Prognostic value and multifaceted roles of tetraspanin CD9 in cancer.

CD9 is a crucial regulator of cell adhesion in the immune system and plays important physiological roles in hematopoiesis, blood coagulation or viral and bacterial infections. It is involved in the transendothelial migration of leukocytes which might also be hijacked by cancer cells during their invasion and metastasis. CD9 is found at the cell surface and the membrane of exosomes affecting cancer progression and therapy resistance. High expression of CD9 is mostly associated with good patients outcome, with a few exceptions. Discordant findings have been reported for breast, ovarian, melanoma, pancreatic and esophageal cancer, which might be related to using different antibodies or inherent cancer heterogeneity. According to in vitro and in vivo studies, tetraspanin CD9 is not clearly associated with either tumor suppression or promotion. Further mechanistic experiments will elucidate the role of CD9 in particular cancer types and specific conditions.

Single-cell protein profiling defines cell populations associated with triple-negative breast cancer aggressiveness.

Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single-cell techniques in combination with next-generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single-cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial-mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor-associated stroma. Furthermore, in a retrospective tissue-microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.

Histiocytic Sarcoma with an Unusual Clinical Manifestation Imitating Malignant Vascular Tumor: A Case Report.

BACKGROUND Histiocytic sarcoma is a rare malignant hematopoietic neoplasm with morphologic and immunohistochemical features of histiocytic differentiation, usually with unfavorable prognosis. Despite aggressive biological behavior, in subgroup of patients with localized disease, the prognosis can be very good. Few publications are available on localized cases of histiocytic sarcoma. These occur infrequently and continue to be a poorly-recognized morphological entity. CASE REPORT A 73-year old man treated for Parkinson syndrome presented with a tumor resistance on the dorsal surface of the left forearm. This lesion was clinically seen as an organized hematoma and was surgically resected. Histologically, the tumor was situated in the dermis and subcutis and it consisted of multiple neoplastic nodules. Vasoformative growth patterns with the vascular-like spaces containing erythrocytes and hemosiderin pigment presence simulated the morphology of angiosarcoma. Based on the immunohistochemical characteristics, we diagnosed the tumor as cutaneous histiocytic sarcoma. Genetic analysis revealed immunoglobulin heavy-chain gene rearrangement without any concomitant hematological malignancy. The patient demonstrated no systemic disease or impairment associated with diagnosed histiocytic sarcoma, and no recurrence has been found to date. CONCLUSIONS We report a case of primary cutaneous histiocytic sarcoma with an excellent outcome after surgical treatment only. Clinical data and histopathological and immunohistochemical evaluation were essential to rule out other malignant tumors in the differential diagnosis. Genetic analysis together with up-to-date knowledge and understanding of principles of tumorous transformations helped to diagnose this poorly-recognized entity with various clinical behaviors.

The changes of angiogenesis and immune regulations in stromal microenvironment of cutaneous melanomas.

Tumour microenvironment contributes to growth and metastasis, where angiogenesis and immune alteration suppressing its effectory function belong to main factors. Our study is focused on an analysis of microvascular density (MVD), quantification of FOXP3+ T regulatory lymphocytes (Tregs) and PD-L1 lymphocytes, which are associated with a tumour-cells immune escape mechanism. We examined 95 cutaneous melanomas devided in four groups according to TNM classification - pT1 (35), pT2 (21), pT3 (21), pT4 (18) and 25 melanocytic nevi as a control group. Investigated parameters were detected on paraffin embedded tissues by indirect immunohistochemistry, and evaluated by light microscope in central (C) and at peripheral regions (P) on a 1mm2 „hot spot“ region (the area of the highest density). We found a significant MVD increase correlating with a stage of disease, mostly at the edge of tumours (p=0,0001). Lymphocytic PD-L1 expresion was increased in melanomas of pT3 and pT4 stages, also predominantly at the periphery of lesions (p=0,0001). Numbers of FOXP3 lymphocytes positively correlated with a melanoma stage, where higher values were observed in central areas (p=0,008). Our study documents that stimulation of angiogenesis and induction of an adaptive immune response correlate with a melanoma stage. The most prominent changes are at the tumour periphery confirming heterogeneity of a tumour stroma, which is more prominent in advanced tumours, and which may contribute to higher agresivity of these stages.