Gap junctions are the only communicating junctions found in animal tissues and are composed of
proteins known as
connexins. Alterations in
connexin expression have been associated with
oncogenesis; reported studies in rodent and human mammary glands, which normally express
connexins 26 and 43, confirm these alterations in
malignancies.
Mammary neoplasms represent the second most frequent
neoplasm in dogs, and since there are no reports on the study of
connexins in canine mammary glands, the present study investigated the expression of
connexins 26 and 43 in normal, hyperplastic, and neoplastic mammary glands of this species, to verify if altered patterns of
connexin staining are related to higher cell proliferation and malignant phenotypes. A total of 4 normal, 8 hyperplastic mammary glands, 9 benign, and 51 malignant mammary gland
neoplasms were submitted for the immunostaining of
connexins 26 and 43,
E-cadherin, and
proliferating cell nuclear antigen (
PCNA). Normal, hyperplastic, and benign neoplastic mammary glands showed a punctate pattern for
connexin 26 and 43 staining and an intercellular
E-cadherin staining.
Malignant neoplasms, especially the most aggressive cases with high cell proliferation rates, presented either fewer gap junction spots on the cell membranes or increased cytoplasmic immunostaining. Malignant
tumors also expressed a less intense immunostaining of
E-cadherin; the expression of this adhesion molecule is important for the transportation of
connexins to cell membranes and in forming communicating gap junctions. Deficient expression of
E-cadherin could be related to the aberrant
connexin localization and may contribute to the malignant phenotype. In conclusion, the expression and distribution of
connexins and
E-cadherin are inversely correlated to cell proliferation in malignant
mammary neoplasms of dogs and may well be related to their more aggressive histologic type and
biologic behavior.