Increased cyclooxygenase-2 (COX-2) and P-glycoprotein-170 (MDR1) expression is associated with chemotherapy resistance and poor prognosis. Analysis in ovarian carcinoma patients with low and high survival

Abstract

The aim of the study is to test the prognostic value of cyclooxygenase-2 (COX-2) and P-glycoprotein in relation to responsiveness to chemotherapy in ovarian carcinoma patients with "shorter and longer" survival. We evaluated 52 ovarian carcinomas homogeneous for stage, histologic type, grade of differentiation, and surgical and chemotherapeutic treatment. Twenty-eight of the patients had died of progression of disease no later than 2 years after primary surgical treatment, while 24 patients were alive with no evident disease 5 years after primary surgical treatment. In logistic regression analysis, COX-2 and P-glycoprotein, when analyzed one by one, are significant (P= 0.017 and P < 0.0005, respectively). P-glycoprotein is correlated with COX-2 (P= 0.008, Fisher's exact test); moreover, both COX-2 and the P-glycoprotein are correlated with clinical response to chemotherapy (P= 0.022 and P < 0.0005, respectively, Chi-square test). Our data suggest that COX-2 and P-glycoprotein may have prognostic significance in advanced ovarian serous carcinoma. The COX-2 and the P-glycoprotein overexpressions are correlated to one another and both with a progression of disease during the first-line chemotherapy. The administration of a COX-2 inhibitor in association with chemotherapy in ovarian carcinoma patients may improve the tumor chemosensibility and the overall survival.

Effect of apoptotic and proliferative indices, P-glycoprotein and survivin expression on prognosis in laryngeal squamous cell carcinoma

“…As stated above, it is demonstrated that P-gp may have an effect on drug resistance and disease progression by its biologic activity of anti-apoptosis in LSCC. As widely reported in literature, the relationship between P-gp expression and patients' survival in different tumor is variable [15,16,28]. In this series, we was the first to investigate the prognostic value of P-gp expression in laryngeal carcinoma and found that up-expression of P-gp was associated with a shorter overall survival in laryngeal carcinoma.…”

“…The inconsistencies among these studies may be attributed to the intrinsic distinctions in the regulation mechanisms for cell proliferation in various tumors. Moreover, remarkable attention has already been directed to the role of P-gp in the neoplastic progression [15,16,28] but unfortunately its role in LSCC is currently unclear. Our previous in vitro work has proved that P-gp plays a major role in the invasiveness of the laryngeal cancer Hep-2 cell line [14].…”

“…In addition, P-gp is also involved in the regulation of caspase-dependent apoptosis [12], proliferation [13], and invasion of malignant cells [14]. Moreover, it is reported that P-gp overexpression is associated with a worse prognosis in several neoplasms [15,16]. Unfortunately, we have not found any reports about the prognostic significance of P-gp expression for patients with LSCC so far.…”

Predicting the Response of Advanced Cervical and Ovarian Tumors to Therapy

“…Similarly, increased cyclooxygenase-2 expression in ovarian cancer has been correlated with chemotherapy resistance and may ultimately be useful in planning individualized therapy (58)(59)(60). Glutathione concentration in ovarian tumors may be used to predict response to second line chemotherapy such as cisplatin and etoposide (61), while the expression of insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 has been shown to indicate endocrine responsiveness in patients treated with the aromatase inhibitor letrozole (62).…”

Chemotherapy and Mechanisms of Resistance in Breast Cancer

“…In endometrial carcinoma, the immunohistochemical overexpression of Pgp is seen especially in premenopausal patients compared to patients of advanced age (Terek et al, 2003). In ovarian cancer, overexpression of MDR-1 gene is associated with decreased disease-free survival and tumor progression during chemotherapy (Kavallaris et al, 1996;Raspollini et al, 2005). In breast carcinoma, the expression of Pgp shows great heterogeneity due to the detection methods and different degrees of their induction by the use of multiple chemotherapeutic agents (Trock et al, 1997;Leonessa, Clarke, 2003).…”