Molecular and clinico-pathological markers in rectal cancer: a tissue micro-array study.
OBJECTIVE
The aims of the study were to study the effect of pre-operative treatment on the expression of tumour-related proteins and to correlate the expression of these proteins with response and survival of patients with advanced rectal cancer.


METHODS
Tissue micro-arrays from pre- and post-treatment biopsies of 99 patients with rectal cancer treated with pre-operative (chemo)radiotherapy were stained for epidermal growth factor receptor (EGFR), carbonic anhydrase IX, Ki67, vascular endothelial growth factor, cyclo-oxygenase 2 (COX-2) and cleaved cytokeratin 18 (c-CK18). Also, fibro-inflammatory alterations after treatment were evaluated.


RESULTS
Pre-operative (chemo)radiotherapy caused fibro-inflammatory changes, a downregulation of proliferation (Ki67) and EGFR and an upregulation of apoptosis (cleaved CK18). Patients with a good regression during pre-operative treatment showed less proliferating and apoptotic cells in the resection specimen. Multivariate analysis showed that T downstaging, fibro-inflammatory changes in the resection specimen and COX-2 expression in the biopsy correlated with overall survival.


CONCLUSIONS
Pre-operative treatment has an effect on proliferation, apoptosis, inflammation and EGFR expression. The classical clinical parameters as well as fibro-inflammatory changes and COX-2 expression seem most valuable as predictors for survival.
Debucquoy
Annelies
A
Department of Radiation Oncology, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. Annelies.debucquoy@med.kuleuven.be
Goethals
Laurence
L
Libbrecht
Louis
L
Perneel
Christiaan
C
Geboes
Karel
K
Ectors
Nadine
N
McBride
William H
WH
Haustermans
Karin
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D016000:Cluster Analysis; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D053538:Keratin-18 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012074:Remission Induction; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D053538:Keratin-18; D019394:Ki-67 Antigen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D066246:ErbB Receptors