Maranchie J K, Bouyounes B T, Zhang P L, O'Donnell M A, Summerhayes I C, DeWolf W C
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
J Urol. 2000 Mar;163(3):748-51.
We present preliminary clinical, histochemical and molecular findings for 5 patients with micropapillary transitional cell carcinoma of the bladder, a rare histological variant not widely recognized in the urological literature.
The 5 patients were prospectively identified. In 3 cases immunohistochemical staining for expression of CD31, p53, E-cadherin, and alpha, beta and gamma-catenin was performed on paraffin embedded tissue. Sequencing was used to identify point mutations in exons 5 to 9 of p53, and exons 1 and 2 of H-ras.
Of the patients 2 died within 1 year of presentation to our institution with rapid local extension along the bladder serosal surface and ureteral sheaths. Another patient had progression to invasive disease within 22 months. In the 3 cases with immunohistochemical staining p53 was negative, despite positive staining of nonmicropapillary transitional cell carcinoma within the same specimen. Stains for the angiotrophic marker CD31 were negative. In all 3 cases normal membrane associated alpha, beta and gamma-catenin expression was present. Examination of p53 sequences revealed a single point mutation in exon 8 of 1 case. In 2 cases different mutations in exon 1 of H-ras were noted.
Micropapillary transitional cell carcinoma is a rare and highly aggressive variant. Paradoxically, our study demonstrated no significant p53 abnormalities. The lacunar histological pattern did not appear to represent invasion of vascular spaces. Rather, these tumors seemed to have the ability to disrupt and replace the normal stromal matrix to achieve rapid nonendothelial extension. Thus, micropapillary histology may predict a lesser likelihood of surgical cure.
我们展示了5例膀胱微乳头移行细胞癌患者的初步临床、组织化学和分子学研究结果，这是一种在泌尿学文献中未被广泛认识的罕见组织学变体。
前瞻性地确定了这5例患者。对3例患者的石蜡包埋组织进行了CD31、p53、E-钙黏蛋白以及α、β和γ连环蛋白表达的免疫组织化学染色。采用测序法鉴定p53外显子5至9以及H-ras外显子1和2中的点突变。
在这些患者中，2例在就诊于我院1年内死亡，肿瘤沿膀胱浆膜表面和输尿管鞘迅速局部扩散。另1例患者在22个月内进展为浸润性疾病。在3例进行免疫组织化学染色的病例中，尽管同一标本中的非微乳头移行细胞癌呈阳性染色，但p53为阴性。血管生成标记物CD31染色为阴性。在所有3例病例中，均存在正常的膜相关α、β和γ连环蛋白表达。对p53序列的检测发现1例患者外显子8有一个单点突变。在2例病例中，注意到H-ras外显子1有不同的突变。
微乳头移行细胞癌是一种罕见且侵袭性很强的变体。矛盾的是，我们的研究未发现明显的p53异常。腔隙性组织学模式似乎并不代表血管间隙浸润。相反，这些肿瘤似乎有能力破坏并取代正常的基质，以实现快速的非内皮性扩展。因此，微乳头组织学可能预示手术治愈的可能性较小。
