Thymidylate synthase expression, p53, bcl-2, Ki-67 and p27 in colorectal cancer: relationships with tumor recurrence and survival

Gerardo Rosati, Rosistella Chiacchio, Giorgio Reggiardo, Domenico De Sanctis, Luigi Manzione
Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine 2004, 25 (5-6): 258-63
It was the objective to determine in this retrospective study whether thymidylate synthase (TS), p53, bcl-2, Ki-67 and p27 in Dukes' stage B and stage C (AJCC/UICC stage II and III) colorectal adenocarcinoma were predictive of disease-free survival (DFS) and overall survival (OS). Paraffin-embedded specimens from 103 patients with colorectal cancer, treated with surgery between October 1994 and September 1999, were examined for TS expression, p53, bcl-2, Ki-67 and p27 using immunohistochemistry; 51 cases were Dukes' stage B and 52 cases were Dukes' stage C disease. Adjuvant 5-FU-based chemotherapy was given to all patients, while 31 having rectal malignancy also received pelvic radiotherapy. Data were associated with the recurrence rate and survival. With a median follow-up of 5 years, 38 patients (36.8%) developed recurrence and as many patients (36.8%) died. TS was overexpressed in 16 cases (15.6%), p53 nuclear oncoprotein accumulation in >10% of cells occurred more frequently [61 of 103 cases (59.3%)], positive expression of bcl-2 protein in >10% of cells was observed in 41 of 103 cases (39.9%), 57 patients (55.4%) showed immunohistochemical expression of Ki-67 and there were 75 cases (72.9%) with p27 accumulation. The pathological stage was the only independent prognostic factor for DFS (p = 0.042). Sex, as well as age and biological prognostic factors, had no significant impact value on DFS and OS. A multivariate analysis of OS demonstrated that stage C, p53 negative and Ki-67 positive were associated significantly with an unfavorable outcome and a worse median OS (p = 0.035 and t ratio = 2.48). Some biological characteristics such as p53 and Ki-67 status may provide useful prognostic information in addition to the classical clinicopathological parameters. However, further studies are needed to clarify the value of adopting biological prognostic factors into clinical practice.

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