有腹膜转移的黏液性、子宫内膜样和浆液性卵巢癌是 P-钙黏蛋白靶向治疗的有力候选者：一项回顾性队列研究。

Mucinous, endometrioid, and serous ovarian cancers with peritoneal dissemination are potent candidates for P-cadherin targeted therapy: a retrospective cohort study.

机构信息

Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

Institute for Experimantal Animals, Advanced Science Research Center, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

出版信息

BMC Cancer. 2021 Jan 7;21(1):32. doi: 10.1186/s12885-020-07737-w.

DOI:10.1186/s12885-020-07737-w

PMID:33413178

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7791827/

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.

摘要

背景

P-钙黏蛋白在各种癌症中的异常表达已被报道，并作为癌症治疗的靶点受到关注。卵巢癌是妇科恶性肿瘤中导致死亡的主要原因，分为四种组织学亚型：浆液性、黏液性、子宫内膜样和透明细胞，每种亚型都具有不同的生物学行为。虽然已经报道了 P-钙黏蛋白在浆液性卵巢癌患者中的阴性生存影响和在腹膜扩散中的一些功能作用，但在组织学亚型中的表达差异以及阳性细胞的比例和分布仍有待研究。本研究旨在阐明卵巢癌中 P-钙黏蛋白表达的组织学和分布特征，以便在不久的将来开发靶向治疗方法。

方法

本研究共纳入 162 例原发性、60 例转移性和 8 例复发性肿瘤（所有病例均来自 162 例卵巢癌患者）。进行 P-钙黏蛋白表达的免疫组织化学检测。分析与临床病理特征和生存的关系。

结果

P-钙黏蛋白表达与 FIGO 分期、组织学亚型、阳性腹膜扩散（P<0.01）、阳性远处转移（P<0.05）和总生存概率呈负相关（P=0.050）。P-钙黏蛋白在黏液性、子宫内膜样和浆液性亚型中表达强烈且广泛（P<0.01）。播散性肿瘤的 P-钙黏蛋白表达与原发性肿瘤相似，而转移性淋巴结的表达显著降低（P<0.01）。