Kayo Kayahashi1, Yasunari Mizumoto2, Ayumi Matsuoka1, Takeshi Obata1, Junpei Iwadare1, Mitsuhiro Nakamura1, Takiko Daikoku3, Hiroshi Fujiwara1. 1. Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan. 2. Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan. yas1025@med.kanazawa-u.ac.jp. 3. Institute for Experimantal Animals, Advanced Science Research Center, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
Abstract
BACKGROUND: Aberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment. Ovarian cancer, the leading cause of death among gynecologic malignancies, is classified into four histological subtypes: serous, mucinous, endometrioid, and clear cell, and each has distinct biological behavior. Although a negative survival impact in serous ovarian cancer patients and some functional role in peritoneal dissemination have been reported, differences of P-cadherin expression in histological subtypes and the proportion and distribution of positive cells remain to be investigated. The aims of this study were to clarify the histological and distributional profiles of P-cadherin expression in ovarian cancer for development of target-therapy in near future. METHODS: A total of 162 primary, 60 metastatic, and 8 recurrent tumors (all cases from 162 ovarian cancer patients) were enrolled in the study. Immunohistochemistry was performed for P-cadherin expression. Associations with clinicopathological characteristics and survival were analyzed. RESULTS: P-cadherin expression showed a strong correlation with the FIGO stage, histological subtypes, positive peritoneal dissemination (P < 0.01), positive distant metastasis (P < 0.05), and trend toward negative overall survival probability (P = 0.050). P-cadherin was intensely and broadly expressed in mucinous, endometrioid, and serous subtypes (P < 0.01). Disseminated tumors demonstrated similar P-cadherin expression to primary tumors whereas metastatic lymph nodes demonstrated significantly decreased expression (P < 0.01). CONCLUSIONS: Mucinous, endometrioid, and serous ovarian cancer patients accompanied with peritoneal disseminations are the most potent candidates for P-cadherin targeted drug delivery strategies. P-cadherin-targeted therapy may benefit and improve survival of poor-prognosis populations.
BACKGROUND: Aberrant expression of P-cadherin has been reported in various cancers, and has been attracting attention as a target for cancer treatment. Ovarian cancer, the leading cause of death among gynecologic malignancies, is classified into four histological subtypes: serous, mucinous, endometrioid, and clear cell, and each has distinct biological behavior. Although a negative survival impact in serous ovarian cancerpatients and some functional role in peritoneal dissemination have been reported, differences of P-cadherin expression in histological subtypes and the proportion and distribution of positive cells remain to be investigated. The aims of this study were to clarify the histological and distributional profiles of P-cadherin expression in ovarian cancer for development of target-therapy in near future. METHODS: A total of 162 primary, 60 metastatic, and 8 recurrent tumors (all cases from 162 ovarian cancerpatients) were enrolled in the study. Immunohistochemistry was performed for P-cadherin expression. Associations with clinicopathological characteristics and survival were analyzed. RESULTS:P-cadherin expression showed a strong correlation with the FIGO stage, histological subtypes, positive peritoneal dissemination (P < 0.01), positive distant metastasis (P < 0.05), and trend toward negative overall survival probability (P = 0.050). P-cadherin was intensely and broadly expressed in mucinous, endometrioid, and serous subtypes (P < 0.01). Disseminated tumors demonstrated similar P-cadherin expression to primary tumors whereas metastatic lymph nodes demonstrated significantly decreased expression (P < 0.01). CONCLUSIONS: Mucinous, endometrioid, and serous ovarian cancerpatients accompanied with peritoneal disseminations are the most potent candidates for P-cadherin targeted drug delivery strategies. P-cadherin-targeted therapy may benefit and improve survival of poor-prognosis populations.
Authors: E L Sievers; R A Larson; E A Stadtmauer; E Estey; B Löwenberg; H Dombret; C Karanes; M Theobald; J M Bennett; M L Sherman; M S Berger; C B Eten; M R Loken; J J van Dongen; I D Bernstein; F R Appelbaum Journal: J Clin Oncol Date: 2001-07-01 Impact factor: 44.544