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From the Departments of Surgery (NKK, JKP, KYL, SHY, JSM), Pathology (WIY), and Radiation Oncology (JS), Yonsei University College of Medicine, Seoul, Korea.
Correspondence: Address correspondence and reprint requests to: Nam Kyu Kim, MD, Department of Surgery, Yonsei University College of Medicine, Seodamun-Gu, Shinchon-dong 134, CPO 8044, Seoul, Korea; Fax: 822-313-8289; E-mail: namkyuk{at}yumc.yonsei.ac.kr
Background: Concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but tumors show wide spectrum response. The purpose of this study was to investigate any correlation among related genetic mutations, proliferative index, and tumor response after CCRT.
Methods: This study included 23 patients with rectal cancer, who were preoperatively staged as at least T3 N1 or T4 (determined by transrectal ultrasonography and MRI). Enrolled patients were given 5-FU 450 mg/m2/day and leucovorin 20 mg/m2/day intravenously for 5 days during weeks 1 and 5 of radiotherapy (45–54 Gy). Surgical resection was performed 4 weeks after completion of the scheduled treatment. Tumor response was classified as CR (complete response), PR (partial response: 50% diminution of tumor volume and downstaging), and NR (no response). Paraffin-embedded tissue obtained before chemoradiotherapy was studied by immunohistochemical staining for p53, BCL-2, and Ki-67. The extent of tumor response was correlated with proliferative activity and was measured by immunostaining Ki-67 proliferative antigen and the expression of p53 and BCL-2 oncoproteins.
Results: All patients were resectable. CR was obtained in 4 patients, PR in 10 patients, and NR in 9 patients. The p53 mutation was noted in 16 patients: NR in 5 patients, PR in 9 patients, and CR in 2 patients (P = .638). BCL-2 expression was noted in 11 patients: NR in 4 patients, PR in 3 patients, and CR in 4 patients (P = .799). The Ki-67 labeling index was NR: 615.4 ± 47.2; PR: 663.2 ± 20.4; and CR: 765.5 ± 58.3 (CR + PR vs. NR, P = .029).
Conclusions: Immunohistochemical expression of p53 and BCL-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be a useful parameter for radiosensitive tumors selected for CCRT.
Key Words: Rectal cancer • Preoperative chemoradiotherapy • Tumor response • p53 • BCL-2 • Ki-67
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