Furihata M, Ohtsuki Y, Sonobe H, Shuin T, Yamamoto A, Terao N, Kuwahara M
Departments of Pathology II and Urology, Kochi Medical School, Nankoku, Kochi 783, Japan.
Clin Cancer Res. 1997 Aug;3(8):1399-404.
Several in vitro studies have shown that cyclin A gene alteration in the cell cycle plays an important role in carcinogenesis. We immunohistochemically examined the expression of cyclin A protein in 120 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter, including adjacent dysplastic lesions to determine their significance for the tumor behavior and patient prognosis. Cyclin A immunostaining of the nucleus was observed in 29 tumors (24.2%). Furthermore, 17 cyclin A-positive tumors (58.6%) had dysplastic lesions positive for cyclin A antibody. The prevalence of cases exhibiting cyclin A staining was higher in the high grade (P < 0.01) and invasive tumors (P < 0.05) than in the other types of tumors. In the selected 117 cases, patients whose TCCs expressed a high level of cyclin A protein had a significantly poorer prognosis than those without cyclin A expression (P < 0.01). These in vivo findings provide the first evidence for frequent and redundant cyclin A protein overexpression in TCC and suggest that cyclin A overexpression is related to the tumor behavior and patient prognosis. In addition, our observations indicate that overexpression of cyclin A may be one of the early events, at least in some cases, in the carcinogenesis of TCC.
多项体外研究表明，细胞周期中的细胞周期蛋白A基因改变在致癌过程中起重要作用。我们采用免疫组织化学方法检测了120例肾盂和输尿管移行细胞癌（TCC）患者，包括相邻发育异常病变中细胞周期蛋白A蛋白的表达情况，以确定其对肿瘤行为和患者预后的意义。在29例肿瘤（24.2%）中观察到细胞核的细胞周期蛋白A免疫染色。此外，17例细胞周期蛋白A阳性肿瘤（58.6%）的发育异常病变对细胞周期蛋白A抗体呈阳性。高级别肿瘤（P<0.01）和浸润性肿瘤（P<0.05）中细胞周期蛋白A染色阳性病例的发生率高于其他类型肿瘤。在所选的117例病例中，TCC表达高水平细胞周期蛋白A蛋白的患者预后明显比无细胞周期蛋白A表达的患者差（P<0.01）。这些体内研究结果首次证明了TCC中频繁且多余的细胞周期蛋白A蛋白过表达，并表明细胞周期蛋白A过表达与肿瘤行为和患者预后有关。此外，我们的观察结果表明，细胞周期蛋白A的过表达可能至少在某些情况下是TCC致癌过程中的早期事件之一。
