| In mammals, the cell division cycle is governed directly by cyclin -dependent kinases (cdks). The cdks are controlled by a variety of regulatory proteins, including cyclins, kinases and phosphatases, and cdk inhibitors. p27Kip1 is a cdk inhibitor that regulates cell cycle progression from the Gl phase to the S phase by binding to the cyclin E/ cdk2 complex, there by inhibiting this kinase. In vivo studies have demonstrated that mice lacking p27Kip1 have an increased body size associated with hyperplasia of multiple organs and a high incidence of pituitary tumors, suggesting that p27 Kip1 plays a general role in regulating cell growth and may be a potential tumor suppressor gene. Although intensive investigations have indicated that the p27Kip1 mutation is a rare event in human carcinomas, loss of p27Kip1 expression or down - regulation of p27Kip1 proteins induced by increased protenase degradation have been shown in common human carcinomas of the breast, colorectum, prostate, and lung. The expression level of p27Kip1 has been revealed to be correlated inversely with rumor cell progression and has proved to be an independent prognostic predictor in the aforementioned carcinomas.Ductal adenocarcinoma of the pancreas is a lethal disease, with ffew reports of 5 - year survivors, and, what is worse, the incidencehas been reported to be gradually increasing during the past few decades worldwide. Although surgical extirpation for localized tumors offers the only chance of a cure, the majority of patients die of their disease within 2 years of surgery. The identification of prognostic factors would provide not only an optimal treatment option but also a guide in developing novel therapeutic strategies for this lethal disease. To explore whether the loss or altered expression of p27Kip1 correlates with the outcomes of patients with pancreatic adenocarcinoma, an investigation using the anti - p27Kip1 antibody, along with an assessment of tumor cell proliferation by S - P immunostaining, was conducted on 36 resected specimens of this disease, including 1 patients with cystade-nocarcinomas and 3 patients with mucinproducing carcinomas. We have found that loss of p27Kip1 expression independently predicts a poor prognosis for patients with pancreatic adenocarcinomas.Materials and MethodsA total of 36 patients with pancreatic adenocarcionmas who underwent wurgical resection with curative intent in the Department of General Surgery of Chinese Medical university from 1993 to February 2000 were involved in this study. The original clinical and pathologic materials for all eases were reviewed, including histologic sections stained with hematoxylin and eosin. The histologic type, status of lymph node metastasis, peripancreatic invasion, and disease stuage were determinde in accordance with the General Rules for the Study of Pancreatic Cancer by the Japan Pancreas Society. The tumor sizes measured from the resected specimens was grouped as either 2. 0 cm or >2.0 cm in greatest dimension. Tumor cell differentiation was re-classified as well, moderate, or poor according to the TNM classification. There were 23 males and 13 females, and the mean age of the patients was 60.0 years (standard deviation, 11.3 years; range, 30 - 79 years). Of 36 patients, 1 patients were diagnosed with cystaden - carcinomas, and 3 patients were diagnosed with mumin - producing carcinomas. Surgeries in 13 patients were defined as curability C because of microscopic posityive findings within 10 mm of resection margins of either peripancreatic soft tissue (12 patients) or pancreas (1 patient). 11 Three patients, including one with mumin -producing carcinoma who died of surgical complications, were excluded from the survival analysis. The mean value of follow - up intervals was 25 months, with a median of 13 months (range, 2 -120 months). None of the patients received any evaluable adjuvant therapy.Immunohistochemical Staining for p27Kip1 Protein and Ki -67 Antigen.The level of p27Kip1 protein in each case was evaluated originally...
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