P27(kip1) expression is associated with tumor response to preoperative chemoradiotherapy in rectal cancer

Background: Our aim was to ascertain whether or not the response to preoper ative chemoradiotherapy for rectal cancer is associated with p27(kip1) and p53 protein expression. Methods: Thirty-eight patients (27 male, 11 female) with a mean age of 59 y ears (age range 33-87) and stage II-ID: rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m(2)/day and leucovorin 10 mg/m (2)/day). Thirty-one underwent low anterior resection; seven underwent abdo minoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitot ic index, and p27(kip1) and p53 protein expression which were immunohistoch emically determined. p53 expression was graded as: a) absent or present in less than or equal to 10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in > 75% of tumor cells, p27(kip1) expression was assessed using both light microscopy (percent of stained cells x10 HPF) an d cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (co mplete pathologic response). Results: The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases, p53 protein expression was foun d in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells e xpressing the p27(kip1) protein was 34 (range 0-77.14%). A close correlatio n was found between cytometric and light microscopy findings for p27(kip1) (r(2) = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor i n 2 cases, and moderate in the remaining 31 cases. While the response to ad juvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor i n 13 (34.21%) cases. Univariate analysis associated type of adjuvant therap y (chemoradiotherapy, P = .0428) and p27(kip1) protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regres sion found overexpression of p53 and p27(kip1) and young age to be independ ent variables that were linked to a good response to adjuvant therapy. Conclusions: Lack of p27(kip1) and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.