[Proliferation and apoptosis before and after preoperative simultaneous radiochemotherapy of rectal carcinomas].
OBJECTIVE
To investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p53 in rectal cancer before and after radiochemotherapy.


METHODS
Thirty-two patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biopsies and the final resected specimens after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected after radiochemotherapy.


RESULTS
After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased when comparing biopsies and resected specimens. Tumors that were immunohistochemically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging.


CONCLUSIONS
Our results indicate, that radiochemotherapy induces an increase in apoptotic cell death. The observation of higher rates of apoptosis in p53 negative tumors suggests that p53 might be a regular of apoptosis in rectal cancer.
Tannapfel
A
A
Institut für Pathologie, Universität Leipzig.
Nüsslein
S
S
Katalinic
A
A
Köckerling
F
F
Wittekind
C
C
Fietkau
R
R
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007262:Infusions, Intravenous; D019394:Ki-67 Antigen / Q000032:analysis; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012007:Rectum / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D005472:Fluorouracil
Proliferation und Apoptose vor und nach präoperativer simultaner Radiochemotherapie von Rektumkarzinomen.