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Int J Radiat Oncol Biol Phys. 2002 Feb 1;52(2):294-303.

Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer.

Author information

1
Department of Radiation Therapy, University of Erlangen, Erlangen, Germany. claus.roedel@strahlen.med.uni-erlangen.de

Abstract

BACKGROUND:

Tumor shrinkage by preoperative radiochemotherapy (RCT) can markedly improve surgery in locally advanced (T4) rectal cancer with clear resection margins and may enable sphincter preservation in low-lying tumors. However, tumor response varies considerably, even among tumors treated according to the same protocol. If one is able to identify patients with highly radio-responsive tumors at the time of diagnosis, a selective and individualized policy of preoperative RCT might be pursued.

METHODS:

The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 44 patients treated uniformly according to a prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Treatment response was assessed histopathologically in the resected surgical specimen, using a five-point grading system. Expression of each marker was correlated with tumor response and relapse-free survival after curative surgery.

RESULTS:

Tumors with complete (n = 3) or good (n = 28) response to RCT showed significantly higher pretreatment levels of apoptosis (mean AI: 2.06%) than tumors with moderate (n = 7), minimal (n = 5), or no regression (n = 1) from RCT (AI: 1.44%, p = 0.003). The AI was significantly related to Ki-67 (p = 0.05), but not to p53 and bcl-2 status. Tumor regression and AI best predicted relapse-free survival after combined modality treatment and curative surgery.

CONCLUSION:

Spontaneous apoptosis in rectal cancer may serve as an important predictor of tumor regression from RCT in rectal cancer and as a significant prognosticator of relapse-free survival. Thus, this molecular marker may finally help to tailor therapy with regard to (neo-) adjuvant treatment of rectal cancer.

PMID:
11872273
DOI:
10.1016/s0360-3016(01)02643-8
[Indexed for MEDLINE]

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