Based on the results, it is observed that the frequency of these kind of tumors in dogs in the records of the Pathology Department in the Faculdade de Medicina Veterinária e Zootecnia - USP, from 1936 to 1999 is variable, as well as the expression of the extracellular matrix in 578 these different histological types of carcinomas and benign neoplasms .The percentile of benign tumors (7.09 %) is novel information, for it was not found in the specialized literature studied 11,12. The justification may be attributed to the fact that the authors, in general, have used a small universe for the determination of the number of cases. Non-neoplasic proliferative lesions have been observed in only 1 % of the 1,371 cases studied, information that was not found in the literature. In relation to histogenesis, 98% of 1,249 malignant tumors were carcinomas. The other 2 % were mesenchymal tumors in the tissue of the mammary gland: osteosarcomas (19%), chondrosarcomas (9%), fibrosarcomas (67%) and liposarcoma (5%). Among the 537 different histological types of malign neoplasms reclassified, however, 7 cases were fibrosarcoma (1.30%), 1 chondrosarcoma (0.18%) and 1 osteosarcoma (0.18%) In relation to this, it may be inferred that myoepithelial cells are responsible for condroblast and osteoblast tumors, and may also be transformed in chondrosarcomas and osteosarcomas. Fibroblasts and lipoblasts, on the other hand, when undergoing malignant transformation would generate, respectively, fibrosarcomas and liposarcomas . In the series of observations performed in the present trial, carcinosarcomas were not considered, for the origin of the altered cells is myoepithelial and not fibroblastic 5,17. Simple and complex mammary carcinomas were present in 65% and 35 % of the cases, respectively.
Mammary neoplasms frequently present an abundant amount of extracellular matrix, which is called desmoplasia. It could be noted, from the analysis of carcinomas and benign neoplasms in relation to the presence of desmoplasia, that complex tubular adenocarcinoma presented it more frequently (38%). The lower frequency was found in anaplastic carcinoma (14%). Desmoplasia is increased in mammary carcinomas probably as a result of the secretion, by the tumoral cells, of factors known as mesenchymal cell biosynthetic activity modulators, such as TGFb , TGFa , PDGF, FGF23,18,10; due to the secretion of a 68 kDa polypeptide which increases collagen synthesis in other cells, including fibroblasts4 and other biosynthesis products from tumoral cells which modulate the renewal of ECM macromolecules responsible for the regulation of the synthesis or degradation, or both. This altered matrix, in its turn, may influence several tumoral functions such as morphology13,14,15 differentiation, binding, metastasis potential and biosynthesis activity9. This altered matrix would act on myoepithelial cells, which, in their turn, would have a paracrinous effect on glandular epithelium, regulating tumor progression and accumulating, more than degrading, the ECM (they present low expression of proteinases and high expression of proteinase inhibitors). These cells also contribute for the synthesis of basal membrane, inhibit angiogenesis and express a great amount of maspim, a tumor suppresser21 . In mammary neoplasms, desmoplasia may occur due to the action of tumoral and myoepithelial cells. According to21, myoepithelial cells, besides their contractile function and their role in the synthesis and remodeling of basal membrane, may also regulate growth, differentiation and morphogenesis of neighboring, epithelial and mesenchymal cells, for they secrete growth factors and cytokines such as TGFb , TGFa and interleukin6. With the increase of gene instability, from tubular adenocarcinoma to anaplastic carcinoma, epithelial cells would secrete a larger quantity of these modulators for matricial cells, which may cross the physical barrier presented by basal membrane, leading to the loss in myoepithelial cells suppressing characteristics or even to their transformation. In anaplastic carcinomas, where there is a low frequency of desmoplasia, these two cell types are so phenotipically altered that the paracrine effect of myopithelial cells over the other cells would not restrain proliferation, invasion and metastatization of the transformed epithelial cells any longer.
In relation to the presence of cartilaginous and bone metaplasia, it was noted that tubular adenocarcinoma was the type of tumor that presented them most frequently: 57 % of cartilaginous metaplasia and 28 % of bone metaplasia.
Among benign tumors, cystic papillary fibroadenoma presented the major frequency of cartilaginous metaplasia (50%). No bone metaplasia was observed in this kind of tumor. The higher frequency of bone metaplasia among benign tumors was found in the adenomas (13.05%). In 1974, Bomhard and Sanderselben6, in a ultrastructural study, demonstrated the presence of condroitin sulfate in myoepithelial cells and Araí et al.1,2,3, demonstrated that the distribution of collagen type II and type IX in the ECM with cartilaginous metaplasia was similar to that of normal hyaline cartilage and to collagen type IX, detected in mammary myoepithelial cells when they begin to proliferate near the basal membrane. In these initial stages, myoepithelial cells do not present characteristics of condrocytes or expressed collagen type II and XI. According to Araí et al.1, collagen type IX precociously detected only in the cytoplasm of myoepithelial cells and not in the extracellular matrix, may have an important role in the initial stages of condrometaplasia as a proliferation promoter. It may be, thus, used as an excellent cell marker for progenitor cells in myoepithelial cells related to chondrometaplasia. The expression of collagen XI enables the expression of collagen II and IX. Besides, in order to clarify the suppressing action of myoepithelial cells, it is known that the phenotypic expression of tumor suppresser genes may be due to the high homology between complementary DNA and aminoacid sequence of the suppresser gene and that of collagen type II and IX specific of chondrocytes. Myoepithelial cells express TGFb and other members of the TGFb family such as bone morphogenetic proteins, including osteogenin and osteogenic proteins know as bone / cartilage inducing factors19.
It may be inferred from information found in the specialized literature, that the expected higher frequency of chondro and osteometaplasia is related to complex type tumors, benign and more differentiated, for the increase in gene instability in neoplasic cells during the progression of tumors and their influence on myoepithelial cells would make them lose their suppressing activity.