Determination of molecular marker expression can predict clinical outcome in colon carcinomas.
OBJECTIVE
Conventional staging procedures are often unable to precisely predict prognosis in colorectal cancer (CRC). In this study, we set out to investigate the possible role of molecular/structural indicators involved in cell cycle regulation (p27 and p53), apoptosis (p53 and p27), and tumor neoangiogenesis [p53, vascular endothelial growth factor (VEGF), and microvessel count] in predicting tumor behavior and clinical outcome in CRC patients


METHODS
Analysis of the above indicators was performed by immunohistochemistry on 104 CRC patient samples and 25 normal colon mucosa specimens.


RESULTS
Intense p27 nuclear staining was found in normal colon mucosa, with p53 nuclear staining and VEGF cytoplasmic accumulation <10%, and low microvessel count. In contrast, in CRC samples, p27 was down-regulated in 53.8%, p53 protein was overexpressed in 52%, and VEGF stained positive in 67.3% of the cases, respectively. Multiple regression analysis showed that molecular markers were strongly correlated. In patients treated with curative surgery, a significant relationship was seen between p27 down-regulation and Dukes' stage, nodal status, and the presence of distant metastases. VEGF overexpression correlated significantly with Dukes' stage, tumor (t) and metastasis (m) parameters, and left site. Stepwise regression selected p27, p53, VEGF, and Dukes' stage as the best combination of variables capable of predicting both disease-specific and disease-free survival.


CONCLUSIONS
The investigated indicators may be useful for the prediction of outcome and recurrence rate in curatively treated CRC patients. In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging alone and help better select therapeutic options in CRC patients.
Galizia
Gennaro
G
Division of Surgical Oncology, Second University of Naples School of Medicine, Naples, Italy. gennaro.galizia@unina2.it
Lieto
Eva
E
Ferraraccio
Francesca
F
Orditura
Michele
M
De Vita
Ferdinando
F
Castellano
Paolo
P
Imperatore
Vincenzo
V
Romano
Ciro
C
Ciardiello
Fortunato
F
Agostini
Bruno
B
Pignatelli
Carlo
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D050760:Cyclin-Dependent Kinase Inhibitor p27