Espressione immunoistochimica di mast cell tryptase, macrophage marker, CD79a, IgA, IgG e IgM nei tumori delle ghiandole epatoidi e della ghiandola mammaria nel cane

According to the "field of the organization of tissues" (Toft) theory, cancer arises from deregulated interactions between cells and their stromal microenvironment. Immune cells that infiltrate tumors play decisive roles at different stages of tumor development. Among the most common canine neoplasms, the tumors of perianal glands are characterized by a mild aggressive biological behavior despite the malignancy; on the contrary canine mammary tumors are very aggressive and often metastatize. Aim of this work is to contribute to the knowledge of the canine hepatoid gland tumors and canine mammary tumors through the assessment of stromal immune cell such as macrophages, plasmacells and mast cells. The immunohistochemical expression for Mast cell Tryptase, Macrophage Marker, CD79 on 25 cases of hepatoid gland tumors (10 of Adenoma and 15 of Carcinoma) and on 43 cases of mammary lesions (10 hyperplasia, 10 simple carcinoma, 5 solid carcinoma , 8 micropapillary carcinoma and 10 cases of mixed carcinoma) was performed. Each sample was tested by immunofluorescence assay to evaluate the expression of IgG, IgA and IgM. Based on the obtained results, immunofluorescence and immunohistochemistry for anti-CD 79 antibody were carried out. Cell markers revealed the number and localization of plasmacells (PC), mast cells (MC) and macrophages (MA). In the hepatoid gland the number of macrophages and plasma cells increased in benign lesions and progressively decreased in carcinomas, while the number of mast cells was low in all the samples. In addition, in hyperplasia/adenoma CD79 epithelial positive cells were found inside the glandular lobules. Positive epithelial cells were scattered in carcinomas and epitheliomas. Anti-canine IgA, IgM and IgG were localized in PC and hepatoid cells in hyperplastic/adenomatous and cancerous cells. Conversely in the mammary gland the number of plasmacells and macrophages decreased in hyperplastic areas, conversely characterized by the high presence of mast cells; in the malignant lesions, above all in peritumoral stroma, a mild increase in MCs number and a high increase in the number of MA and PC were observed. Rare cells were detectable in the intratumoral stroma. An intense positivity to IgA and IgG was also detected, while the positivity for IgM was weak or absent. Moreover, the positivity for the antibody anti Cd79a, both at immunofluorescence and immunohistochemistry, was located in the basal cells of the solid tumors and in glandular cells of simple and micropapillary carcinomas. Stromal immune components support cancer initiation, progression and metastasis. We found an increased number of MC, PC and MA in neoplastic lesions of hepatoid gland and mammary gland. Moreover, we found Immunoglobulins (Igs) and CD79 both in neoplastic hepatoid glands and canine mammary tumors. Immunoglobulins, known also as antibody, traditionally are considered as an exclusive product of B cells. These molecules recognize and neutralize pathogens and other cells considered "non-self". They play a crucial role in the regulation of the immune system mechanisms. Noteworthy, in the last decades, has been highlighted that many physiological and pathological “non B” cells, including epithelial cells, gametes, endothelial cells, cardiomyocytes and neurons may also express Igs (i.e., IgA, IgG and IgM). Even if several authors demonstrated the presence of Igs in human epithelial tumor, the role of these molecules and their clinical significance in the development of oncological disease it is still unknown as well as their eventual use in the therapeutic approach to cancer remains to be explored. CD79 and Igs have been found in human cancerous cells and their role in cancerogenesis has being raising interest in recent years. On the basis of our preliminary results and literature data, we suggest that such cells and molecules could have a role in local immune responses and could be directly involved in the biology of hepatoid gland tumor. Anti-canine IgA and IgM immunofluorescence revealed positivity of hepatoid cells both in hyperplastic/adenomatous and cancerous cells. Immunoglobulin and CD79 immunostain are strongly suggestive of the involvement of hepatoid glands in local defensive mechanism of the skin yet their role in cancer progression should not be excluded. Overall, the obtained data showed that research need to be more addressed to understand the function of hepatoid gland and the biology of hepatoid gland tumor. The presence of IgA, IgG and IgM has been demonstrated in the woman breast cancer and several scientific evidences underline the correlation between the expression of these molecules and the proliferation or the regression of the cancer. The Igs expressed by breast cancer, as well as other epithelial tumors, may be used as a prognostic and therapeutic cancer marker. In fact, recently, in humans the cancer immunotherapy has been investigated by several groups of researchers. Numerous studies investigate the production of monoclonal antibodies as a potential personalized therapy for cancer. These monoclonal antibodies are active against both tumor and stromal microenvironment. The present study investigate the expression of Immunoglobulins (IgG, IgA and IgM) in the neoplastic epithelium of dog mammary glands. The result herein reported on Ig positivity, are consistent with those stated for the woman breast cancer. Therefore a canine tumor, already recognized as a study model in comparative oncology, represents an important support, also, for the study of innovative treatments such as personalized immunotherapy.