Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples. Positive cells were counted within the tumor bed and at the invasive margin. For all analyzed MC subpopulations, we observed statistically significant differences between individual molecular subtypes of breast cancer. The significantly higher numbers of intratumoral chymase- and tryptase-positive mast cells were observed in luminal A and luminal B tumors compared to triple-negative and HER2+ non-luminal lesions. A denser MC infiltration was associated with lower tumor grade, higher ER and PR expression, lower proliferation rate as well as the lack of HER2 overexpression. The results obtained in our study indicate a possible association of chymase- and tryptase-positive MCs with more favorable cancer immunophenotype and with beneficial prognostic indicators in breast cancer.

T lymphocytes are the most numerous immune cells in tumor-associated infiltrates and include several subpopulations of either anticancer or pro-tumorigenic functions. However, the associations between levels of different T cell subsets and breast cancer molecular subtypes as well as other prognostic factors have not been fully established yet. We performed immunohistochemistry for CD8 (cytotoxic T cells (CTL)), FOXP3 (regulatory T cells (Tregs)), and GATA3 (Th2 cells) in 106 formalin-fixed paraffin-embedded invasive breast cancer tissue samples and analyzed both the numbers and percentages of investigated cells in tumor-associated infiltrates. We observed that triple-negative breast cancer (TNBC) and HER2+ non-luminal breast tumors were associated with more numerous CTLs and Tregs and a higher Treg/Th2 cell ratio as compared with luminal A subtype. A higher Treg percentage was related to a decreased hormone receptor expression, an increase in the Ki67 level, a greater tumor size of luminal tumors, and the presence of lymph node metastases. Moreover, differences in the composition of T cell infiltrates were associated with HER2 status and histologic grade and type, and a distinct immune pattern was observed in tumors of different phenotypes regarding pT stage and nodal status. The results of our work show the diversity of T cell infiltrates in primary invasive breast cancers of different phenotypes and suggest that progression of luminal or non-luminal tumors is related to distinct tumor-associated T cell composition.

BackgroundMutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland.MethodsWe examined the entire coding sequences of the BRCA1 and BRCA2 genes and genotyped a recurrent mutation of the PALB2 gene (c.509_510delGA) in 121 women with familial and/or early-onset breast or ovarian cancer from Southern Poland.ResultsA BRCA1 mutation was identified in 11 of 121 patients (9.1 %) and a BRCA2 mutation was identified in 10 of 121 patients (8.3 %). Two founder mutations of BRCA1 accounted for 91 % of all BRCA1 mutation carriers (c.5266dupC was identified in six patients and c.181 T > G was identified in four patients). Three of the seven different BRCA2 mutations were detected in two patients each (c.9371A > T, c.9403delC and c.1310_1313delAAGA). Three mutations have not been previously reported in the Polish population (BRCA1 c.3531delT, BRCA2 c.1310_1313delAAGA and BRCA2 c.9027delT). The recurrent PALB2 mutation c.509_510delGA was identified in two patients (1.7 %).ConclusionsThe standard panel of BRCA1 founder mutations is sufficiently sensitive for the identification of BRCA1 mutation carriers in Southern Poland. The BRCA2 mutations c.9371A > T and c.9403delC as well as the PALB2 mutation c.509_510delGA should be included in the testing panel for this population.

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Dendritic cells (DCs) constitute a part of the tumour microenvironment, but we are still far from understanding their complex role in immune response to the tumour. This study aimed to investigate the density of DCs expressing CD1a, CD83, CD123, DC-LAMP3 (CD208) and DC-SIGN (CD209) in breast cancer. The correlations between DC density and molecular subtype of breast cancer, its hormone receptor status, spatial location and their associations with clinical and pathological prognostic factors were evaluated. We have shown that intratumoural CD1a+ cells were significantly associated with progression-free survival. For LAMP3+ and CD123+ DCs, higher cell densities were associated with non-luminal as compared to luminal cancer phenotype. In contrast, dense CD83+ DC infiltrate was observed in luminal tumours. The number of CD1a+ DCs in both locations was the highest in luminal B/HER2+ cancers. The highest positive cell count of LAMP3+ cells was observed in the triple-negative subtype in both locations. We found higher numbers of LAMP3+ DCs both intratumourally and at the invasive margin, as well as CD123+ DCs intratumourally in tumours with negative expression of oestrogen or progesterone receptors. Our study demonstrates associations between DC subpopulations and histological and clinical characteristics, as well as molecular subtypes in breast carcinoma.