p53 protein overexpression and response to induction chemoradiation therapy in patients with locally advanced rectal adenocarcinoma.

The association between mutations in the p53 gene and prognosis in colorectal cancer remains controversial. This report evaluates the role of p53 protein to predict the response of neoadjuvant chemoradiation therapy in patients with primary locally advanced rectal adenocarcinoma. Between January 1993 and December 1994, 26 patients were seen with locally advanced primary rectal adenocarcinoma, located between 0 and 10 cm from the anal verge, demonstrated clinically and by CT scan. Each received 45 Gy of preoperative radiation therapy (RT) concomitantly with bolus infusion of 5-fluorouracil (5-Fu) (450/mg/m2 on days 1 to 5 and 28 to 33 of RT). Surgery was performed between 4 and 8 weeks later. All the primary tumors were mapped and sliced. The response rate was divided according to the percentage of malignant cells in the rectal wall and perirectal fat. Lymph nodes were studied with the manual or modified clearing technique. p53 mutant status was assessed immunohistochemically from sections of the formalin-fixed, paraffin-embedded pretreatment biopsy and the resected specimen. There were 14 females and 12 males, with a mean age of 54 years. All received the scheduled treatment. An abdominoperineal resection (n = 10), low anterior resection (n = 10), and pelvic exenteration (n = 6) were performed. The stages of tumors were as follows: no residual tumor (n = 4); T2 (n = 6); T3-4 (N = 9); and T3-4, N1,2 (n = 7). Fourteen specimens (54%) had mutated p53, and 10 (71%) had >50% of residual tumor, whereas only two (17%) of the specimens with normal p53 had >50% of residual tumor (P = .018). Eight of the 10 low anterior resections were performed in patients whose specimens expressed normal p53. Our results suggest that the determination of p53 is a factor in predicting tumor response in patients who undergo preoperative chemoradiation therapy for rectal adenocarcinoma.