Nationwide Real-World Data of Microsatellite Instability and/or Mismatch Repair Deficiency in Cancer: Prevalence and Testing Patterns.

Determination of microsatellite instability (MSI)/mismatch repair (MMR) status in cancer has several clinical implications. Our aim was to integrate MSI/MMR status from patients tested in Greece to assess the prevalence of MSI-high (MSI-H)/deficient MMR (dMMR) per tumor type, testing patterns over time and concordance between MSI and MMR status. We retrospectively recorded MSI/MMR testing data of patients with diverse tumor types performed in pathology and molecular diagnostics laboratories across Greece.

Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy.

Soleus Muscle Single Metastasis from Hepatocellular Carcinoma.

Extrahepatic metastases of hepatocellular carcinoma (HCC) are associated with poor prognosis, while such lesions in skeletal muscles are extremely rare. A unique case of skeletal metastasis in the soleus muscle in a 76-year-old male patient with HCC is reported. The patient presented with a painful palpable mass in his left calf.

Clinical Significance of Major Angiogenesis-Related Effectors in Patients with Metastatic Breast Cancer Treated with Trastuzumab-Based Regimens.

Purpose: Angiogenesis is a crucial phenomenon in the development and progression of breast cancer (BC), but the clinical significance of angiogenesis-related proteins in metastatic BC remains unknown. This study investigates the prognostic value of vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2, VEGFR3) as well as vascular endothelial growth factors A and C (VEGFA and VEGFC) in metastatic BC patients treated with trastuzumab-based regimens.

Materials And Methods: Two hundred female patients were included.

Epigenetic Alterations in Triple-Negative Breast Cancer-The Critical Role of Extracellular Matrix.

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer characterized by genomic complexity and therapeutic options limited to only standard chemotherapy. Although it has been suggested that stratifying TNBC patients by pathway-specific molecular alterations may predict benefit from specific therapeutic agents, application in routine clinical practice has not yet been established. There is a growing body of the literature supporting that epigenetic modifications comprised by DNA methylation, chromatin remodeling and non-coding RNAs play a fundamental role in TNBC pathogenesis.

Correlation between insulin-like peptide 3 and appendix testis length in congenital cryptorchidism.

Aim: The appendix testis (AT) is a vestigial remnant of Müller's paramesonephric duct. Insulin-like 3 hormone (INSL3) is produced in the Leydig cells of the testis. We investigated the possible correlation between AT length and plasma INSL3 concentrations in patients with congenital cryptorchidism (CCO) and patients with hydrocele, who served as controls.

Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?

Background: Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group.

Methods: We examined 1011 patients (median follow-up 130.

PD-L1 Expression and Tumor-infiltrating Lymphocytes in Breast Cancer: Clinicopathological Analysis in Women Younger than 40 Years Old.

Background/aim: To evaluate the association between programmed cell death ligand 1 (PD-L1) expression on both tumor cells (TC) and inflammatory cells (IC), tumor infiltrating lymphocytes (TILs), CD3 and CD8 lymphocytes and other clinicopathological parameters in primary infiltrative breast cancer (IBC) of young women, a population shown to have a worse prognosis.

Materials And Methods: A retrospective study was performed collecting data from patients younger than 40 years old. Forty-five young women with IBC were included.

Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab.

Background: Alternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms.

Patients And Methods: Formalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected.

Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer.

Background/aim: Early-stage colorectal cancer (CRC) carries a wide range of survival probabilities. Novel biomarkers in this setting are eagerly awaited. Cancer stem cells (CSCs) are considered one of the reasons for treatment failure.

Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming.

Objective: Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis.

Design: DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues.

Osteolytic lesions (brown tumors) of primary hyperparathyroidism misdiagnosed as multifocal giant cell tumor of the distal ulna and radius: a case report.

Background: Brown tumors represent a rare clinical manifestation reported in approximately 3% of patients with primary hyperparathyroidism and correspond to radiologically osteolytic lesions with well-defined borders in different parts of the skeleton.

Case Presentation: We report the case of a 53-year-old white man who presented to our hospital with osteolytic lesions of his distal ulna and radius, causing pain and swelling of 2-month duration. A subsequent biopsy revealed histological features consistent with giant cell tumor and a complete resection of his distal ulna was followed, along with curettage and cementoplasty of the distal radial metaphysis.

Towards tumor immunodiagnostics.

Immunodiagnostic markers applicable on tissue or cytologic material may be prognostic or predictive of response to immunomodulatory drugs and may also be classified according to whether they are cell-specific or tumor-tissue-specific. Cell-specific markers are evaluated under the microscope as (I) morphological, corresponding to the assessment of tumor infiltrating immune cells on routine hematoxylin & eosin (H&E) sections; and (II) immunophenotypic, including the immunohistochemical (IHC) assessment of markers characteristic for tumor infiltrating immune cells. Tumor-tissue-specific markers are assessed in tissue extracts that may be enriched in neoplastic cells but almost inevitably also contain stromal and immune cells infiltrating the tumor.

