Lymphatic microvessels density, VEGF-C, and VEGFR-3 expression in 25 cases of breast invasive lobular carcinoma.

Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer, having distinct morphologically but also prognostic and therapeutic features. This type of breast cancer shows a higher rate of multiple metastases with a more frequent axillary-lymph-node involvement. Related to these dissemination and metastatic features, we aimed to study the immunohistochemical expression of D2-40, VEGF-C and VEGFR-3 in 25 cases of ILCs stratified according to the histopathological and molecular classification. Regardless of histopathological or molecular subtype, the statistical tests proved that for ILC, the highest D2-40 lymphatic microvessels density (LMVD) was in the peritumoral areas. In classical subtype, the LMVD values were positively correlated with the degree of tumor differentiation and pTNM clinical stages and when these cases were classified based on the molecular criteria the highest recorded values were found in the luminal B subtype. In addition, regardless of the histopathological and molecular subtypes, the D2-40 LMVD varied in the same direction for both VEGF-C and VEGFR-3 categories, with the highest LMVD values recorded in those cases with the highest VEGF-C and VEGFR-3 reactivity, especially in the peritumoral areas. Considering only the molecular luminal A and B subtypes, we have noted that VEGF-C and VEGFR-3 expression was significantly higher in luminal A subtype compared to luminal B. This immunoprofile suggests the existence of a tumor type-specific lymphangiogenesis that may have certain prognostic and therapeutic implications.

The involvement of growth differentiation factor 5 (GDF5) and aggrecan in the epithelial-mesenchymal transition of salivary gland pleomorphic adenoma.

Pleomorphic adenoma is the most common salivary gland tumor with annual incidence of 2-3.5/100 000 in population. The histogenesis of salivary gland pleomorphic adenoma is still unclear. One concept sustains the existence of an epithelial-mesenchymal transitions (EMT) process in pleomorphic adenomas by which neoplastic epithelial cells transdifferentiate into mesenchymal cells and leading to tissue heterogeneity from this salivary gland neoplasia. Here we investigate by immunohistochemistry the expression of growth differentiation factor 5 (GDF5) and aggrecan in 15 cases of salivary gland pleomorphic adenomas. We found that both markers were present in normal salivary gland, mainly in the cells that line striated and intercalated ducts suggesting their involvement in the morphogenesis of this duct system. A constant positive reactivity for both markers was recorded in transition regions from tubular proliferative units to myxoid areas suggesting the involvement of an EMT process during the tumorigenesis of such salivary gland neoplasia. Also, both markers may be implicated in the transdifferentiation of neoplastic myoepithelial cells from the myxoid zones to lacuna cells of adjacent chondroid areas completing the morphology of this salivary gland tumor.