Furihata M, Ohtsuki Y, Sonobe H, Shuin T, Yamamoto A, Terao N, Kuwahara M
Department of Pathology II, Kochi Medical School, Nankoku, Japan.
Br J Cancer. 1998 Mar;77(5):783-8. doi: 10.1038/bjc.1998.127.
Cyclin E gene alteration in the cell cycle plays an important role in carcinogenesis, while p53 protein affects different phase checkpoint pathways by activating p21WAF1/CIP1 in the normal cell cycle. We immunohistochemically examined the expression of cyclin E and p53 proteins in 121 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter to determine their significance for tumour behaviour and patient prognosis. Cyclin E and p53 immunostaining of the nucleus was observed in 36 tumours (29.8%) and 35 tumours (28.9%) respectively. A significant percentage, 69.4% (25 out of 36 tumours), of the cyclin E-positive tumours exhibited simultaneous labelling for p53 (P < 0.05). Mirror-section technique was performed in five selected double-positive tumours to identify cancer cells that were nuclei positive for both cyclin E and p53. The prevalence of cases simultaneously exhibiting both cyclin E and p53 immunostaining was higher in the high-grade tumours (P < 0.01) than in the other types of tumours. Patients with TCCs coexpressing cyclin E and p53 had a significantly poorer prognosis than those expressing neither cyclin E nor p53 (P < 0.001). These in vivo findings provide evidence for cyclin E protein overexpression in TCCs intimately associated with p53 alteration and suggest that simultaneous overexpression of both cyclin E and p53 is related to tumour behaviour and poor prognosis.
细胞周期中的细胞周期蛋白E基因改变在致癌过程中起重要作用，而p53蛋白在正常细胞周期中通过激活p21WAF1/CIP1影响不同阶段的检查点途径。我们采用免疫组织化学方法检测了121例肾盂和输尿管移行细胞癌（TCC）患者中细胞周期蛋白E和p53蛋白的表达，以确定它们对肿瘤行为和患者预后的意义。分别在36例肿瘤（29.8%）和35例肿瘤（28.9%）中观察到细胞核的细胞周期蛋白E和p53免疫染色。在细胞周期蛋白E阳性肿瘤中，有69.4%（36例中的25例）同时显示p53标记（P<0.05）。对5例选定的双阳性肿瘤进行了镜像切片技术，以识别细胞周期蛋白E和p53细胞核均为阳性的癌细胞。高级别肿瘤中同时出现细胞周期蛋白E和p53免疫染色的病例发生率高于其他类型肿瘤（P<0.01）。同时表达细胞周期蛋白E和p53的TCC患者的预后明显比既不表达细胞周期蛋白E也不表达p53的患者差（P<0.001）。这些体内研究结果为TCC中与p53改变密切相关的细胞周期蛋白E蛋白过表达提供了证据，并表明细胞周期蛋白E和p53同时过表达与肿瘤行为和不良预后有关。