A chemical energy approach of avascular tumor growth: multiscale modeling and qualitative results.

In the present manuscript we propose a lattice free multiscale model for avascular tumor growth that takes into account the biochemical environment, mitosis, necrosis, cellular signaling and cellular mechanics. This model extends analogous approaches by assuming a function that incorporates the biochemical energy level of the tumor cells and a mechanism that simulates the behavior of cancer stem cells. Numerical simulations of the model are used to investigate the morphology of the tumor at the avascular phase.

Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials.

Background: Tumor infiltrating lymphocytes (TILs) are considered in the prognosis of breast cancer (BC) patients. Here, we investigated the prognostic/predictive effect of TILs in patients treated in the frame of four prospective trials with adjuvant anthracycline-based chemotherapy in the pre- and post-trastuzumab era.

Methods: TILs density was histologically assessed as percentage of stromal area on whole routine sections of 2613 BC (1563 Luminal A/B; 477 Luminal HER2; 246 HER2-enriched; 327 triple negative [TNBC]) and were evaluated as high/low at three cut-offs (c/o; 50% [lymphocytic predominance, LP], 35% and 25%), in separate training and validation sets.

Gangrenous Cholecystitis Related to Transcatheter Arterial Chemoembolization (TACE) Treatment for Hepatocellular Carcinoma.

A 69-year-old male with a history of hepatitis B-induced cirrhosis underwent segmental liver resection for hepatocellular carcinoma. At his 12-month follow-up, local recurrence in segment VII was diagnosed, measuring 7.8 by 6.

Expression of phosphorylated Akt, mTOR and MAPK in type I endometrial carcinoma: clinical significance.

Background/aim: The Akt/mTOR and MAPK pathways are frequently activated in various tumor types but data on endometrial carcinoma are limited. The aim of the present study was to investigate the clinical significance of the expression of phosphorylated MAPK, Akt and mTOR (p-MAPK, p-Akt, p-mTOR) in type I endometrial carcinoma.

Materials And Methods: The study comprised of 103 formalin-fixed paraffin-embedded (FFPE) type I endometrial carcino ma cases, retrospectively retrieved and assessed by immuno histochemistry for p-MAPK, p-Akt and p-mTOR expression.

Impact of tumor angiogenic profile on the outcome of patients with metastatic breast carcinoma treated with weekly docetaxel. A Hellenic Cooperative Oncology Group (HeCOG) study.

Background: Metronomic taxane administration has putative antiangiogenic properties. Herein, we examined the baseline tumor angiogenic profile of patients with metastatic breast carcinoma (MBC) in a prospective-retrospective translational research study. The interplay between the angiogenic factors expressed in the tumors and their prognostic value in MBC were investigated.

Targeted pathways in breast cancer: molecular and protein markers guiding therapeutic decisions.

Breast carcinoma is currently considered as a group of diseases, differing not only in histopathologic phenotype, as indicated by histologic type and grade, but also in their protein, genetic and epigenetic molecular profile. The standard of care indicates that the core information for patient management includes data on Estrogen Receptor (ER), Progesterone Receptor (PgR) and Human Epidermal Growth Factor Receptor 2 (HER2), while there is an emerging role for the proliferation marker Ki67. These indices can be provided even in low resource settings and are indispensable for prognostication and therapeutic patient management.

Estrogen receptor β2 is inversely correlated with Ki-67 in hyperplastic and noninvasive neoplastic breast lesions.

Purpose: The purpose of the study is to compare expression levels of ΕRα, ERβ1, ERβ2 and cell proliferation marker Ki-67 in normal breast and hyperplastic and noninvasive neoplastic breast lesions.

Materials And Methods: Routinely processed breast tissue from 55 patients provided 65 cases of noninvasive lesions, namely, epithelial hyperplasia of usual type (HUT), apocrine metaplasia (AM), atypical hyperplasia (AH) and ductal carcinoma in situ (DCIS) and 14 cases of adjacent normal breast tissue. Expression of ERα, ERβ1 and ERβ2 were evaluated using immunohistochemistry and correlated with Ki-67 labeling index (Ki-67 LI) and menopausal status of the patients.

The prognostic role of preoperative serum CA 125 levels in patients with endometrial carcinoma.

Purpose: Previous studies have shown that elevated preoperative serum CA 125 levels strongly correlate with various clinical and pathological variables and prognosis of patients with endometrial carcinoma (EC). The aim of the present study was to evaluate the clinical significance of preoperative serum CA 125 levels in patients with EC.

Methods: A retrospective study of all EC patients treated at our institution between 1995 and 2010 with available follow-up was conducted.