Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy-An Observational Study.

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.

Breast carcinoma grading on core needle biopsy - to grade or not to grade?

Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease and the basis for the treatment planning. The concordance rate between CNB and surgical excision specimen in determination of histological grade (HG) varies widely across literature, ranging from 59-91%. The aim of our study was to investigate the level of concordance between CNB and surgical excision specimen for the determination of HG for breast cancer patients. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. The concordance level between core needle biopsy and surgical resection specimen for overall histologic grading was 73%: for tubule formation - 71%, for nuclear pleomorphism - 91%, for the mitotic index - 59%. Our study shows that our institution's histologic grading of CNBs and surgical excisions shows a fairly good correlation and is useful for the planning of treatment.

Dendritic Cell Subpopulations Are Associated with Morphological Features of Breast Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area.

Neoductgenesis in Ductal Carcinoma In Situ Coexists with Morphological Abnormalities Characteristic for More Aggressive Tumor Biology.

Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that is generally indolent, however, could advance to invasive carcinoma in more than one-third of cases if left untreated. Thus, there is continuous research to find DCIS characteristics that would enable clinicians to decide if it could be left without intensive treatment. Neoductgenesis (i.e., formation of the new duct of improper morphology) is a promising, but still not sufficiently evaluated indicator of future tumor invasiveness. We gathered data from 96 cases of DCIS (histopathological, clinical, and radiological) to assess the relationship between the neoductgenesis and well-established features of high-risk tumor behavior. Furthermore, our intention was to determine which degree of neoductgenesis should be considered clinically significant. Our major finding was that neoductgenesis is strictly related to other characteristics that indicate the invasive potential of the tumor and, to achieve more accurate prediction, neoductgenesis should be accordingly recognized to less strict criteria. Therefore, we conclude that neoductgenesis is another important revelator of tumor malignancy and that it requires further investigation during prospective controlled trials.

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden.

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.