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人乳头瘤病毒(HPV)阳性、野生型TP53以及p16过表达与肛管鳞状细胞癌放化疗后无残留肿瘤相关。

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma.

作者信息

Soares Paulo C, Abdelhay Eliana S, Thuler Luiz Claudio S, Soares Bruno Moreira, Demachki Samia, Ferro Gessica Valéria Rocha, Assumpção Paulo P, Lamarão Leticia Martins, Ribeiro Pinto Luis Felipe, Burbano Rommel Mario Rodríguez

机构信息

Hospital Ophir Loyola, Belém, Pará, 66060-281, Brazil.

Universidade do Estado do Pará, Belém, Pará, Brazil.

出版信息

BMC Gastroenterol. 2018 Feb 21;18(1):30. doi: 10.1186/s12876-018-0758-2.

Abstract

BACKGROUND

Anal residual tumors are consensually identified within six months of chemoradiotherapy and represent a persistent lesion that may have prognostic value for overall survival. The aim of this study was to evaluate the association of HPV and HIV status, p16 expression level and TP53 mutations with the absence of residual tumors (local response) in Squamous Cell Carcinoma (SCC) of the anal canal after chemoradiotherapy.

METHODS

We performed a study on 78 patients with SCC of the anal canal who submitted to chemoradiotherapy and were followed for a six-month period to identify the absence or presence of residual tumors. HPV DNA was identified by polymerase chain reaction and direct sequencing, HIV RNA was detected by TaqMan amplification, p16 expression was detected by western blotting, and the mutational analysis of TP53 was performed by direct sequencing; additionally, samples carrying mutations underwent fluorescent in sit hybridization. The evaluation of the tumor response to treatment was conducted six months after the conclusion of chemoradiotherapy. The following classifications were used to evaluate the outcomes: a) no response (presence of residual tumor) and b) complete response (absence of residual tumor).

RESULTS

The significant variables associated with the absence of residual tumors were HPV positive, p16 overexpressed, wild-type TP53, female gender, and stages I and II. Only the presence of HPV was independently correlated with the clinical response; this variable increased the chances of a response within six months by 31-fold.

CONCLUSIONS

The presence of HPV in tumor cells was correlated with the absence of a residual tumor. This correlation is valuable and can direct future therapeutic approaches in the anal canal.

摘要

背景

肛门残余肿瘤在放化疗后六个月内得到共识性认定,是一种持续存在的病灶,可能对总生存期具有预后价值。本研究的目的是评估人乳头瘤病毒(HPV)和人类免疫缺陷病毒(HIV)状态、p16表达水平以及TP53突变与肛管鳞状细胞癌(SCC)放化疗后无残余肿瘤(局部反应)之间的关联。

方法

我们对78例接受放化疗的肛管SCC患者进行了一项研究,并随访六个月以确定是否存在残余肿瘤。通过聚合酶链反应和直接测序鉴定HPV DNA,通过TaqMan扩增检测HIV RNA,通过蛋白质免疫印迹法检测p16表达,并通过直接测序进行TP53的突变分析;此外,对携带突变的样本进行荧光原位杂交。在放化疗结束六个月后评估肿瘤对治疗的反应。采用以下分类评估结果:a)无反应(存在残余肿瘤)和b)完全反应(无残余肿瘤)。

结果

与无残余肿瘤相关的显著变量为HPV阳性、p16过表达、TP53野生型、女性性别以及I期和II期。仅HPV的存在与临床反应独立相关;该变量使六个月内出现反应的几率增加了31倍。

结论

肿瘤细胞中HPV的存在与无残余肿瘤相关。这种关联很有价值,可指导未来肛管的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f820/5822520/258212660a7c/12876_2018_758_Fig1_HTML.jpg

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