Yin Hui, He Qun, Li Ting, Leong Anthony S-Y
Department of Pathology, Genitourinary Institute, First Hospital of Peking University, Beijing, China.
Appl Immunohistochem Mol Morphol. 2006 Sep;14(3):260-5. doi: 10.1097/00129039-200609000-00002.
Urothelial carcinoma in situ (CIS) is a high-grade neoplasm and an indicator of recurrence and progression that requires specific treatment. The distinction of CIS from flat non-neoplastic urothelium, in particular dysplasia, on the basis of histologic features is often difficult, and this study aims to validate cytokeratin 20 (CK20) and Ki-67 as discriminatory markers for this purpose. Immunostaining of these markers was applied to 26 cases of CIS, 14 atypia of unknown significance, 4 dysplasia, 6 normal, and 9 hyperplastic urothelium. CIS showed CK20 staining of deep urothelial cells in 23/26 CIS compared with restricted staining in surface cells in all non-neoplastic lesions. CIS had significantly increased Ki-67 index with a mean of 53.37% compared with that of non-neoplastic urothelium, which was <10% (P<0.0001). The proliferating cells were distributed randomly in CIS, whereas in non-neoplastic urothelium, staining was confined to the basal layer. Among the cases of atypia, 3/14 displayed deep staining for CK20 and 6/14 had elevated Ki-67 counts. In dysplasia similar findings were present in 1/4 and 2/4 cases, respectively. These findings suggest that CK20 and Ki-67 are objective markers to distinguish CIS from non-neoplastic urothelium. In cases of "atypia of unknown significance" and "dysplasia," positivity for both markers should raise the possibility of CIS or preneoplastic change and identify those cases for follow-up.
原位尿路上皮癌（CIS）是一种高级别肿瘤，是复发和进展的指标，需要特殊治疗。基于组织学特征将CIS与扁平非肿瘤性尿路上皮，尤其是发育异常相区分往往很困难，本研究旨在验证细胞角蛋白20（CK20）和Ki-67作为用于此目的的鉴别标志物。将这些标志物的免疫染色应用于26例CIS、14例意义不明的异型性、4例发育异常、6例正常和9例增生性尿路上皮。与所有非肿瘤性病变表面细胞的局限染色相比，23/26例CIS的深层尿路上皮细胞显示CK20染色。CIS的Ki-67指数显著升高，平均为53.37%，而非肿瘤性尿路上皮的Ki-67指数<10%（P<0.0001）。增殖细胞在CIS中随机分布，而在非肿瘤性尿路上皮中，染色局限于基底层。在异型性病例中，14例中有3例显示CK20深染，14例中有6例Ki-67计数升高。在发育异常中，分别有1/4和2/4的病例有类似发现。这些结果表明，CK20和Ki-67是区分CIS与非肿瘤性尿路上皮的客观标志物。在“意义不明的异型性”和“发育异常”病例中，两种标志物呈阳性应增加CIS或肿瘤前改变的可能性，并识别出那些需要随访的病例。
