Absence of High-Risk Human Papillomavirus (HPV) Detection in Endocervical Adenocarcinoma with Gastric Morphology and Phenotype
Absence of High-Risk Human Papillomavirus (HPV) Detection in Endocervical Adenocarcinoma with Gastric Morphology and Phenotype
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DOI：
10.2353/ajpath.2010.100323
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发表时间：
2010-11-01
影响因子：
6
通讯作者：
Nishimura, Ryuichiro
中科院分区：
文献类型：
--
作者：
Kusanagi, Yasuki;Kojima, Atsumi;Nishimura, Ryuichiro
子宫颈内型粘液腺癌（AC）的一个子集表现出胃的表型和形态，如在微小偏离AC的情况下，其中人乳头状瘤病毒（HPV）的存在已很少检测到报告。为了研究胃型AC病例中HPV非依赖性致癌途径，我们使用基于PCR的分型方法和p16（INK 4a）（一种细胞周期蛋白依赖性激酶抑制剂，在癌性和癌前宫颈组织中过表达，使其成为宫颈癌病例的理想生物标志物）的免疫组化，研究了52例非鳞状细胞癌中常见的高危型HPV（hr-HPV）状态。使用新的形态学标准，52例癌中有7例（13.5%）被指定为胃型AC，所有这些癌均为hr-HPV DNA和p16（INK 4a）阴性。在腺鳞癌和神经内分泌癌中，hr-HPV DNA阳性率分别为90%（28/31）和94%（29/31），hr-HPV DNA阳性率分别为86%（6/7）和82%（5/6）。p16（INK 4a）在两种癌中的阳性率分别为86%（6/7）和100%（6/6）。我们的数据表明，胃型AC似乎代表一种致癌hr-HPV非依赖性肿瘤，因此是HPV DNA检测和疫苗接种的潜在陷阱。(Am J Pathol 2010，177：2169-2175; DOI：10.2353/ajpath.2010.100323）
A subset of endocervical-type mucinous adenocarcinomas (ACs) of the uterine cervix exhibit a gastric phenotype and morphology, as reported in cases of minimal deviation AC in which the presence of human papillomavirus (HPV) has been rarely detected. To investigate the HPV-independent pathway of carcinogenesis in cases of gastric-type AC, we investigated the common high-risk HPV (hr-HPV) status in 52 nonsquamous cell carcinomas, using a PCR-based typing method and immunohistochemistry of p16(INK4a) (a cyclin-dependent kinase inhibitor that is overexpressed in both cancerous and precancerous cervical tissue, making it an ideal biomarker for cervical cancer cases). Using novel morphological criteria, seven of 52 (13.5%) carcinomas were designated as gastric-type ACs, all of which were negative for both hr-HPV DNA and p16(INK4a). Nongastric-type ACs were frequently positive for both hr-HPV DNA (90%, 28/31) and p16(INK4a) (94%, 29/31) with adenosquamous and neuroendocrine carcinomas demonstrating the presence of hr-HPV DNA in 86% (6/7) and 82% (5/6) of cases, respectively. In these two types of carcinoma, 86% (6/7) and 100% (6/6) were positive for p16(INK4a), respectively. Our data suggests that gastric-type AC appears to represent an oncogenic hr-HPV-independent neoplasm and therefore is a potential pitfall of HPV DNA testing and vaccination. (Am J Pathol 2010, 177:2169-2175; DOI: 10.2353/ajpath.2010.100323)