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食道扁平上皮癌におけるcyclin D1、cyclin E、cyclin-dependent kinase 4 (CDK4)およびCDK2の異常発現について：松本　学^1,2、降幡睦夫¹、倉林　睦^1,2、園部　宏¹、大朏祐治¹、小越章平²（¹高知医大第二病理、²高知医大第二外）

Deregulated expression of cyclin D1 or cyclin E compared with cyclin-dependent kinase 4 (CDK4) or CDK2 in esophageal squamous cell carcinoma : Manabu MATSUMOTO^1,2, Mutsuo FURIHATA¹, Atsushi KURABAYASHI^1,2, Hiroshi SONOBE¹ Yuji OHTSUKI¹, Shohei OGOSHI² (¹Dept. of Path. II,²Dept. of Surg. II, Kochi Medical School)

Expressions of cyclin D1, cyclin E, CDK4 and CDK2 were immunohistochemically investigated in 90 patients with human esophageal squamous cell carcinoma to determine their significance for the tumor behavior and patientユs prognosis. Nuclear immunostaining of cyclin D1 or cyclin E was observed in 28 (31.1%) or 27 (30.0%), respectively. Thirty nine (43.3%) or 31 tumors (34.4%) were positive in the cytoplasm for CDK4 or CDK2. There was no significant relationship in immunoreactivities between cyclin D1 and CDK4 or cyclin E and CDK2. The simultaneous immunoreactivity of both cyclin D1 and CDK4 was significantly associated with venous invasion (p<0.05). The prognosis of the patient with both cyclin D1 and CDK4 positive tumors was significantly poorer than that with cyclin D1 negative tumors (p<0.05). In a multivariate analysis, both cyclin D1 and CDK4 immunoreactivity (p<0.01) and tumor stage (p<0.001) were recognized as independent risk factors. In addition cyclin D1 positive and CDK4 negative cases, compared with cyclin D1 negative cases showed a poorer survival (p=0.0047). Our in vivo findings suggest that in esophageal SCC, cyclins and CDKs are disorderly overexpressed in many cases and that tumors with simultaneous expression of cyclin D1 and CDK4 shows a worse prognosis. Moreover overexpressed cyclin D1 alone also may contribute to tumor progression independent of CDK4 overexpression.