阴茎癌中p16免疫组化表达与HPV RNA的差异：一项多重原位杂交/免疫组化方法研究

Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study.

作者信息

Zito Marino Federica, Sabetta Rosalaura, Pagliuca Francesca, Brunelli Matteo, Aquino Gabriella, Perdonà Sisto, Botti Gerardo, Facchini Gaetano, Fiorentino Francesco, Di Lauro Giovanni, De Sio Marco, De Vita Ferdinando, Toni Giorgio, Borges Dos Reis Rodolfo, Neder Luciano, Franco Renato

机构信息

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy.

Department of Pathology, University of Verona, Verona, Italy.

出版信息

Infect Agent Cancer. 2021 Mar 31;16(1):22. doi: 10.1186/s13027-021-00361-8.

DOI:10.1186/s13027-021-00361-8

PMID:33789689

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8011184/

Abstract

BACKGROUND

The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30-50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue.

METHODS

We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC.

RESULTS

The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 - 15 %- versus 6 out of 60 - 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 - 10 %- versus 4 out of 60 - 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity.

CONCLUSIONS

Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.

摘要

背景

高危型人乳头瘤病毒（HPV）感染是阴茎癌发生的主要病因途径之一，约占病例的30%-50%。目前有多种检测HPV的技术，包括基于聚合酶链反应的技术、DNA和RNA原位杂交（ISH）、p16免疫组织化学（IHC）。多重HPV RNA ISH/p16 IHC是一种新技术，可在同一张载玻片上通过单一检测同时检测HPV E6/E7转录本和p16INK4a过表达。本研究的主要目的是评估阴茎癌组织中p16 IHC表达相对于HPV RNA ISH的差异。

方法

我们收集了60例阴茎癌病例。通过RNA ISH、p16 IHC和多重HPV RNA ISH/p16 IHC对HPV进行分析。

结果

该系列中多重HPV RNA ISH /p16 IHC的结果与之前在两张不同载玻片上进行的经典p16 IHC和HPV RNA检测结果完全一致。多重HPV RNA ISH /p16 IHC显示，在我们的系列中，HPV阳性在普通鳞状细胞癌中比在特殊组织学类型中更常见（60例中有19例-15%-，而60例中有6例-10%-），在高级别癌中比在中/低级别癌中更常见（60例中有6例-10%-，而60例中有4例-6.7%-）。此外，我们的数据显示，在20例p16高强度表达的病例中，有5例与HPV RNA ISH阳性无关。

结论

我们的研究结果强调，在我们系列分析的约8%的病例中，使用p16作为HPV阳性的替代指标并不成功。事实上，p16 IHC的敏感性为100%，特异性为71%，阳性预测值（PPV）为54%，阴性预测值为100%；当考虑高强度时，p16 IHC的敏感性为100%，特异性为89%，PPV为75%，NPV为100%。由于HPV阳性可能具有重要的预后和预测价值，这种方法提供的正确特征似乎至关重要。