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Objective: The aim of this study was to investigate the role of matrix metalloproteinase (MMP)-9 protein in high-grade malignant tumors of salivary gland origin as well as its utility as a prognostic marker. Methods: Four micrometer sections from 27 malignant salivary neoplasms were immunostained using a specific antibody against MMP-9. The staining results (proportion of the stained tumor cells and intensity of tumor stainings) were correlated with the clinical data and with patient outcomes. Results: Immunostaining for MMP-9 was observed in 17 cases, predominantly localized in the tumor cells and occasionally in the inflammatory stroma cells. MMP-9 protein expression correlated with N ( P = .04), M ( P = .02), and TNM stages ( P = .03). MMP-9 expression was prognostic for shortened survival ( P = .01). Our results show that the invasiveness and prognosis of high-grade salivary gland cancers may depend on their MMP-9 expression profile. [ABSTRACT FROM AUTHOR]

Background: Among the molecular mechanisms involved in carcinogenesis, defects in the regulation of programmed cell death (apoptosis) make important contributions to the pathogenesis and progression of cancer. Apoptosis regulatory genes include the antiapoptotic bcl-2 gene and the proapoptotic bax gene. The aim of this study was to determine the spectrum of Bax and Bcl-2 expression, and to correlate these findings with clinicopathologic variables and prognosis. Methods: In this study we have evaluated the immunohistochemical expression of Bcl-2 and Bax proteins in a series of 35 squamous cell carcinomas of the tongue. Results: Immunoreactivity for Bax was detected in 37.1% and for Bcl-2 in 8.6% of cells, and for both proteins the staining was cytoplasmic and granular. Bcl-2 and Bax expression was mainly seen in peripheral cells of epithelial tumor islands with decreasing immunoreactivity toward the center of the neoplastic nests. Bax immunoexpression was significantly correlated with histologic grading ( P = 0.05), but not with the remaining clinicopathologic variables. Bcl-2 immunoreactivity was significantly correlated with N-stage ( P = 0.01) and survival. Patients with Bcl-2-negative tumors [mean survival: 73.97 months; 95% confidence interval (CI): 59–88] vs. Bcl-2-positive ones (mean survival: 17.67 months; 95% CI: 6–29) had a longer survival ( P = 0.01; odds ratio = 6.9). Conclusions: Bcl-2 is associated with aggressive disease, neck lymph node metastasis, and poor prognosis. Whereas Bax is related with histologic grade. [ABSTRACT FROM AUTHOR]

Background: Intestinal-type sinonasal adenocarcinoma (ITAC) is an epithelial cancer of the sinonasal sinuses that shows histological similarity to colorectal cancer (CRC) and share chronic inflammation as a possible etiological factor. The Wnt-pathway is one of the most important tumourigenic pathways in CRC. The aim of this study was to investigate if the Wnt-pathway is activated in ITAC., Methodology: Protein expression profiles of E-cadherin, β-catenin, c-myc and cyclin D1 were analysed by immunohistochemistry in 83 samples of ITAC, organized into tissue microarray blocks., Results: Nuclear β-catenin expression was observed in 31% of the cases and was twice as frequent in papillary/colonic ITAC compared to solid/mucinous subtypes. Loss of membranous β-catenin staining occurred in 24% and loss of membranous E-cadherin in 6% of the cases and this was more prominent in mucinous types. Strong c-myc and cyclin D1 expression was observed in 30% and 4% of the cases, respectively. Nuclear β-catenin expression was significantly related to poor clinical outcome, independent from established factors as tumour stage and histological type., Conclusion: The presence of nuclear β-catenin in 31% of patients with ITACs indicated that in a subset of patients, the Wnt-pathway is active and conveys a worse prognosis.

To successfully establish a metastasis from an invasive carcinoma, the first step involves the degradation of the underlying basement membrane, which is mainly made up of type IV collagen. Matrix metalloproteinases (MMPs)-2 and -9 are thought to play an important role in its degradation because of their ability to destroy this type of collagen. In order to evaluate the prognostic significance of these proteases, we studied the expression of MMP-2 and -9 in series of 68 OSCC by immunohistochemistry. Of the oral carcinomas, 28% (n = 19) expressed MMP-2, and 17.6% (n = 12) expressed MMP-9. MMP-2 immunoreactivity was significantly higher in patients with alcohol consumption (p = 0.028) (OR = 4), and in those younger than 60 years (p = 0.041). MMP-9 immunostaining showed statistically significant association with the tumor grade of differentiation (p = 0.019), the T-stage (p = 0.05), and also with the alcohol intake (p = 0.04) (OR = 7.67). In the present study, although not statistically significant, we observed that immunoexpression of MMP-2 and MMP-9 was stronger in patients with lymph node metastasis (OR = 1.65 and 2.29, respectively). In patients without regional lymph node metastasis, positive MMP-9 immunostaining was related to poor survival rates (p = 0.02; OR = 5.8). MMP-2 and -9 are involved in the invasion process of oral cancer, and MMP-9 is related to poor prognosis in the subset of patients without neck node metastasis. Ethanol could enhance the carcinogenetic process in oral cavity through its influence in the expression of MMP-2 and -9.