BRACS: A Dataset for BReAst Carcinoma Subtyping in H&E Histology Images.

Breast cancer is the most commonly diagnosed cancer and registers the highest number of deaths for women. Advances in diagnostic activities combined with large-scale screening policies have significantly lowered the mortality rates for breast cancer patients. However, the manual inspection of tissue slides by pathologists is cumbersome, time-consuming and is subject to significant inter- and intra-observer variability.

NTRK Gene Fusion Detection in Atypical Spitz Tumors.

Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined.

Hierarchical graph representations in digital pathology.

Cancer diagnosis, prognosis, and therapy response predictions from tissue specimens highly depend on the phenotype and topological distribution of constituting histological entities. Thus, adequate tissue representations for encoding histological entities is imperative for computer aided cancer patient care. To this end, several approaches have leveraged cell-graphs, capturing the cell-microenvironment, to depict the tissue.

The Ratio of GrzB - FoxP3 over CD3 T Cells as a Potential Predictor of Response to Nivolumab in Patients with Metastatic Melanoma.

The understanding of the molecular pathways involved in the dynamic modulation of the tumor microenvironment (TME) has led to the development of innovative treatments for advanced melanoma, including immune checkpoint blockade therapies. These approaches have revolutionized the treatment of melanoma, but are not effective in all patients, resulting in responder and non-responder populations. Physical interactions among immune cells, tumor cells and all the other components of the TME (i.

Peritumoral Immune Infiltrate as a Prognostic Biomarker in Thin Melanoma.

Thin melanomas are tumors less than 1 mm thick according to Breslow classification. Their prognosis is in most cases excellent. However, a small subset of these tumors relapses.

Morphological and pathological features of basal-like breast cancer.

Basal-like breast cancer (BLBC) is characterized by high grade, high mitotic indices, presence of central necrotic or fibrotic zones, and lymphocytic infiltrate. Patients presenting with BLBC have a poor prognosis and a short-term disease-free and overall survival. BLBCs may include different histological types of breast cancers but the most common histological type is represented by invasive ductal carcinomas of no special type (IDC-NST).

The effects of the use of platelet-rich plasma gel on local recurrence in an animal model of human fibrosarcoma.

Background: Platelet-rich-plasma (PRP) is largely used, thanks to its properties, as wound therapy after surgical resection. Several studies and clinical findings have demonstrated that the PRP can accelerate the regeneration and the repair of tissues through the action of the platelet-derived growth factors.

Material And Methods: Our study aimed to investigate the effects of PRP-gel on the rate of tumor relapse by using a mouse model of Human Fibrosarcoma (HF).

CXCL12 loaded-dermal filler captures CXCR4 expressing melanoma circulating tumor cells.

Development of distant metastasis relies on interactions between cancer and stromal cells. CXCL12, also known as stromal-derived factor 1α (SDF-1α), is a major chemokine constitutively secreted in bone marrow, lymph nodes, liver and lung, playing a critical role in the migration and seeding of neoplastic cells. CXCL12 activates the CXCR4 receptor that is overexpressed in several human cancer cells.

Mutated Von Hippel-Lindau-renal cell carcinoma (RCC) promotes patients specific natural killer (NK) cytotoxicity.

Background: Previous evidence demonstrated that restoration of wild type VHL in human renal cancer cells decreased in vitro NK susceptibility. To investigate on the role of tumoral VHL status versus NK capability in renal cancer patients, 51 RCC patients were characterized for VHL mutational status and NK function.

Methods: VHL mutational status was determined by direct DNA sequencing on tumor tissue.

Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma.

Background: Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years.

COX-2 expression positively correlates with PD-L1 expression in human melanoma cells.

Background: The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma.

Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival.

The possible correlation between cyclooxygenase-2 (COX-2) expression and disease progression in melanoma is still a matter of debate. Analysis of COX-2 expression in 45 lymph node melanoma metastases demonstrates a significant correlation between the percent of expression and progression free survival (PFS). A positive COX-2 expression ≥10% (COX-2high), as opposite to a positive expression ≤9% (COX-2low), translated into a striking significant reduction of PFS of about 3 years.

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types.

In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined.

Antitumor Activity of BRAF Inhibitor and IFNα Combination in BRAF-Mutant Melanoma.

Background: BRAF(V600E)-mediated MAPK pathway activation is associated in melanoma cells with IFNAR1 downregulation. IFNAR1 regulates melanoma cell sensitivity to IFNα, a cytokine used for the adjuvant treatment of melanoma. These findings and the limited therapeutic efficacy of BRAF-I prompted us to examine whether the efficacy of IFNα therapy of BRAF(V600E) melanoma can be increased by its combination with BRAF-I.

LncRNA HOTAIR as Prognostic Circulating Marker and Potential Therapeutic Target in Patients with Tumor Diseases.

In the recent years the importance of the role played by non-coding RNA on the regulation of gene expression was increased by numerous studies. The research mainly focused on small ncRNAs, such as miRNAs, while the functions of long non-coding RNA (lncRNA) have been much less studied. lncRNAs can be transcribed from intergenic, intragenic or specific chromosomal regions.

Immune-phenotypical markers for the differential diagnosis of melanocytic lesions.

For specific subsets of melanocytic proliferations, there are morphologic limitations in the histological diagnosis, especially for borderline melanocytic tumors. In particular, Spitzoid proliferations can be difficult to diagnose. For these reasons, in the last years, clinic research has focused attention on discovery of new diagnostic markers.

Clinicopathologic features and surgical management of primary umbilical melanoma: a case series.

Background: Primary umbilical melanoma is an uncommon tumor that is poorly described in the medical literature. The umbilical region is a particular anatomic site owing to the presence of embryonal remnants, which can be a potential metastatic pathway, as well as the braided lymphatic network drainage. Hence, primary malignant neoplasms affecting the umbilicus require a different and more radical surgical approach compared with other melanomas.

Ran signaling in melanoma: implications for the development of alternative therapeutic strategies.

We performed a comparative study between two human metastatic melanoma cell lines (A375 and 526), and melanocytes (FOM78) by gene expression profiling and pathway analysis, using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) software. Genes involved in Ran signaling were significantly over-represented (p ≤ 0.001) and up-regulated in melanoma cells.

SPARC/osteonectin is involved in metastatic process to the lung during melanoma progression.

The existence of a "metastasis gene signature" that predisposes primary breast cancer cells to metastasize to the lungs has been recently highlighted by gene expression profiling studies. The combination of genes responsible for this process includes genes encoding several metalloproteinases as well as the gene encoding SPARC (secreted protein acidic and rich in cysteine)/osteonectin. SPARC is involved in normal tissue remodeling as it regulates the deposition of extracellular matrix, but also plays a role in neoplastic transformation.

CD90 expression in atypical meningiomas and meningioma metastasis.

Objectives: Meningiomas are slow-growing intracranial/intraspinal tumors, with a wide range of histopathologic variants. The more aggressive atypical and malignant types can disseminate via the venous system, lymphatic, system, or cerebrospinal fluid, with the lung and pleura being the most common sites of extracranial metastases. A case of metastatic meningioma with high expression of CD90 was spotted during a review of flow cytometry data for lung malignancies.

Surgical management of sentinel lymph node biopsy outside major nodal basin in patients with cutaneous melanoma.

Purpose: To assess the incidence of nonmajor lymphatic basin sentinel nodes in patients with cutaneous melanoma in order to propose a correct nomenclature and inform appropriate surgical management.

Methods: This was a retrospective review of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site. Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic basin along the lymphatic drainage to a major classical nodal basin) or interval (located anywhere along the lymphatics between the primary tumor site and the nearest lymphatic basin) sentinel nodes.

Microenvironment and tumor progression of melanoma: new therapeutic prospectives.

Malignant melanoma is a very representative disease in terms of tumor progression processes. During its evolution, a series of events takes place; among these, the cells' 'out-of-control' growth and loss of homeostasis play crucial roles in the genesis of the tumor itself and its subsequent progression. These events involve several molecular mechanisms associated with both melanocyte transformation and changes to/in the surrounding microenvironment.