Lavorato-Rocha André Mourão, Rodrigues Iara Sant'ana, de Melo Maia Beatriz, Stiepcich Mônica Maria Ágata, Baiocchi Glauco, Carvalho Kátia Cândido, Soares Fernando Augusto, Vassallo José, Rocha Rafael Malagoli
Department of Anatomic Pathology, AC Camargo Cancer Hospital, São Paulo, Brazil,
Tumour Biol. 2013 Dec;34(6):3713-20. doi: 10.1007/s13277-013-0955-0. Epub 2013 Jul 6.
Interactions between the cyclin-dependent kinase inhibitors (CDKI) and human papillomavirus (HPV) infection in the pathogenesis of vulvar carcinoma are still incomplete. This study aimed to evaluate the prognostic relevance of these proteins in vulvar cancer. One hundred and thirty-nine patient specimens assembled in a tissue microarray were evaluated for p16, p21, p27, and pRb by immunohistochemistry. HPV status was assessed by a linear array HPV genotyping test. In 16 cases with available frozen tumor, quantitative real-time reverse transcriptase-polymerase chain reaction for CDKN2A(p16), CDKN1A, and Rb was performed. Protein expression was considered positive in 40 patients for p16, 35 for p21, 28 for p27, and 19 for pRb. HPV was positive in 43 of the 105 evaluable cases. Expression of CDKIs and pRb, with the exception of p16, seem to be linked to the early phases of vulvar carcinogenesis. Although p16 and p21 protein expression was associated with early stages of disease, no prognostic significance was found when analyzing CDKI proteins or detecting HPV status, limiting their clinical usage. No association was observed between expression of CDKI proteins and HPV status, suggesting that in spite of this association found in cervical cancer, this seems not to be valid for vulvar carcinoma.
细胞周期蛋白依赖性激酶抑制剂(CDKI)与人乳头瘤病毒(HPV)感染在外阴癌发病机制中的相互作用仍不明确。本研究旨在评估这些蛋白在外阴癌中的预后相关性。通过免疫组织化学对组织芯片中收集的139例患者标本进行p16、p21、p27和pRb评估。通过线性阵列HPV基因分型检测评估HPV状态。在16例有可用冷冻肿瘤的病例中,对CDKN2A(p16)、CDKN1A和Rb进行定量实时逆转录聚合酶链反应。40例患者的p16、35例患者的p21、28例患者的p27和19例患者的pRb蛋白表达被认为呈阳性。105例可评估病例中有43例HPV呈阳性。除p16外,CDKIs和pRb的表达似乎与外阴癌发生的早期阶段有关。尽管p16和p21蛋白表达与疾病早期阶段相关,但在分析CDKI蛋白或检测HPV状态时未发现预后意义,限制了它们的临床应用。未观察到CDKI蛋白表达与HPV状态之间存在关联,这表明尽管在宫颈癌中发现了这种关联,但这在外阴癌中似乎并不成立。