p53, Bcl-2 and Ki-67 Expression according to Tumor Response after Concurrent Chemoradiation Treatment for Advanced Rectal Cancer

Kim, Nam Kyu; Park, Jae Kyun; Yang, Woo Ik; Yun, Seong Hyeon; Sung, Jin Sil; Min, Jin Sik

Abstract

PURPOSE: Concurrent chemoradiation treatment (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but its tumor response shows wide spectrum. The aim of study is to investigate any correlation between a related genetic mutations, proliferative index and tumor response after CCRT.
METHODS
A twenty three patients with rectal cancer, which preoperatively staged as over T3N1 or T4 determined by transrectal ultrasonography and MRI. Enrolled patients were given 5 FU 450 mg/m2 and leucovorin 20 mg/m2 intravenously for 5 days during the first and fifth weeks of radiation therapy (45~54 Gy). 4 weeks after completion of scheduled treatment, surgical resection was performed. Tumor response was classified into CR (complete remission), PR (partial response: 50% of diminution of tumor volume and downstaging), NR (no response). Paraffin-embedded tissues obtained before chemoradiation treatment were studied with immunohistochemical staining of p53, Bcl-2 and Ki-67. The extent of tumor response was correlated with proliferative activity as measured by immunostaining of Ki-67 proliferative antigen and expression of p53 and bcl-2 oncoproteins (less than 10%: negative, 10~25%: , 25~50%: , more than 50%: , Ki-67: to count a labeled cells per 1,000 cells).
RESULTS
All patients were resectable. CR was obtained in 4 (17.4%), PR in 10 (43.3%) and NR in 9 (39.2%). p53 mutation was noted in 16 (70%). p53 mutation was found in NR: 5 (31.3%), PR: 9 (56.2%), CR: 2 (12.5%), respectively. Bcl-2 expression was noted in 11 (48%). NR as in 4 (36.3%), PR: 3 (28.4%) and CR: 4 (36.3%), respectively. Ki-67 labeling index was NR: 615.4 446.2, PR: 663.2 296.4, CR: 765.5 188.3, respectively (CR PR Vs NR, p=0.029).
CONCLUSIONS
Immunohistochemical Expression of p53 and bcl-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be useful parameters for good radiosensitive tumor selected for CCRT.