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Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas.
Gynecol Oncol. 2006 Jan; 100(1):152-9.GO

Abstract

OBJECTIVE

Multidrug resistance (MDR) to chemotherapy is a major obstacle in attempts to improve the clinical outcome of ovarian carcinoma patients. The MDR-related phenotype is associated with over-expression of certain drug transporters, such as P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and lung resistance protein (LRP). The aim of this study was to evaluate the extent and prognostic significance of MDR-related protein expression in ovarian serous carcinomas. In addition, we correlated expression of these proteins with the apoptosis-related proteins p53, bcl-2, and bax.

METHODS

Consecutive sections from 60 cases of ovarian serous carcinoma were assessed immunohistochemically for expression of P-gp, MRP1, LRP, p53, bcl-2, and bax. The level of protein expression was scored based on staining intensity and extent.

RESULTS

Strong P-gp expression was observed in 12 (20%), MRP1 in 39 (65%), LRP in 27 (45%), p53 in 45 (75%), bcl-2 in 25 (41.7%), and bax in 30 (50%) of the 60 tumors. MRP1 expression was associated with both p53 and bcl-2 expressions (P = 0.01 and P = 0.03, respectively). Univariate analysis of survival revealed a significant inverse correlation between P-gp expression and patient survival (P = 0.015). Moreover, P-gp expression was significantly increased in tumors of patients unresponsive to chemotherapy (P = 0.009). Multivariate analysis revealed that only FIGO stage and P-gp expression were useful negative independent predictors of survival (P = 0.035 and P = 0.045, respectively).

CONCLUSIONS

Our pilot study demonstrates that P-gp expression may be a reliable independent prognostic factor of survival in patients with ovarian serous carcinoma. Moreover, P-gp immunostaining may be useful for dividing ovarian carcinoma patients into chemoresponsive and chemoresistant groups.

Authors+Show Affiliations

Department of Pathology, Carmel Medical Center and Rappaport Faculty of Medicine, Technion University, Haifa, Israel. eyakirevich@lifespan.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16198399

Citation

Yakirevich, Evgeny, et al. "Multidrug Resistance-related Phenotype and Apoptosis-related Protein Expression in Ovarian Serous Carcinomas." Gynecologic Oncology, vol. 100, no. 1, 2006, pp. 152-9.
Yakirevich E, Sabo E, Naroditsky I, et al. Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas. Gynecol Oncol. 2006;100(1):152-9.
Yakirevich, E., Sabo, E., Naroditsky, I., Sova, Y., Lavie, O., & Resnick, M. B. (2006). Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas. Gynecologic Oncology, 100(1), 152-9.
Yakirevich E, et al. Multidrug Resistance-related Phenotype and Apoptosis-related Protein Expression in Ovarian Serous Carcinomas. Gynecol Oncol. 2006;100(1):152-9. PubMed PMID: 16198399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas. AU - Yakirevich,Evgeny, AU - Sabo,Edmond, AU - Naroditsky,Inna, AU - Sova,Yanina, AU - Lavie,Ofer, AU - Resnick,Murray B, Y1 - 2005/09/29/ PY - 2005/03/25/received PY - 2005/07/27/revised PY - 2005/08/16/accepted PY - 2005/10/4/pubmed PY - 2006/2/10/medline PY - 2005/10/4/entrez SP - 152 EP - 9 JF - Gynecologic oncology JO - Gynecol. Oncol. VL - 100 IS - 1 N2 - OBJECTIVE: Multidrug resistance (MDR) to chemotherapy is a major obstacle in attempts to improve the clinical outcome of ovarian carcinoma patients. The MDR-related phenotype is associated with over-expression of certain drug transporters, such as P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and lung resistance protein (LRP). The aim of this study was to evaluate the extent and prognostic significance of MDR-related protein expression in ovarian serous carcinomas. In addition, we correlated expression of these proteins with the apoptosis-related proteins p53, bcl-2, and bax. METHODS: Consecutive sections from 60 cases of ovarian serous carcinoma were assessed immunohistochemically for expression of P-gp, MRP1, LRP, p53, bcl-2, and bax. The level of protein expression was scored based on staining intensity and extent. RESULTS: Strong P-gp expression was observed in 12 (20%), MRP1 in 39 (65%), LRP in 27 (45%), p53 in 45 (75%), bcl-2 in 25 (41.7%), and bax in 30 (50%) of the 60 tumors. MRP1 expression was associated with both p53 and bcl-2 expressions (P = 0.01 and P = 0.03, respectively). Univariate analysis of survival revealed a significant inverse correlation between P-gp expression and patient survival (P = 0.015). Moreover, P-gp expression was significantly increased in tumors of patients unresponsive to chemotherapy (P = 0.009). Multivariate analysis revealed that only FIGO stage and P-gp expression were useful negative independent predictors of survival (P = 0.035 and P = 0.045, respectively). CONCLUSIONS: Our pilot study demonstrates that P-gp expression may be a reliable independent prognostic factor of survival in patients with ovarian serous carcinoma. Moreover, P-gp immunostaining may be useful for dividing ovarian carcinoma patients into chemoresponsive and chemoresistant groups. SN - 0090-8258 UR - https://www.unboundmedicine.com/medline/citation/16198399/Multidrug_resistance_related_phenotype_and_apoptosis_related_protein_expression_in_ovarian_serous_carcinomas_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-8258(05)00708-0 DB - PRIME DP - Unbound Medicine ER -