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Microanatomy of the cervical and anorectal squamocolumnar junctions: a proposed model for anatomical differences in HPV-related cancer risk.

子宫颈和肛门直肠鳞柱交界区显微解剖:HPV相关癌症风险的解剖学差异模型

Yang EJ,Quick MC,Hanamornroongruang S,Lai K,Doyle LA,McKeon FD,Xian W,Crum CP,Herfs M
阅读:800 Modern PathologyJul 2015; 28 (7): 882 - 1010:994-1000 

Abstract

Human papilloma virus (HPV) infection causes cancers and their precursors (high-grade squamous intraepithelial lesions) near cervical and anal squamocolumnar junctions. Recently described cervical squamocolumnar junction cells are putative residual embryonic cells near the cervical transformation zone. These cells appear multipotential and share an identical immunophenotype (strongly CK7-positive) with over 90% of high-grade squamous intraepithelial lesions and cervical carcinomas. However, because the number of new cervical cancers discovered yearly world wide is 17-fold that of anal cancer, we posed the hypothesis that this difference in cancer risk reflects differences in the transition zones at the two sites. The microanatomy of the normal anal transformation zone (n=37) and topography and immunophenotype of anal squamous neoplasms (n=97) were studied. A discrete anal transition zone was composed of multilayered CK7-positive/p63-negative superficial columnar cells and an uninterrupted layer of CK7-negative/p63-positive basal cells. The CK7-negative/p63-positive basal cells were continuous with-and identical in appearance to-the basal cells of the mature squamous epithelium. This was in contrast to the cervical squamocolumnar junction, which harbored a single-layered CK7-positive/p63-negative squamocolumnar junction cell population. Of the 97 anal intraepithelial neoplasia/squamous cell carcinomas evaluated, only 27% (26/97) appeared to originate near the anal transition zone and only 23% (22/97) were CK7-positive. This study thus reveals two fundamental differences between the anus and the cervix: (1) the anal transition zone does not harbor a single monolayer of residual undifferentiated embryonic cells and (2) the dominant tumor immunophenotype is in keeping with an origin in metaplastic (CK7-negative) squamous rather than squamocolumnar junction (CK7-positive) epithelium. The implication is that, at birth, the embryonic cells in the anal transition zone have already begun to differentiate, presenting a metaplasia that-similar to vaginal and vulvar epithelium-is less prone to HPV-directed carcinogenesis. This in turn underscores the link between cancer risk and a very small and discrete population of vulnerable squamocolumnar junction cells in the cervix.

摘要

宫颈和肛门鳞柱交界区人乳头状瘤病毒(HPV)感染可引起癌症及其癌前病变(高级别鳞状上皮内瘤变)。最近描述宫颈鳞柱交界处细胞是宫颈移行区潜在的胚胎残余细胞。这些细胞显示出多项潜能,并与90%以上的高级别鳞状上皮内瘤变和宫颈癌有相同免疫表型(CK7强阳性)。然而,鉴于每年世界范围内新发宫颈癌数量是新发肛门癌的17倍,我们提出一种假设,即这种癌症风险的差异反映了两个部位移行区的差异。

我们研究了肛门鳞状细胞肿瘤(n = 97)、肛门正常转化区(n = 37)的显微解剖三维形态和免疫表型。肛门的不连续移行区由多层CK7阳性/ p63阴性表层柱状细胞和CK7阴性/ p63阳性的连续性基底细胞组成。CK7阴性/ p63阳性基底细胞与成熟鳞状上皮基底细胞相连续并形态一致。这与宫颈鳞柱交界处相反,后者包含单层CK7阳性/ p63阴性鳞柱交界区细胞群。本研究中97例肛门上皮内肿瘤/鳞状细胞癌,只有27%(26/97)显示起源于肛门移行区附近,只有23%(22/97)CK7阳性。

因此,本研究揭示了肛门和子宫颈的两个根本性差异:

(1)肛门移行区没有单层残余未分化胚胎细胞;

(2)肿瘤细胞占主导地位的免疫表型与化生性鳞状上皮(CK7阴性)而非鳞柱交界处细胞(CK7阳性)一致。

这意味着,在出生时,肛门移行区胚胎细胞已经开始分化,并呈现出化生-类似于阴道及外阴上皮-不易被HPV感染致癌。这也强调了癌症风险与非常少的且不连续的脆弱宫颈鳞柱交界区细胞群之间的关系。

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