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AGO卵巢癌研究组分析:一系列p16INK4a阳性黏液性或子宫内膜样晚期卵巢癌中无转移性宫颈腺癌

No metastatic cervical adenocarcinomas in a series of p16INK4a-positive mucinous or endometrioid advanced ovarian carcinomas: an analysis of the AGO Ovarian Cancer Study Group.

作者信息

Wentzensen Nicolas, du Bois Andreas, Kommoss Stefan, Pfisterer Jacobus, von Knebel Doeberitz Magnus, Schmidt Dietmar, Kommoss Friedrich

机构信息

Department of Applied Tumor Biology,Institute of Pathology, University of Heidelberg, Mannheim, Germany.

出版信息

Int J Gynecol Pathol. 2008 Jan;27(1):18-23. doi: 10.1097/pgp.0b013e318074b83f.

DOI:10.1097/pgp.0b013e318074b83f
PMID:18156969
Abstract

Epithelial ovarian cancers may represent secondary manifestations of occult extraovarian carcinomas. Such tumors may be misdiagnosed as primary ovarian carcinomas clinically and pathologically. In a recent study, several cases of cervical cancer metastases with primary manifestation as mucinous or endometrioid ovarian carcinomas were described. In all cases, human papillomavirus (HPV) DNA and diffuse p16 immunostaining were detected in the ovarian tumor tissues. To estimate the frequency of occult metastatic endocervical adenocarcinomas in a series of mucinous or endometrioid ovarian carcinomas, 24 ovarian cancers with mucinous and 50 with endometrioid differentiation from the Arbeitsgemeinschaft Gynaekologische Onkologie OVAR-3 database were analyzed for HPV and p16 positivity. The p16 immunostaining was performed using the p16 histology kit (Dako, Glostrup, Denmark), and both nuclear and cytoplasmic staining results were considered positive. Human papillomavirus polymerase chain reaction analysis was performed using 2 consensus primer systems (GP5/GP6 and PGMY09/11) and HPV-16- and HPV-18-specific primers from the L1 and the E6 regions. Six (8%) of 74 tumors were p16-negative, 13 (18%) of 74 showed single positive cells, 28 (38%) of 74 showed focal homogeneous staining, and 27 (36%) of 74 showed complete diffuse staining. In several independent amplifications of different regions of the HPV genome, none of the 73 tumors available for analysis showed the presence of HPV DNA. No ovarian metastases of endocervical adenocarcinomas were found among mucinous and endometrioid adenocarcinomas from a large chemotherapy trial of advanced stage ovarian carcinomas. The p16 staining detected in many primary ovarian adenocarcinomas in the present series seems independent from HPV oncogene activity.

摘要

上皮性卵巢癌可能是隐匿性卵巢外癌的继发性表现。这类肿瘤在临床和病理上可能被误诊为原发性卵巢癌。在最近一项研究中,描述了几例以黏液性或子宫内膜样卵巢癌为主要表现的宫颈癌转移病例。在所有病例中,卵巢肿瘤组织中均检测到人类乳头瘤病毒(HPV)DNA和弥漫性p16免疫染色。为了估计一系列黏液性或子宫内膜样卵巢癌中隐匿性转移性宫颈内膜腺癌的发生率,对来自妇科肿瘤协作组OVAR - 3数据库的24例黏液性卵巢癌和50例子宫内膜样分化卵巢癌进行了HPV和p16阳性分析。使用p16组织学试剂盒(丹麦哥本哈根格罗斯特鲁普的达科公司)进行p16免疫染色,细胞核和细胞质染色结果均视为阳性。使用2种共有引物系统(GP5/GP6和PGMY09/11)以及来自L1和E6区域的HPV - 16和HPV - 18特异性引物进行人类乳头瘤病毒聚合酶链反应分析。74例肿瘤中有6例(8%)p16阴性,74例中有13例(18%)显示单个阳性细胞,74例中有28例(38%)显示局灶性均匀染色,74例中有27例(36%)显示完全弥漫性染色。在HPV基因组不同区域的几次独立扩增中,可供分析的73例肿瘤均未显示HPV DNA的存在。在一项晚期卵巢癌大型化疗试验的黏液性和子宫内膜样腺癌中,未发现宫颈内膜腺癌的卵巢转移。本系列中许多原发性卵巢腺癌检测到的p16染色似乎与HPV癌基因活性无关。

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