[Prognostic significance and clinic utility of serum and immunohistochemical cathepsin B levels in colorectal cancer].
BACKGROUND
Aproximately one third of node-negative colorectal cancer recur suggesting the presence of micrometastasis not detected by conventional histopathologic methods. We think that the role of enzymes like Cathepsin B play in the process of invasion and metastasis in colorectal cancer might identify at earlier stages patients with high risk of shorter survival and who need more aggressive treatment. Our porpuse is to evaluate the prognostic significance of preoperative serum and inmunohistochemical levels of cathepsin B to identify colorectal carcinomas with worse prognostic.


METHODS
Fifty five patients undergoing surgical treatment for colorectal cancer from 1998 to 2000. As a control group sera from 23 patients with acute appendicitis. Serum levels of cathepsin B were obtained preoperatively (KRKA, Novo Slovenia;ng/ml); cathepsin B inmunoreactivity was determinated after surgical treatment, (C-19, Santa Cruz Biotechnology). Serum levels of CEA (Inmulit 2000 CEA), and CA 19,9 (Inmulite Gi-Ma, Diagnostic Products Corporation, Los Angeles, CA), and p53 expression (Dako) were determinated in patients with colorectal cancer. Survival analysis was realized using Cox and Kaplan-Meier methods (SPSS 10.0 for Windows).


RESULTS
The mean age of patients with colorectal cancer was 68 years (range 39-87 years). 29 males and 26 females. Tumor size was 4.6 cms., range 1-12. Rectal localization, 32.2%. Moderately differentiated, 49.1%. The median serum and inmunohistochemical levels of cathepsin B were 5.74 ng/ml and 29.56% in patients with acute appendicitis respectively. Preoperative serum levels in patients with colorectal cancer were: CEA, 46.04 ng/ml (range 0.21-7.32 ); CA 19,9, 110.52 UI/ml, (range 2.5-1920); and Cathepsin B, 6.94 ng/ml, range 3.57-11.6). Inmunohistochemical results were: p53, 44.36%, (range 0-95); Cathepsin B, 66.9% (range 10-90). Serum and inmunhistochemical values were significantly increased in patients with colorectal cancer when compared with control group, p=0,011 and p=0,000. High serum levels of cathepsib B were significantly associated wiyh shorter survival of patients with colorectal cancer in univariate and multivariate methods, p=0.041;HR 1.281 95%CI (1.043-1.716) and p= 0.022; HR 1.338.955 CI (1.043-1.716).


CONCLUSIONS
Cathepsin B can be used like an independent prognostic tumoral marker in colorectal cancer. Preoperative serum levels over 6.94 ng/ml, are associated with worse prognostic and shorter survival.
Servicio de Cirugía General y del Aparato Digestivo. Complejo Hospitalario de Ciudad Real. Spain. maynona@terra.es
D
D
Padilla
T
T
Cubo
J M
JM
Molina
M
M
García
G
G
De la Osa
T
T
Palomino
R
R
Pardo
J
J
Martín
E
E
Arévalo
J
J
Hernández Calvo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002401:Cathepsin B / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D002401:Cathepsin B