High tumor grade in salivary gland mucoepidermoid carcinomas and loss of expression of transforming growth factor beta receptor type II.
BACKGROUND
Mucoepidermoid carcinoma (MEC) of salivary glands is a malignant, locally aggressive neoplasm with metastatic potential. The clinical course is usually dependent on histology; however, low-grade carcinomas can result in metastases and tumor-related death. Transforming growth factor beta1 (TGF-beta1) is a potent cytokine that affects growth inhibition of various cells and stimulates extracellular matrix production and angiogenesis. Loss of TGF-beta receptor type II (TGF-beta RII) expression has been related to resistance of TGF-beta1-mediated growth control and tumor progression. In this study, we correlate MEC tumor grade with expression of TGF-beta1 and TGF-beta RII.


METHODS
Immunohistochemical staining was performed on 16 MEC specimens for activated forms of TGF-beta1 and TGF-beta RII. The percentage of cells in which staining yielded positive findings for activated TGF-beta1 and TGF-beta RII was correlated with tumor grade.


RESULTS
Activated TGF-beta1 was detected in 16 specimens (100%) of MEC and showed strong positive and diffuse staining. Predominately cytoplasmic staining of TGF-beta1 was seen in salivary gland ducts, stroma, and endothelial cells. There was an inverse correlation between tumor grade and loss of expression of TGF-beta RII. All low-grade MEC tumors yielded positive staining results, whereas only one case of intermediate-grade MEC had TGF-beta RII expression. No high-grade MEC showed TGF-beta RII expression.


CONCLUSIONS
Loss of expression of TGF-beta RII correlates with tumor grade. The localization of activated TGF-beta1 within neoplastic epithelium, tumor-associated stroma, and endothelium suggests that it might play a role in the stromal proliferation and/or angiogenesis associated with MEC.
Dillard
D G
DG
Department of Pathology and Laboratory Medicine, 1364 Clifton Rd NE, Atlanta, GA 30322, USA.
Muller
S
S
Cohen
C
C
Bloch
D
D
Del Gaudio
J M
JM
Gal
A A
AA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018277:Carcinoma, Mucoepidermoid / Q000473:pathology*; D004727:Endothelium / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010307:Parotid Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D013365:Submandibular Gland Neoplasms / Q000473:pathology; D014062:Tongue Neoplasms / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II