Vail Eric, Zheng Xiaoyong, Zhou Ming, Yang Ximing, Fallon John T, Epstein Jonathan I, Zhong Minghao
Department of Pathology, Westchester Medical Center, New York Medical College, Valhalla, NY, USA.
NYU Medical Center, New York, NY, USA.
Ann Diagn Pathol. 2015 Oct;19(5):301-5. doi: 10.1016/j.anndiagpath.2015.06.007. Epub 2015 Jun 16.
Glandular lesions of the urinary bladder include a broad spectrum of entities ranging from completely benign to primary and secondary malignancies. The accurate diagnosis of these lesions is both important and challenging. Recently, studies suggest that telomerase reverse transcriptase (TERT) promoter mutations could be a biomarker for urothelial carcinoma (UC). We hypothesized that these mutations can distinguish UC with glandular differentiation from nephrogenic adenoma, primary adenocarcinoma of the urinary bladder (PAUB), or secondary malignancies. Twenty-five cases of benign glandular lesions (including nephrogenic adenoma); 29 cases of UC with glandular differentiation; 10 cases of PAUB; and 10 cases each of metastatic colon cancer, prostatic carcinoma, and carcinoma from Mullerian origin were collected. Slides were reviewed and selected to make sure the lesion was at least 10% to 20% of all tissue. Macrodissection was performed in some of cases, and genomic DNA was extracted from the tissue. Telomerase reverse transcriptase promoter mutations were determined by standard polymerase chain reaction sequencing. Twenty-one cases (72%) of UC with glandular differentiation were positive for TERT promoter mutations. However, none of the remaining cases (total 65 cases of benign lesions, PAUB, and metastatic carcinomas) was positive for TERT promoter mutation. Telomerase reverse transcriptase promoter mutations were highly associated with UC including UC with glandular differentiation but not other glandular lesions of bladder. Therefore, in conjunction with morphologic features, Immunohistochemistry stain profile, and clinical information, TERT promoter mutations could distinguish UC with glandular differentiation from other bladder glandular lesions. In addition, lack of TERT promoter mutations in primary adenocarcinoma of bladder suggests that this entity may have different origin or carcinogenesis from those of UC.
膀胱的腺性病变包括一系列广泛的实体，范围从完全良性到原发性和继发性恶性肿瘤。准确诊断这些病变既重要又具有挑战性。最近，研究表明端粒酶逆转录酶（TERT）启动子突变可能是尿路上皮癌（UC）的生物标志物。我们假设这些突变可以将具有腺性分化的UC与肾源性腺瘤、膀胱原发性腺癌（PAUB）或继发性恶性肿瘤区分开来。收集了25例良性腺性病变（包括肾源性腺瘤）；29例具有腺性分化的UC；10例PAUB；以及各10例转移性结肠癌、前列腺癌和苗勒氏源性癌。对玻片进行复查和筛选，以确保病变至少占所有组织的10%至20%。部分病例进行了宏观解剖，并从组织中提取了基因组DNA。通过标准聚合酶链反应测序确定端粒酶逆转录酶启动子突变。21例（72%）具有腺性分化的UC的TERT启动子突变呈阳性。然而，其余病例（总共65例良性病变、PAUB和转移性癌）均无TERT启动子突变呈阳性。端粒酶逆转录酶启动子突变与包括具有腺性分化的UC在内的UC高度相关，但与膀胱的其他腺性病变无关。因此，结合形态学特征、免疫组织化学染色谱和临床信息，TERT启动子突变可以将具有腺性分化的UC与其他膀胱腺性病变区分开来。此外，膀胱原发性腺癌中缺乏TERT启动子突变表明该实体可能与UC具有不同的起源或致癌机制。
