Overexpression of cyclooxygenase‐2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy

Abstract

BACKGROUND The objective of this study was to determine whether cyclooxygenase‐2 (COX‐2) overexpression was an indicator of prognosis in patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine cervical carcinoma who underwent radiation and concurrent chemotherapy. METHODS Seventy‐five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the uterine cervix who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996 were divided into two groups according to their COX‐2 level in an immunohistochemical study: the COX‐2 negative group (n = 54 patients) and the COX‐2 positive group (n = 21 patients). The clinicopathologic features, patterns of treatment failure, and survival data for patients in the COX‐2 positive group were compared with data from the patients in the COX‐2 negative group. Univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival. RESULTS In the immunohistochemical study, COX‐2 overexpression was observed in approximately 30% of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed regression to the initial treatment, the treatment failure rate of patients in the COX‐2 positive group was much higher compared with the treatment failure rate of patients in the COX‐2 negative group. The higher incidence of central failure and lymph node failure for patients in the COX‐2 positive group was statistically significant (48% for the COX‐2 positive group vs. 13% for the COX‐2 negative group). However, there was no difference in the incidence of hematogenous metastases between the two groups (5% for the COX‐2 positive group vs. 7% for the COX‐2 negative group). In addition, increased COX‐2 expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 9 months in the COX‐2 positive group vs. 26 months in the COX‐2 negative group). Compared with patients in the COX‐2 negative group, patients in the COX‐2 positive group had lower overall actuarial and disease free survival rates (overall 5‐year actuarial survival rates: 56% for the COX‐2 positive group vs. 94% for the COX‐2 negative group; P = 0.003). Univariate and multivariate analyses showed that COX‐2 overexpression was an independent prognostic factor that surpassed other well‐known clinicopathologic parameters. CONCLUSIONS COX‐2 overexpression can be used as a potent molecular risk factor in patients with FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy. Cancer 2002;95:531–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10684

The role of COX-2 in rectal cancer treated with preoperative radiotherapy

“…These data are in line with one published study on human rectal cancer pretreated with chemoradiotherapy [45] but are not in accordance with the results reported in studies on squamous cell carcinoma of head and neck and cervix treated with radiotherapy alone or radiochemotherapy [39,27,9,18].…”

“…In oral squamous cell carcinoma [39] and in laryngeal cancer [27] elevated COX-2 expression has been associated with radio resistance and diminished survival. Expression of COX-2 was also correlated with poor prognosis in squamous cell carcinoma of the uterine cervix treated with radiation therapy [9,18].…”

Expression of cyclooxygenase-2 related to angiogenesis in uterine cervical cancers

“…In immunohistochemistry, COX-2 overexpression can be used as a potent molecular risk factor in patients with stage IIB squamous cell carcinoma of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy [39]. In surgically treated stage IB cervical cancer patients, COX-2 is expressed when lymph node or parametrial involvement is present, and COX-2 may downregulate apoptotic processes and thus enhance tumor invasion and metastasis [40].…”

Tumor Markers of Neo-Adjuvant Chemo-Radiation Response in Rectal Cancer

“…COX2 inhibition in conjunction with radiation can significantly enhance tumor response by blocking prostaglandin release (Kishi, Petersen et al 2000). In laryngeal (Nix, Lind et al 2004) and cervical cancers (Kim, Kim et al 2004), (Kim, Kim et al 2002), COX 2 expression in pre treatment biopsies may be indicative of treatment response to CRT. Cox2 has been evaluated in pre rectal biopsies (Watwe, Javle et al 2005), (Kobayashi, Hashiguchi et al 2007), (de Heer, Gosens et al 2007), (Giralt, Navalpotro et al 2006), (Min, Choi et al 2008), (Smith, Reynolds et al 2006).…”