Expressão imuno-histoquímica de C-kit e detecção de Intern Tandem Duplications no Exon 11 em melanomas caninos cutâneos e da cavidade oral

Abstract

C-Kit is a transmembrane receptor tyrosine kinase, and is encoded by the KIT gene. It has already been shown that c-Kit participates in carcinogenic processes in several neoplasias, presenting aberrant expressions and, sometimes, mutations in the KIT gene. Among the c-Kit mutations already described, the ITDs stand out for culminating with the constitutive activation of the protein in some neoplasias, thus acquiring an importance in the development of target therapies for the treatment of some types of tumors. The expression of c-Kit and mutations in their respective gene have already been identified in different types of melanoma, but their mechanism of action in this neoplasia still lacks future investigations, both in humans and in different animal species. Thus, this work aimed to evaluate the immunohistochemical expression of c-Kit and its correlation with the histopathological features of oral and cutaneous canine melanomas such as the identification of ITD-like mutations in exon 11 of the KIT gene. We used 80 cases of melanoma (26 oral and 54 cutaneous), fixed in formaldehyde and included in paraffin blocks, selected from the collection of the Comparative Pathology Laboratory of UFMG. Protein expression of c-Kit was assessed by immunohistochemistry for CD117 (Polyclonal), correlating its results with tumor histopathological characteristics and the cell proliferation index obtained by immunohistochemistry for Ki-67 (MIB- 1). The identification of ITD-like polymorphisms in exon 11 was evaluated by means of the conventional PCR technique. About 35% of melanomas were positive for c-Kit. In cutaneous cases, there was a positive correlation between immunohistochemical evaluations for c-Kit with cell proliferation (Ki-67 expression), a fact that was not observed among the oral cases. Regarding the research of ITD mutations, no sample presented such alteration. Thus, it is concluded that, although present in both oral and cutaneous melanomas in dogs, c-Kit plays a differentiated role in each type of tumor, and may be closely related to cellular proliferation in cutaneous tumors. Moreover, the absence of ITD mutations in these samples does not rule out the lack of other gene mutations, which, therefore, should be investigated with a purpose to understand their role in the development of this neoplasm and generate possible therapeutic targets.