Predictive value of decreased p27(Kip1) protein expression for the recurrence-free and long-term survival of prostate cancer patients

The 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 d evelopment of human malignancies due to lass of critical antiproliferative mechanisms. In the present study, 95 specimens (T1-T4) from 95 randomly sel ected patients undergoing radical prostatectomy at the Urological Departmen t of Hannover University (82 patients) as well as in the Josef Hospital Reg ensburg (13 patients) between 1981 and 1992 for whom tissue blocks for immu nohistochemical investigation were available, were investigated for differe nt biological and clinical characteristics as possible predictors for recur rence-free and long-term survival: age, depth of tumour infiltration, histo logical grade, lymph node status, as well as decreased expression of the p2 7(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 express ion or a relative amount of <10% of positively stained tumour cells develop ed recurrent disease in contrast to 17 of 74 (23%) patients (Group 2) with retained p27(Kip1) protein expression (greater than or equal to 10% of posi tively stained tumour cells), The median recurrence-free survival was 14 mo nths (5-40 months) for patients from Group 1 and 31 months (7-133 months) f or Group 2 patients (P = 0.02). In multivariate analysis, loss of p27(Kip1) protein expression was identified as the only independent prognostic param eter for recurrence-tree survival. In contrast, neither the univariate nor the multivariate analysis showed a correlation between loss of p27(Kip1) pr otein expression and the long-term survival of the patients. Prospective st udies are urgently needed to confirm the independent prognostic value of de creased p27(Kip1) protein expression together with overexpression of the p5 3 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 developm ent of local recurrence or systemic tumour progression. (C) 1999 Cancer Res earch Campaign.