameters and OS 6,7,9,10,12–17,19,22,23,32–36. Eighteen studies were conducted on Asian patients,6,9–13,16,18,19,21–24,31,33–36 and 7 studies were conducted on Caucasian patients 7,8,14,15,17,20,32. The percentage of high/positive COX-2 expression was >50% in 15 studies,6,8,10,11,13–19,21,22,31,34,36 and the remaining 10 studies shared the percentage of high/positive COX-2 expression <50% 7,9,12,20,21,23,24,32,33.…”

Cyclin A overexpression is associated with chemosensitivity to paclitaxel-based chemotherapy in patients with esophageal squamous cell carcinoma

“…The positive cyclin A expression rate was 64.6% (31/48) in 48 cases with ESCC, and 20% (2/10) in 10 cases with normal esophageal mucosa. Comparisons between cyclin A expression pattern in ESCC and normal tissues have been revealed in our previous studies (10,11).…”

“…As a critical regulatory protein, cyclin A may promote G2/M phase transition and mitosis (8). Our previous studies have revealed that overexpression of cyclin A in ESCC is associated with cell proliferation and survival (9)(10)(11). As the clinical application of immunohistochemistry is relatively cost-effective (2), in this study, we explore the possibility of evaluating paclitaxel efficacy by examining the correlation between cyclin A expression and efficacy of paclitaxel-based chemotherapy in patients with ESCC. )…”