Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical carcinoma.

Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.

Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma.

Solid tumor cells are known to be highly glycolytic and, to prevent apoptosis by cellular acidosis, cells increase proton efflux through pH regulators, such as monocarboxylate transporters (MCTs). However, the role of these membrane proteins in solid tumor development and survival is not fully understood. We aimed to evaluate the expression of the MCT isoforms 1, 2, and 4 in a large series of cervical lesions (neoplastic and non-neoplastic) and assess its clinical-pathologic significance. The series analyzed included 29 chronic cervicitis, 30 low-grade squamous intraepithelial lesions, 32 high-grade squamous intraepithelial lesions, 49 squamous cell carcinomas, 51 adenocarcinomas, and 30 adenosquamous carcinomas of the uterine cervix. Analysis of the expression of MCT isoforms 1, 2, and 4 was performed by immunohistochemistry with specific antibodies. Immunoreactions were evaluated both qualitatively and semiquantitatively. We found a significant increase in MCT expression from preinvasive to invasive squamous lesions and from normal glandular epithelium to adenocarcinomas. This is the first study evaluating the significance of MCT expression in lesions of the uterine cervix, including invasive carcinomas, and the results found herein led us to believe that these membrane proteins are involved in the progression to invasiveness in uterine cervix carcinoma.

Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix.

OBJECTIVE: We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated. METHODS: We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40. RESULTS: Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells. CONCLUSIONS: Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.