Identificação de fenótipos moleculares e sua relação com fatores clínico-patológicos, tratamento e sobrevida em neoplasias mamárias caninas

Abstract

Establishing the prognosis in female dogs with mammary neoplasms is a great challenge because it is influenced by several clinical and pathological factors. In medicine the molecular classification of breast neoplasms of women is recommended by the International Consensus of Breast Cancer Specialists - St. Gallen. Considering that the use of the St Gallen System, as recommended in human medicine, has not yet been used for the molecular classification of canine mammary neoplasms, the objective of the present study was to characterize the immunophenotype of these neoplasms according to the classification of St Gallen. Thus, an immunohistochemical panel for RE, RP, Ki67, HER2, CK5/6 and EGFR was used to define the immunophenotypes in 170 malignant mammary neoplasms and defined subtypes: luminal A (32%), luminal B HER2- (51%), luminal B HER2 + (5%) and triple negative (12%). A better prognosis was associated to the luminal A subtype in relation to the other immunophenotypes, this subtype was also associated with the initial clinical stage (I-III) and higher frequency of carcinomas in mixed tumors. While solid carcinoma and micropapillary carcinoma were associated with the Luminal B HER2- subtype. Luminal B HER2 + was the subtype of worse prognosis with shorter survival time and higher risk of death. In the second stage of the present study, we aimed to evaluate the expression of RE, RP, Ki67 and COX-2 for the definition of immunoprogntic subtypes with implications for the therapeutic response. The evaluation of RE/RP, Ki67 and COX2 in 130 breast neoplasms of female dogs allowed to define a better prognosis associated with neoplasms with RE / R positivity, Ki67 20% and high score of COX-2 and RE / RP-, Ki67> 20% and high COX-2 score. The study demonstrated that the different immunophenotypes have implications for the prognosis of female dogs with malignant mammary cancers. The luminal subtypes were predominant, and the luminal B HER2 + subtype was described for the first time and a better prognosis was associated with luminal A. The coordinated evaluation of RE/RP, Ki67 and COX2 markers in canine mammary neoplasms contributes to categorize patients in different immunoprognostic groups and to select patients who will benefit from adjuvant therapies.