Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?

In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal growth factor receptor 2), and CK5 (cytokeratin 5) status and the proliferation marker Ki-67 were determined by immunohistochemistry on specimens from 43 women. All selected cases were diagnosed as invasive breast carcinomas, of no special type (NST), G2 grade of differentiation. The most frequently encountered subtype at both sites was luminal B. We determined that tumor profile evaluated by surrogate markers is not stable during the metastatic process. The total rate of shifted cases was 23.26% (10 cases), and the highest rate of shifting (6.98%) was encountered from luminal B/Ki-67 to luminal A subtype. In five cases, the subtype shifted to a poorer one according to prognosis. These data support the hypothesis that breast cancer is a heterogeneous disease, with substantial variability of cellular components within each category, a statement applicable to invasive breast carcinomas of NST type too. The receptor profile of this carcinoma, indicated by surrogate markers, is not stable throughout the metastatic process.

Mast cells stimulate lymphangiogenesis in the gingiva of patients with periodontal disease.

The presence and distribution of lymphatic vessels and mast cells in the gingiva under normal and pathological conditions have been reported by several studies, but the relationship between them during inflammatory lymphangiogenesis is virtually unknown. The aim of the present study was to investigate the lymphatic microvessel density (LMVD) and mast cell density (MCD) in the gingiva of patients with periodontal disease compared to normal-like gingiva. Gingival punch biopsies from 51 patients with periodontal disease were investigated. MCs and LVs were detected by double-immunohistochemistry, using primary antibodies against mast cell tryptase and D2-40. The inflammatory infiltrate was evaluated on a scale from 0 (absent) to +3 (severe inflammation). MCs and LVs were counted in the same microscopic field for each case at ×200 magnification. We found a significant increase in the number of both MCs and LVs in cases with mild and moderate inflammatory changes, followed by a slight decrease in cases with severe inflammation. We have shown a particular association between MCs and LVs that may support the contribution of MCs to the development of the lymphatic vasculature in inflammatory conditions. MCD correlated with LMVD in all cases with mild and moderate inflammatory changes, but not in cases with severe inflammation. No correlation was found between MCD/LMVD and the density of the inflammatory infiltrate. Our results suggest the potential involvement of MCs in the induction and maintenance of lymphangiogenesis in the gingiva of patients with periodontal disease in the early steps of evolution.

Differential expression of e-cadherin in primary breast cancer and corresponding lymph node metastases.

BACKGROUND/AIM: E-Cadherin is a marker with a controversial function. Its role is often interpreted in the context of the epithelial-mesenchymal transition. In ambiguous cases, it is used as a phenotypic marker of lobular subtype of breast carcinoma. It has been well-studied in primary cancer, but its expression after metastasis is not well-described. The aim of this study was to determine the evolution of E-cadherin expression in no special type (NST) primary breast carcinoma and to correlate this with that in distant, paired nodal metastases (LNM) and molecular classification. MATERIAL AND METHODS: We processed 88 invasive breast carcinomas of NST type and their paired LNM. The specimens were formalin-fixed and paraffin embedded. Sections were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), basal cytokeratin CK5, nuclear protein Ki67 and E-cadherin with a Leica Bond-Max autostainer. RESULTS: The results obtained were grouped into four molecular subtypes: Luminal A, luminal B, HER2-overexpressing, and triple-negative/basal-like. We found that the frequency of E-cadherin expression was higher (95.45%) in primary sites than in LNM (72.73%). E-Cadherin from primary breast cancer correlated positively only with E-cadherin in LNM (p≤0.003). A single positive correlation of E-cadherin with ER (p≤0.007) LNM was found. CONCLUSION: E-Cadherin expression is not stable during the metastatic process. Its expression in LNM is lower than in primary sites. E-Cadherin expression in primary sites positively correlates with E-cadherin from LNM.

Tryptase-positive and CD117 Positive Mast Cells Correlate with Survival in Patients with Liver Metastasis.

The prognostic value of mast cells (MCs) in patients with liver metastases is a relatively new topic. The present study comparatively assessed tryptase-positive (MCT(+)) and CD117(+) MCs in liver metastases from various sites and correlated their expression with clinicopathological prognostic factors and survival. Our data pointed to differences in MCT and CD117 expression in liver metastases that seem to be related to the origin of the primary tumor. For colon cancer metastases, intra-tumor MCT(+) MCs were significantly correlated with tumor grade and nodal status, while peritumoral MCT(+) MCs and peritumoral CD117(+) MCs were significantly correlated with overall survival. No significant correlations between MCT(+) and CD117(+) MC number and clinicopathological parameters or survival were found for gastric cancer metastases. To the best of our knowledge, this is the first report regarding MC involvement in liver metastases from different malignant tumors correlated with clinicopathological parameters and overall survival. Different mast cell phenotype together with their specific correlation with tumor grade, nodal status and survival suggest their involvement in the metastatic process in a specific manner related to tumor origin. Mast cells from liver metastases remain a questionable issue regarding their origin, pathogenic role and their ability to be potential targets for adjuvant therapy.