SummaryThe p27 Kip1 gene has been identified as inductor of cell cycle arrest at the G1 checkpoint to prevent entry of somatic cells into the S phase of the cell cycle when substantial DNA damage has occurred. It has been suggested that decreased expression of the p27 Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms. In the present study, 95 specimens (T1-T4) from 95 randomly selected patients undergoing radical prostatectomy at the Urological Department of Hannover University (82 patients) as well as in the Josef Hospital Regensburg (13 patients) between 1981 and 1992 for whom tissue blocks for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as possible predictors for recurrence-free and long-term survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as decreased expression of the p27 Kip1 protein. After a median follow-up up of 56 months (24-151 months), seven of 21 (33%) patients (Group 1) with loss of p27 Kip1 protein expression or a relative amount of <10% of positively stained tumour cells developed recurrent disease in contrast to 17 of 74 (23%) patients (Group 2) with retained p27 Kip1 protein expression (≥10% of positively stained tumour cells). The median recurrence-free survival was 14 months (5-40 months) for patients from Group 1 and 31 months (7-133 months) for Group 2 patients (P = 0.02). In multivariate analysis, loss of p27 Kip1 protein expression was identified as the only independent prognostic parameter for recurrence-free survival. In contrast, neither the univariate nor the multivariate analysis showed a correlation between loss of p27 Kip1 protein expression and the long-term survival of the patients. Prospective studies are urgently needed to confirm the independent prognostic value of decreased p27 Kip1 protein expression together with overexpression of the p53 tumour suppressor protein in patients with localized prostate cancer. The availability of more refined prognostically important biological variables in addition to established prognostic factors like tumour stage or Gleason score might help decision making in patients at high risk for the development of local recurrence or systemic tumour progression. © 1999 Cancer Research Campaign Keywords: prostate cancer; prognosis; p27 Kip1 gene 1052British Journal of Cancer (1999) 81(6), 1052-1058 © 1999 Cancer Research Campaign Article no. bjoc.1999 Received 10 cell cycle arrest at the G1 checkpoint by a negative regulatory influence on cyclins and cdks . Recently, a heat stable 27 kDa protein, the transcript of the p27 Kip1 gene that has been mapped on chromosome 12p12.3 (Martin et al, 1995), has been suggested to substantially participate in cell cycle control by preventing entry of somatic cells into the S phase of the cell cycle (Craig et al, 1997). p27 Kip1 , first identified in extracts of tumour growth factor β (TGF-β)-treated cells as an inhibitor ...
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