Expression of caveolin-1 in mucoepidermoid carcinoma of the salivary glands: correlation with vascular endothelial growth factor, microvessel density, and clinical outcome.
BACKGROUND
Caveolin-1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The importance of caveolin-1 in endothelial cells in angiogenesis has been confirmed. The clinicopathologic significance of caveolin-1 expression and its correlation with angiogenesis remains unknown in mucoepidermoid carcinoma (MEC) of the salivary glands.


METHODS
Based on an immunohistochemical study, the expression levels of caveolin-1 and vascular endothelial growth factor (VEGF) and the intratumoral microvessel density (MVD) (labeled by CD34) in 75 patients with MEC were investigated, and correlations with clinicopathologic variables were evaluated statistically.


RESULTS
The expression rates of both caveolin-1 and VEGF were 54.7% (41 of 75 tumors). MVD varied from 9 to 56 (24.45 +/- 10.72)/x 200. Caveolin-1 expression was correlated inversely with duration of tumor, clinical stage, histologic grade, and MVD (P = .027, P = .011, P = .04, and P = .025; respectively). VEGF expression was associated positively with MVD (P = .000). Advanced clinical stage, higher grade, and tumors that originated from minor salivary glands exhibited higher MVD (P = .029, P = .002, and P = .008, respectively). The presence of clinical symptoms, male gender, advanced clinical stage, higher grade, increased MVD, and down-regulated caveolin-1 were correlated significantly with the development of recurrent disease, as indicated by a shorter disease-free interval (P < .05). Both univariate and multivariate analyses indicated that clinical stage, histologic grade, and MVD were independent prognostic factors (P < .05). The presence of clinical symptoms and the down-regulation of caveolin-1 were identified as negative prognostic predictors in the univariate analysis (P < .05) but did not achieve significance in the multivariate analysis (P > .05).


CONCLUSIONS
The current results suggest that caveolin-1 may function as a tumor suppressor in MEC of the salivary glands. Reduced expression of caveolin-1 and increased MVD may indicate a poor prognosis for certain patients.
Shi
Lu
L
Key Laboratory for Oral Biomedical Engineering, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Chen
Xin-Ming
XM
Wang
Li
L
Zhang
Lu
L
Chen
Zhi
Z
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018277:Carcinoma, Mucoepidermoid / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis*; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012468:Salivary Gland Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D051242:Caveolin 1; D042461:Vascular Endothelial Growth Factor A