Santos Mónica, Landolfi Stefania, Olivella Anna, Lloveras Belen, Klaustermeier Joellen, Suárez Helena, Alòs Llúcia, Puig-Tintoré Lluís M, Campo Elias, Ordi Jaume
Department of Pathology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Am J Surg Pathol. 2006 Nov;30(11):1347-56. doi: 10.1097/01.pas.0000213251.82940.bf.
Two types of vulvar squamous cell carcinomas (VSCCs) are recognized according to their relationship to human papillomavirus (HPV). Basaloid or warty carcinomas are considered HPV-associated tumors, whereas differentiated keratinizing neoplasms are considered non-HPV-associated. Recently, immunohistochemical detection of p16 and p53 has been proposed to differentiate these 2 types of VSCCs. We conducted a histologic study with immunohistochemical evaluation of p16 and p53 and HPV detection and typing by polymerase chain reaction using 2 different sets of primers in 92 cases of VSCCs to evaluate the usefulness of immunohistochemistry in the classification of VSCCs and to describe the clinico-pathologic characteristics of both types of VSCCs. HPV was detected in 16/92 (17.4%) specimens, HPV16 being identified in 75% of positive cases. A significant number of discrepancies between histology and HPV detection were observed, with 37.5% of HPV-positive tumors being keratinizing and 9.2% of HPV-negative carcinomas showing basaloid or warty features. Diffuse positivity for p16 and p53 was observed in 100% and 6.2% of HPV-positive tumors and in 2.3% and 64.5% of HPV-negative neoplasms, respectively. The sensitivity and specificity of p16 immunostaining to detect HPV-associated carcinomas (100% and 98.7%, respectively) were better than those of histologic criteria (93.8% and 35.5%) and of p53 negative stain (62.5% and 93.4%). Vulvar intraepithelial neoplasia grade 3 of basaloid/warty type was identified in 53.8% HPV-positive tumors, including 3 keratinizing tumors. All these cases were p16 positive and p53 negative. Vulvar intraepithelial neoplasia grade 3 of differentiated type was observed in 45.6% of HPV-negative cases; 90.8% of them were positive for p53 but all were negative for p16. No differences in age, stage, or development of recurrence were observed between HPV-positive and negative tumors. In summary, the current morphologic criteria to discriminate HPV-positive and negative VSCCs have a significant overlap. Immunostaining for p16 is a reliable marker for HPV-positive VSSCs, which improves the results of histologic classification.
根据与人类乳头瘤病毒（HPV）的关系，可识别出两种类型的外阴鳞状细胞癌（VSCC）。基底样癌或疣状癌被认为是HPV相关肿瘤，而分化型角化性肿瘤被认为是非HPV相关肿瘤。最近，有人提出通过免疫组化检测p16和p53来区分这两种类型的VSCC。我们对92例VSCC进行了组织学研究，通过免疫组化评估p16和p53，并使用两组不同引物通过聚合酶链反应进行HPV检测和分型，以评估免疫组化在VSCC分类中的实用性，并描述两种类型VSCC的临床病理特征。92份标本中有16份（17.4%）检测到HPV，75%的阳性病例中鉴定出HPV16。观察到组织学与HPV检测之间存在大量差异，37.5%的HPV阳性肿瘤为角化性，9.2%的HPV阴性癌表现为基底样或疣状特征。分别在100%和6.2%的HPV阳性肿瘤以及2.3%和64.5%的HPV阴性肿瘤中观察到p16和p53弥漫性阳性。p16免疫染色检测HPV相关癌的敏感性和特异性（分别为100%和98.7%）优于组织学标准（93.8%和35.5%）以及p53阴性染色（62.5%和93.4%）。在53.8%的HPV阳性肿瘤中鉴定出基底样/疣状型外阴上皮内瘤变3级，包括3例角化性肿瘤。所有这些病例p16阳性且p53阴性。在45.6%的HPV阴性病例中观察到分化型外阴上皮内瘤变3级；其中90.8%的病例p53阳性，但所有病例p16均为阴性。HPV阳性和阴性肿瘤在年龄、分期或复发发展方面未观察到差异。总之，目前区分HPV阳性和阴性VSCC的形态学标准存在显著重叠。p16免疫染色是HPV阳性VSSC的可靠标志物，可改善组织学分类结果。
