Pinheiro Céline, Longatto-Filho Adhemar, Ferreira Luísa, Pereira Sônia Maria Miranda, Etlinger Daniela, Moreira Marise A R, Jubé Luiz Fernando, Queiroz Geraldo Silva, Schmitt Fernando, Baltazar Fátima
Life and Health Sciences Research Institute ICVS, School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.
Int J Gynecol Pathol. 2008 Oct;27(4):568-74. doi: 10.1097/PGP.0b013e31817b5b40.
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.
已知实体瘤细胞具有高度糖酵解特性,并且为了通过细胞酸中毒来防止细胞凋亡,细胞会通过pH调节剂(如单羧酸转运蛋白(MCTs))增加质子外流。然而,这些膜蛋白在实体瘤发生和存活中的作用尚未完全明确。我们旨在评估一系列宫颈病变(肿瘤性和非肿瘤性)中MCT亚型1、2和4的表达情况,并评估其临床病理意义。分析的病例系列包括29例慢性宫颈炎、30例低级别鳞状上皮内病变、32例高级别鳞状上皮内病变、49例鳞状细胞癌、51例腺癌以及30例宫颈腺鳞癌。采用特异性抗体通过免疫组织化学法对MCT亚型1、2和4的表达进行分析。对免疫反应进行了定性和半定量评估。我们发现从浸润前鳞状病变到浸润性鳞状病变,以及从正常腺上皮到腺癌,MCT表达显著增加。这是第一项评估MCT表达在包括浸润性癌在内的宫颈病变中的意义的研究,本文的研究结果使我们相信这些膜蛋白参与了宫颈癌向浸润性发展的过程。