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Annals of Oncology Advance Access originally published online on July 29, 2008
Annals of Oncology 2008 19(12):2026-2032; doi:10.1093/annonc/mdn428
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

gastrointestinal tumors

Preoperative radiochemotherapy is successful also in patients with locally advanced rectal cancer who have intrinsically high apoptotic tumours

M. J. E. M. Gosens1,2, R. C. Dresen1, H. J. T. Rutten1,*, G. A. P. Nieuwenhuijzen1, J. A. W. M. van der Laak2, H. Martijn3, I. Tan-Go4, I. D. Nagtegaal2, A. J. C. van den Brule4 and J. H. J. M. van Krieken2

1 Department of Surgery, Catharina Hospital, Eindhoven
2 Department of Pathology, Radboud University Medical Centre, Nijmegen
3 Department of Radiotherapy, Catharina Hospital, Eindhoven
4 Department of Pathology, Pathological Anatomy and Medical Microbiology Laboratories, Eindhoven, The Netherlands

* Correspondence to: Dr. H. J. T. Rutten, Catharina Hospital, Michelangelolaan 2, PO Box 1350, Eindhoven, The Netherlands. Tel: +31-40-2397164; Fax: +31-40-2443370; E-mail: harm.rutten{at}cze.nl

Background: Not all patients with locally advanced rectal cancer (LARC) respond equally to neo-adjuvant radiochemotherapy (RCT). Patients with highly apoptotic less advanced rectal cancers do not benefit from short-term radiotherapy. This study investigates whether this is also the case in the setting of RCT for LARC.

Patients and methods: Tissue microarrays were constructed of biopsy and resection specimens of 201 LARC patients. Apoptosis (M30) and several apoptosis-regulating proteins [p53, Bcl-2, Bax, cyclooxygenase-2 (Cox-2) and mamma serine protease inhibitor (maspin)] were studied with immunohistochemistry. Subsequently, predictive values for local recurrence (LR), overall survival (OS) and histological tumour regression were analysed.

Results: Apoptotic levels, quantified as the number of apoptotic cells/mm2 tumour epithelium, were higher in posttherapy tissues compared with biopsies (P < 0.001). Biopsies from clinical T4 stage tumours demonstrated significantly higher levels of apoptosis than clinical T3 stage tumours (P = 0.020). Therapy-induced apoptosis was higher when the interval between the last day of irradiation and surgery increased (P < 0.001, correlation coefficient = 0.355). Pre- and posttherapy apoptosis, p53, Bcl-2, Bax and Cox-2 were not associated with LR, OS or tumour regression. Intense pretherapy cytoplasmatic staining of maspin indicated a higher risk on LR (P = 0.009) only.

Conclusion: Combined RCT is also successful in highly apoptotic tumours and is therefore independent of intrinsic apoptosis.

Key words: apotosis, locally advanced rectal carcinoma, radiochemotherapy

Received for publication April 23, 2008. Revision received June 17, 2008. Accepted for publication June 18, 2008.


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