TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Acta Obstetricia et Gynecologica Scandinavica Pub Date : 2023-10-15 DOI:10.1111/aogs.14689

Harsh Nitin Dongre, Rammah Elnour, Stian Tornaas, Siren Fromreide, Liv Cecilie Vestrheim Thomsen, Ingrid Benedicte Moss Kolseth, Elisabeth Sivy Nginamau, Anne Christine Johannessen, Olav Karsten Vintermyr, Daniela Elena Costea, Line Bjørge

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引用次数: 0

Abstract

Introduction

Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways—one involving high-risk human papilloma virus infection (HPV-associated), and the other without HPV infection (HPV-independent) often involving TP53 mutation. HPV-associated VSCC generally has a better progression-free survival than HPV-independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC.

Material and methods

Immunohistochemistry for p53, Ki67 and p16^INK4A (a surrogate marker for HPV infection) was performed on formalin-fixed paraffin-embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi-square test and multivariable Cox regression model were used to investigate the association of different parameters with progression-free survival and disease-specific survival (DSS), and Kaplan–Meier curves were used to show the association of different parameters with survival.

Results

The results of p53 and p16^INK4A immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression-free survival (p = 0.024) after adjustment for FIGO stage. p16^INK4A immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression-free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders.

Conclusions

p53 and p16^INK4A immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.

Abstract Image

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TP53突变和人类乳头状瘤病毒状态是挪威外阴鳞状细胞癌队列中的独立预后因素。

引言：外阴鳞状细胞癌（VSCC）通过两种不同的分子途径发展，一种涉及高危人类乳头状瘤病毒感染（HPV相关），另一种不涉及HPV感染（HPV无关），通常涉及TP53突变。与HPV无关的VSCC相比，HPV相关的VSCC通常具有更好的无进展生存率。本研究的目的是在123名VSCC患者的回顾性队列中，使用免疫组织化学方法确定TP53突变状态，比较不同的HPV检测方法，并与生存率相关。材料和方法：p53的免疫组织化学，Ki67和p16INK4A（HPV感染的替代标志物）在福尔马林固定的石蜡包埋组织上进行检测，以鉴定VSCC的分子亚型。通过HPVDNA PCR和HPVMRNA原位杂交（ISH）检测是否存在HPV感染。Pearson卡方检验和多变量Cox回归模型用于研究不同参数与无进展生存率和疾病特异性生存率（DSS）的相关性，Kaplan-Meier曲线用于显示不同参数与生存率的相关性。结果：p53和p16INK4A免疫组化结果证实了三种VSCC亚型与不同的预后相关。TP53突变状态被确定为无进展生存率较差的独立预后因素（p = 0.024）。p16INK4A免疫组织化学、mRNA ISH和DNA PCR在HPV检测方面具有极好的一致性。根据多变量Cox回归模型，hrHPV mRNA的存在与无进展生存率的增加显著相关（p = 0.040）和DSS（p = 0.045）。结论：p53和p16INK4A免疫组织化学将VSCC队列分为三种亚型，其中TP53突变的患者预后最差。ISH检测hrHPV mRNA是提高生存率的独立预测指标。因此，p53和HPV mRNA的联合检测可能改善VSCC的风险分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Obstetricia et Gynecologica Scandinavica 医学-妇产科学

CiteScore

8.00

自引率

4.70%

发文量

180

审稿时长

3-6 weeks

期刊介绍： Published monthly, Acta Obstetricia et Gynecologica Scandinavica is an international journal dedicated to providing the very latest information on the results of both clinical, basic and translational research work related to all aspects of women’s health from around the globe. The journal regularly publishes commentaries, reviews, and original articles on a wide variety of topics including: gynecology, pregnancy, birth, female urology, gynecologic oncology, fertility and reproductive biology.