Jochmus I, Dürst M, Reid R, Altmann A, Bijward K E, Gissmann L, Jenson A B
Department of Pathology, Georgetown University School of Medicine, Washington, DC.
Hum Pathol. 1993 May;24(5):519-24. doi: 10.1016/0046-8177(93)90164-c.
To determine whether expression of the human papillomavirus (HPV) type 16 E7 open reading frame influences expression of major histocompatibility complex (MHC) antigens on the surface of squamous epithelial cells, serial frozen sections from seven HPV type 16-positive, high-grade vulvar intraepithelial neoplasia (VIN 2-3) lesions were tested for viral transcription by RNA-RNA in situ hybridization, for MHC expression by immunohistochemical staining with antibodies to MHC class I and II molecules, and for keratinocyte differentiation by immunohistochemical staining with anti-filaggrin and cytokeratin 10 antibodies. Despite the histologic appearance of high-grade VIN lesions, expression patterns of cytokeratin 10 and filaggrin suggested a certain degree of keratinocyte differentiation in all specimens. These differentiation markers were especially prominent in parakeratotic and hyperkeratotic superficial areas, which did not express MHC antigens or contain E7 mRNA. Expression of MHC class I molecules within dysplastic tissues was greater than within HPV type 16-negative, normal vulvar epithelium from the same patients. In five of the VIN 2-3 specimens anti-MHC class I antibodies reacted more strongly with cells of the basal and suprabasal layers than with cells of the epithelial surface. In one lesion basal cells stained less intensively than surface cells, whereas in another specimen all epithelial layers were equally MHC class I positive. Staining with anti-MHC class II antibodies was generally restricted to isolated foci, representing invading lymphocytes, tissue macrophages, and Langerhans cells. In two lesions, however, there was heterogeneous keratinocyte expression of MHC class II proteins, perhaps due to inflammation. Major histocompatibility complex antigen detection was independent of the presence or distribution pattern of E7-specific transcripts. Hence, a correlation between MHC and E7 expression appears unlikely in warty VIN lesions.
为了确定人乳头瘤病毒16型（HPV-16）E7开放阅读框的表达是否会影响鳞状上皮细胞表面主要组织相容性复合体（MHC）抗原的表达，我们对7例HPV-16阳性的高级别外阴上皮内瘤变（VIN 2-3）病变的连续冰冻切片进行了检测，采用RNA-RNA原位杂交检测病毒转录情况，用抗MHC I类和II类分子抗体进行免疫组织化学染色检测MHC表达情况，并用抗丝聚蛋白和细胞角蛋白10抗体进行免疫组织化学染色检测角质形成细胞分化情况。尽管高级别VIN病变具有组织学表现，但所有标本中细胞角蛋白10和丝聚蛋白的表达模式均提示一定程度的角质形成细胞分化。这些分化标志物在不全角化和过度角化的浅表区域尤为突出，这些区域不表达MHC抗原或不含E7 mRNA。发育异常组织中MHC I类分子的表达高于同一患者的HPV-16阴性正常外阴上皮。在5例VIN 2-3标本中，抗MHC I类抗体与基底层和基底上层细胞的反应比与上皮表面细胞的反应更强。在一个病变中，基底细胞的染色强度低于表面细胞，而在另一个标本中，所有上皮层的MHC I类均呈同等阳性。抗MHC II类抗体染色通常局限于孤立的病灶，代表浸润的淋巴细胞、组织巨噬细胞和朗格汉斯细胞。然而，在两个病变中，MHC II类蛋白存在角质形成细胞异质性表达，可能是由于炎症所致。MHC抗原检测与E7特异性转录本的存在或分布模式无关。因此，在疣状VIN病变中，MHC与E7表达之间似乎不存在相关性。
