Cheng Angela S, Karnezis Anthony N, Jordan Suzanne, Singh Naveena, McAlpine Jessica N, Gilks C Blake
Department of Cellular Pathology (S.J., N.S.), Barts Health NHS Trust, London, United Kingdom Department of Pathology and Laboratory Medicine (A.S.C., A.N.K., C.B.G.), Vancouver General Hospital Department of Obstetrics and Gynecology (J.N.M.), Division of Gynecologic Oncology, University of British Columbia, Vancouver, BC, Canada.
Int J Gynecol Pathol. 2016 Jul;35(4):385-93. doi: 10.1097/PGP.0000000000000263.
The aim of this study was to compare morphologic assessment and p16 immunohistochemistry (IHC) in the determination of human papilloma virus (HPV) status in vulvar squamous cell carcinoma (VSCC). A total of 201 invasive VSCC cases were classified as "HPV-associated" when warty/basaloid VSCC or high-grade squamous intraepithelial lesion (vulvar intraepithelial neoplasia 2/3) was observed, or "HPV-independent" in the presence of well-differentiated keratinizing invasive SCC or differentiated vulvar intraepithelial neoplasia. For p16 IHC, strong nuclear and cytoplasmic staining of all cells in at least the lowermost third of the epithelium was scored as positive. All cases with discrepant HPV predictions by hematoxylin and eosin morphology versus p16 IHC were further analyzed by polymerase chain reaction for HPV DNA. On the basis of hematoxylin and eosin morphologic assessment, 50/201 tumors showed features suggestive of HPV-associated, and 47 of those showed p16 immunoreactivity (94% concordance). Of the 146 cases considered HPV-independent based on hematoxylin and eosin, 115 (79%) showed negative p16 immunostaining. Thus 83% (162/196) concordance between morphologic assessment and p16 IHC was observed, overall. In 34 cases, where morphologic assessment and p16 IHC did not agree, HPV polymerase chain reaction agreed with p16 IHC in 32/34 (94%). The sensitivity and specificity of p16 IHC in classification of VSCC as HPV-independent or HPV-associated was 100% and 98.4%, respectively. Morphologic assessment and p16 IHC are concordant in classifying VSCC as HPV-independent or HPV-associated in a majority of cases (83%). Most of the discrepant cases are p16-positive well-differentiated keratinizing VSCC, and HPV polymerase chain reaction supports classification of a large majority of these (94%) as HPV-associated. p16 IHC is validated as an accurate surrogate marker for determination of HPV status in VSCC.
本研究的目的是比较形态学评估和p16免疫组化（IHC）在确定外阴鳞状细胞癌（VSCC）中人乳头瘤病毒（HPV）状态方面的作用。共有201例浸润性VSCC病例，当观察到疣状/基底样VSCC或高级别鳞状上皮内病变（外阴上皮内瘤变2/3）时被分类为“HPV相关”，或在存在高分化角化性浸润性鳞状细胞癌或分化型外阴上皮内瘤变时被分类为“HPV非相关”。对于p16 IHC，上皮至少最下三分之一的所有细胞出现强核染色和胞质染色被记为阳性。所有苏木精和伊红形态学与p16 IHC对HPV预测结果不一致的病例，均通过聚合酶链反应进一步检测HPV DNA。基于苏木精和伊红形态学评估，201例肿瘤中有50例表现出提示HPV相关的特征，其中47例表现出p16免疫反应性（一致性为94%）。在基于苏木精和伊红被认为HPV非相关的146例病例中，115例（79%）p16免疫染色为阴性。总体而言，形态学评估和p16 IHC之间的一致性为83%（162/196）。在34例形态学评估和p16 IHC结果不一致的病例中，HPV聚合酶链反应在34例中的32例（94%）与p16 IHC结果一致。p16 IHC在将VSCC分类为HPV非相关或HPV相关时的敏感性和特异性分别为100%和98.4%。在大多数病例（83%）中，形态学评估和p16 IHC在将VSCC分类为HPV非相关或HPV相关方面是一致的。大多数不一致的病例是p16阳性的高分化角化性VSCC，HPV聚合酶链反应支持将其中大多数（94%）分类为HPV相关。p16 IHC被确认为确定VSCC中HPV状态的准确替代标志物。
