Resumo:
Two separate experiments were performed using bitches with mammary carcinoma to evaluate the
expression of VKINA in the tumor microenvironment and its possible correlation with the
lymphocytic response and disease outcome in bitches with malignant mammary tumors. In the
first experiment, 65 bitches were divided into four groups: control (CG: n=13), mammary
carcinomas (CM: n=12), carcinomas in mixed tumors (CMT: n=33), and carcinosarcomas (CSS:
n=7). The patients underwent clinical and laboratory evaluation, mastectomy, clinical-pathological
characterization of the tumor, morphology of the inflammatory infiltrate, immunohistochemistry
with VKINA staining, and immunophenotyping of peripheral blood and tumors by flow cytometry,
in addition to survival analysis. The results indicate that in malignant mammary tumors of bitches
there is an intratumoral predominance of TCD4+
lymphocytes about TCD8+
lymphocytes. In
contrast, tumors with higher expression of TCD8+ presented a better prognosis. High expression
of VKINA (≥120) directly correlated with histological grading and TGFβ+ but cannot yet be
considered an independent prognostic marker. In conclusion, high expression of VKINA (≥120)
may interfere with tumor aggressiveness, and the study of its interactions may help in
understanding its immunomodulatory capacity, especially in different histological types, bringing
new prognostic and therapeutic perspectives, both for female dogs and for women. In the second
experiment, a total of 46 female dogs were selected and divided into three groups: control (GC:
n=13), CMT grade I (CMT I: n=22), and CMT grade II/III (CMT: n=11). The patients underwent
clinical and laboratory evaluation, mastectomy, clinical-pathological characterization of the tumor,
morphology of the intratumoral inflammatory infiltrate, immunophenotyping of peripheral blood
and tumors by flow cytometry, and assessment of VKINA by immunohistochemistry, in addition
to survival analysis. The results indicated that the mesenchymal component associated with the
myxoid matrix contributes to higher grading, nodal metastasis, and lower survival in MSC, IL12
possibly helps CMT I in tumor combat, the most aggressive tumors (grade II/III) presented greater
infiltration of TCD4+
and TGF-β
+
, and expression of VKINA in the extracellular matrix. Thus, it
is suggested that MSC has a characteristic microenvironment depending on its degree of
aggressiveness. The mesenchymal component, the high expression of TGFβ+
, and VKINA
influence tumor aggressiveness, while IL12 in CMT I helps in tumor combat. This is the first study
to show the relationship between VKINA and IL12 and TGFβ+
in this histological subtype.
