p27(kip1) expression in rectal cancer correlates with disease-free survival

(1)Background. The cell-cycle inhibitor p27(kip1) is a Potential tumor supp ressor and might serve as a prognostic marker in rectal cancer, in particul ar with regard to patient selection for adjuvant therapy. Materials and methods. Immunohistochemical analysis was performed, using an anti-p27(kip1) monoclonal antibody, on paraffin sections of two matched [a ge, gender, UICC stage, year of operation (1982-1991)] groups of patients ( n = 2 x 82) with rectal carcinoma curatively treated by surgery alone. The groups differed only in subsequent metachronous distant metastatic spread. All patients had to meet the selection criterion "free of local disease," i n order to exclude surgical influence. Follow-up was prospective (median of 74 months). The intensity of staining (-, +, + +, + + +) and rate of posit ive cells (as a percentage of total tumor volume) were judged separately fo r cytoplasms and nuclei. Results. On multivariate analysis, cytoplasmic staining intensity proved to be the best prognostic factor of disease-free survival and approached stat istical significance (P = 0.0552, Cox regression). On univariate analysis, considering cytoplasmic staining alone, intensely stained (+ + +) tumors sh owed significantly poorer disease-free survival (vs + +, +, -; Kaplan-Meier , logrank, P = 0.0185). Conclusions. The demonstrated correlation between cytoplasmic compartmental ization of p27(kip1) and increased metastatic spread as well as disease-fre e survival underscores the role of p27(kip1) in rectal cancer. However, sin ce other reports emphasize the importance of nuclear p27(kip1) expression, the mechanisms of steady-state and subcellular distribution of p27(kip1) re main unclear, and further investigation is needed. (C) 2000 academic press.