Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers
Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers
复制标题
DOI：
10.1177/1010428317706230
复制
发表时间：
2017-05-10
期刊：
影响因子：
--
通讯作者：
Walentowicz-Sadlecka, Malgorzata
中科院分区：
文献类型：
--
作者：
Sadlecki, Pawel;Walentowicz, Pawel;Walentowicz-Sadlecka, Malgorzata
卵巢上皮性肿瘤是一组形态和遗传异质性肿瘤。根据临床表型和遗传背景的差异，卵巢肿瘤分为低级别和高级别肿瘤。交界性卵巢肿瘤约占所有上皮性卵巢肿块的10%-20%。卵巢恶性肿瘤的各种组织学亚型在其危险因素概况、前驱病变、临床病程、扩散模式、分子遗传学、对常规化疗的反应和预后方面有所不同。在低级别浆液性卵巢癌和浆液性交界性肿瘤以及粘液癌中发现的最常见的遗传畸变是BRAF和KRAS基因的突变。最常见的BRAF突变是外显子15中密码子600（V600 E）中的谷氨酸取代缬氨酸。本研究的主要目的是确定是否完全整合，实时聚合酶链反应为基础的Idylla（TM）系统可能是有用的，在确定BRAF基因突变状态的密码子600在卵巢交界性肿瘤和低级别卵巢癌患者。该研究包括42例组织病理学证实的卵巢肿块患者的组织标本，这些患者在比得哥什（波兰）的尼古拉哥白尼大学医学院妇产科接受手术。根据手术标本的组织病理学检查，35个病灶被分类为低度恶性卵巢癌，7个为交界性卵巢肿瘤。使用自动化分子诊断平台Idylla（TM），检测具有BRAF V600 E（VE 1）蛋白表达的样本中BRAF基因的密码子600中的突变。BRAF V600 E（VE 1）蛋白在3例浆液性浅表性乳头状瘤、交界性浆液性乳头状囊腺瘤和部分增殖性浆液性囊腺瘤的胞浆中表达。所有BRAF V600 E（VE 1）蛋白表达的标本均检测出BRAF V600 E/E2/D突变阳性。BRAF V600 E突变的存在与5年生存率之间没有统计学显著关系（p > 0.05）。BRAF突变检测与快速，完全集成的分子诊断系统Idylla（TM）也可能是一个强大的预后工具，在受试者与新诊断的浆液性交界性肿瘤，确定一个子集的患者谁是不太可能进展。
Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla(TM) system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla(TM). Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were tested positively for BRAF V600E/E2/D mutation. No statistically significant relationship (p > 0.05) was found between the presence of BRAF V600E mutation and the probability of 5-year survival. BRAF mutation testing with a rapid, fully integrated molecular diagnostics system Idylla(TM) may be also a powerful prognostic tool in subjects with newly diagnosed serous borderline tumors, identifying a subset of patients who are unlikely to progress.