Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression.
BACKGROUND
Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis.


METHODS
Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P < .05. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test.


RESULTS
Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04).


CONCLUSIONS
Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.
Department of Pathology, School of Medicine, CEGIN-BIOREN, Universidad de La Frontera, Temuco, Chile.
Patricia
P
Garcia
Pamela
P
Leal
Hector
H
Alvarez
Priscilla
P
Brebi
Carmen
C
Ili
Oscar
O
Tapia
Juan C
JC
Roa
D002764:Cholecystitis / Q000378:metabolism / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D046888:Tissue Array Analysis
C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor