Invasive micropapillary carcinoma of the breast and invasive breast carcinoma of no special type: a comparison of claudin proteins' expression and its impact on survival.

Invasive micropapillary carcinoma of the breast is characterized by clusters of cells presenting with inverted polarity. Although the apico-basal polarity is a fundamental property of the epithelium, the biological alterations leading to the inside-out pattern observed in invasive micropapillary carcinoma (IMPC) remain mostly unknown. The regulation of tight junctions in polarity formation and maintenance is acknowledged.

Vicious Circle With Venous Hypertension, Irregular Flow, Pathological Venous Wall Remodeling, and Valve Destruction in Chronic Venous Disease: A Review.

Substantial advances occurred in phlebological practice in the last two decades. With the use of modern diagnostic equipment, the patients' venous hemodynamics can be examined in detail in everyday practice. Application of venous segments for arterial bypasses motivated studies on the effect of hemodynamic load on the venous wall.

Research autopsy programmes in oncology: shared experience from 14 centres across the world.

While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research.

Association of Baseline Tumor-Specific Neoantigens and CD8 T-Cell Infiltration With Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors.

Purpose: Recent evidence has shown that higher tumor mutational burden strongly correlates with an increased risk of immune-related adverse events (irAEs). By using an integrated multiomics approach, we further studied the association between relevant tumor immune microenvironment (TIME) features and irAEs.

Methods: Leveraging the US Food and Drug Administration Adverse Event Reporting System, we extracted cases of suspected irAEs to calculate the reporting odds ratios (RORs) of irAEs for cancers treated with immune checkpoint inhibitors (ICIs).

Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.

Alterations in mTOR signalling molecules, including RICTOR amplification, have been previously described in many cancers, particularly associated with poor prognosis. In this study, RICTOR copy number variation (CNV) results of diagnostic next-generation sequencing (NGS) were analysed in 420 various human malignant tissues. RICTOR amplification was tested by Droplet Digital PCR (ddPCR) and validated using the "gold standard" fluorescence in situ hybridisation (FISH).

The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience.

Background: Breast cancer has been categorized into molecular subtypes using immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH) since the early 2000s. However, recent research suggests that gene expression testing, specifically Prosigna Prediction Analysis of Microarray 50 (PAM50), provides more accurate classification methods. In this retrospective study, we compared the results of IHC/FISH and PAM50 testing.

Strong desmin immunoreactivity in the myocardial sleeves around pulmonary veins, superior caval vein and coronary sinus supports the presumed arrhythmogenicity of these regions.

Myocardial sleeve around human pulmonary veins plays a critical role in the pathomechanism of atrial fibrillation. Besides the well-known arrhythmogenicity of these veins, there is evidence that myocardial extensions into caval veins and coronary sinus may exhibit similar features. However, studies investigating histologic properties of these structures are limited.

Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis.

Organic anion transporting polypeptide 3A1 (OATP3A1, encoded by the gene) is a prostaglandin, oligopeptide, and steroid/thyroid hormone transporter with wide tissue distribution, expressed, e.g., in the human brain and testis.

The Prognostic Relevance of PMCA4 Expression in Melanoma: Gender Specificity and Implications for Immune Checkpoint Inhibition.

PMCA4 is a critical regulator of Ca homeostasis in mammalian cells. While its biological and prognostic relevance in several cancer types has already been demonstrated, only preclinical investigations suggested a metastasis suppressor function in melanoma. Therefore, we studied the expression pattern of PMCA4 in human skin, nevus, as well as in primary and metastatic melanoma using immunohistochemistry.

Accurate Quantitative Histomorphometric-Mathematical Image Analysis Methodology of Rodent Testicular Tissue and Its Possible Future Research Perspectives in Andrology and Reproductive Medicine.

Infertility is increasing worldwide; male factors can be identified in nearly half of all infertile couples. Histopathologic evaluation of testicular tissue can provide valuable information about infertility; however, several different evaluation methods and semi-quantitative score systems exist. Our goal was to describe a new, accurate and easy-to-use quantitative computer-based histomorphometric-mathematical image analysis methodology for the analysis of testicular tissue.

Cell polarity and cell adhesion associated gene expression differences between invasive micropapillary and no special type breast carcinomas and their prognostic significance.

Invasive micropapillary carcinoma of the breast (IMPC) has been in the focus of several studies given its specific histology and clinicopathological course. We analysed mRNA expression profiles and the prognostic value of 43 genes involved in cell polarity, cell-adhesion and epithelial-mesenchymal transition (EMT) in IMPC tumors and compared them to invasive breast carcinomas of no special type (IBC-NST). IMPCs (36 cases), IBC-NSTs (36 cases) and mixed IMPC-IBC NSTs (8 cases) were investigated.

Initiation of reticular and spider veins, incompetent perforantes and varicose veins in the saphenous vein network of the rat.

In an attempt to induce experimental varicosity, reverse perforant vein development was initiated in the rat leg by applying a chronic (14 and 32 weeks) partial stricture on the main branch of the deep femoral vein. At surfacing of the incompetent perforantes, typical reticular vein plaques and spider veins were identified by video-microscopy and quantitative histology. Deep vein blood was channeled by them into the saphenous vein system, the extra flow deforming these vessels, causing local dilations and broken course, even undulations of larger branches.

In Situ Metabolic Characterisation of Breast Cancer and Its Potential Impact on Therapy.

In spite of tremendous developments in breast cancer treatment, the relatively high incidence of relapsing cases indicates a great need to find new therapeutic strategies in recurrent, metastatic and advanced cases. The bioenergetic needs of growing tumours at the primary site or in metastases-accumulating genomic alterations and further heterogeneity-are supported by metabolic rewiring, an important hallmark of cancer. Adaptation mechanisms as well as altered anabolic and catabolic processes balance according to available nutrients, energy, oxygen demand and overgrowth or therapeutic resistance.

Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer.

We aimed to analyze the expression of cell-cycle regulation markers - minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) - in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival.

Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer.

Chemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes. It is not known, however, whether treatment with various chemotherapeutic agents with different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in residual cancer.

Dynamic FDG-PET/CT in the Initial Staging of Primary Breast Cancer: Clinicopathological Correlations.

Our aim was to evaluate correlation between clinicopathological features (clinical T and clinical N stages; histological type; nuclear grade; hormone-receptor and HER2 status, proliferation activity and tumor subtypes) of breast cancer and kinetic parameters measured by staging dynamic FDG-PET/CT examinations. Following ethical approval and patients' informed consent we included 34 patients with 35 primary breast cancers in our prospective study. We performed dynamic PET imaging, and assessed plasma activity noninvasively.

LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas.

Purpose: To determine the associations between lysosomal-associated transmembrane protein 4b (LAPTM4B) gene copy number and response to different chemotherapy regimens in hormone receptor negative (HR-) primary breast carcinomas.

Patients And Methods: Two cohorts were analyzed: (1) 69 core biopsies from HR-breast carcinomas treated with neoadjuvant chemotherapy (anthracycline based in 72.5% of patients and non-anthracycline based in 27.

Presence of cardiomyocytes exhibiting Purkinje-type morphology and prominent connexin45 immunoreactivity in the myocardial sleeves of cardiac veins.

Background: Pulmonary vein (PV) myocardium is a known source of atrial fibrillation. A debated question is whether myocardial extensions into caval veins and coronary sinus (CS) have similar properties. No studies have documented specific pacemaker and/or conducting properties of human extracardiac myocardium.

PD-1, PD-L1 and CTLA-4 in pregnancy-related - and in early-onset breast cancer: A comparative study.

Purpose: We aimed to compare the immunohistochemical expression of PD-1, PD-L1 and CTLA-4 of pregnancy-related breast cancer (PRBC) and early onset non-PRBC (YWBC), and their prognosis prediction potential was correlated to that of conventional clinicopathological factors.

Methods: Twenty-one PRBC cases were paired with 21 YWBC in this matched case-control study. Immune-checkpoint markers (ICM) were evaluated with immunohistochemistry (IHC) on whole slides using the following antibodies: PD-1 (NAT-105), PD-L1 (28-8) and CTLA-4 (F-8).

Erratum: Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations.

This corrects the article DOI: 10.1038/ncomms14944.

Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations.

Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression.

Reproducibility and Prognostic Potential of Ki-67 Proliferation Index when Comparing Digital-Image Analysis with Standard Semi-Quantitative Evaluation in Breast Cancer.

In this study, the reproducibility of Ki-67 proliferation index (KIPI) was investigated by comparing the semi-quantitative (SQ) results of three assessors with those of digital image-analysis (DIA) methods. The prognostic significance of the two approaches was also correlated with clinical outcome. Tissue microarrays of duplicate 2 mm cores were constructed from representative areas of formalin-fixed and paraffin-embedded tumor blocks of 347 breast cancer patients.

Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy.

Background: Studies have partly demonstrated the clinical validity of Ki-67 as a predictive marker in the neoadjuvant setting, but the question of the best cut-off points as well as the importance of this marker as a prognostic factor in partial responder/non-responder groups remains uncertain.

Methods: One hundred twenty patients diagnosed with invasive breast cancer and treated with neoadjuvant chemotherapy (NAC) between 2002 and 2013 were retrospectively recruited to this study. The optimal cut-off value for Ki-67 labeling index (LI) to discriminate response to treatment was assessed by receiver operating characteristic (ROC) curve analysis.

Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer: does the antibody matter?

Although several antibodies are available for immunohistochemical detection of Ki-67, even the most commonly used MIB-1 has not been validated yet. Our aim was to compare 5 commercially available antibodies for detection of Ki-67 in terms of agreement and their ability in predicting prognosis of breast cancer. Tissue microarrays were constructed from 378 breast cancer patients' representative formalin-fixed, paraffin-embedded tumor blocks.