Colorectal Adenocarcinomas Harboring ALK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 12 Cases and Review of the Literature.

This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody.

Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity.

Cytoplasmic HAX1 Is an Independent Risk Factor for Breast Cancer Metastasis.

HAX1 is an antiapoptotic factor involved in the regulation of cell migration and calcium homeostasis, overexpressed in several cancers, including breast cancer. It has been suggested that HAX1 is also implicated in metastasis. Herein we report the results of meta-analysis of expression, based on publicly available data, which confirms its significant overexpression in breast cancer and demonstrates copy number gain and prognostic value of overexpression for metastatic relapse in ER+ tumors.

Primary malignant melanoma of esophagus: clinicopathologic characterization of 20 cases including molecular genetic profiling of 15 tumors.

Primary malignant melanoma of esophagus is very rare, and its clinicopathologic and genetic features have not been extensively investigated. In this study, 20 tumors from 14 male and 6 female patients (40-79 years old) were evaluated. Dysphagia, chest pain, and weight loss were frequent symptoms.

New fusion sarcomas: histopathology and clinical significance of selected entities.

Many sarcomas contain gene fusions that can be pathogenetic mechanisms and diagnostic markers. In this article we review selected fusion sarcomas and techniques for their detection. CIC-DUX4 fusion sarcoma is a round cell tumor now considered an entity separate from Ewing sarcoma with a more aggressive clinical course, occurrence in older age, and predilection to soft tissues.

SP174 Antibody Lacks Specificity for NRAS Q61R and Cross-Reacts With HRAS and KRAS Q61R Mutant Proteins in Malignant Melanoma.

HRAS, KRAS, and NRAS, highly homologous proteins, are often mutationally activated in cancer. Usually, mutations cluster in codons 12, 13, and 61 and are detected by molecular genetic testing of tumor DNA. Recently, immunohistochemistry with SP174 antibody has been introduced to detect NRAS Q61R-mutant protein.

Histopathological and genotypic characterization of metastatic colorectal carcinoma with PD-L1 (CD274)-expression: Possible roles of tumour micro environmental factors for CD274 expression.

Aberrant PD-L1 (CD274) expression has been described in different types of tumour and linked to tumour aggressiveness and a poor prognosis. In primary colorectal carcinomas (CRCs), CD274 expression was reported to be associated with mismatch repair (MMR)-deficiency, mutation, and "stem-like" immunophenotype defined by down-regulation of homeobox protein CDX2 and membranous expression of activated leukocyte cell adhesion molecule (ALCAM). However, the immunophenotype and genotype of CD274-positive metastatic CRC have not been extensively analysed.

New Mechanisms of mTOR Pathway Activation in KIT-mutant Malignant GISTs.

A great majority of gastrointestinal stromal tumors (GISTs) are primarily driven by gain-of-function KIT receptor tyrosine kinase mutations that subsequently lead to activation of phosphatidiylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, a downstream effector of KIT signaling. KIT tyrosine kinase inhibitor, imatinib mesylate, has been successfully used for the treatment of primary, advanced, and disseminated GISTs. Recently, activation of mTOR pathway independent of KIT signaling was demonstrated in imatinib mesylate naïve malignant GISTs and treatment-resistant metastatic tumors.

SP174, NRAS Q61R Mutant-Specific Antibody, Cross-Reacts With KRAS Q61R Mutant Protein in Colorectal Carcinoma.

Context: - NRAS is a member of the RAS family oncoproteins implicated in cancer. Gain-of-function NRAS mutations were reported in a subset of colorectal cancers. These mutations occur at codons 12, 13, and 61 and are detected by molecular genetic testing.

GIST Manifesting as a Retroperitoneal Tumor: Clinicopathologic Immunohistochemical, and Molecular Genetic Study of 112 Cases.

Most gastrointestinal stromal tumors (GISTs) occur in the tubular gastrointestinal (GI) tract, but some present apparently outside the GI tract. In this study, we analyzed 112 GISTs located in the retroperitoneum. These tumors occurred in 55 women and 57 men with a median age of 65 years (range: 21 to 89 y).

Prognosis of patients with BRCA1-associated ovarian carcinomas depends on TP53 accumulation status in tumor cells.

Objective: TP53 mutation is the most frequent molecular event in BRCA1-associated ovarian carcinomas. TP53 status may be a confounding factor in the evaluation of clinical importance of other proteins. We aimed to evaluate the clinical significance of BRCA1 mutations with respect to the TP53 accumulation status in 159 high-grade ovarian carcinomas.

Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas.

The CD274 (PD-L1)/PDCD1 (PD-1) pathway is crucial for the modulation of immune responses and self-tolerance. Aberrantly expressed CD274 allows tumor cells to evade host immune system and is considered to be a mechanism of adaptive immune resistance. Inhibition of the CD274/PDCD1 immune checkpoint offers a promising new therapeutic strategy.

Fumarase-deficient Uterine Leiomyomas: An Immunohistochemical, Molecular Genetic, and Clinicopathologic Study of 86 Cases.

Loss-of-function germline mutations in the fumarase (FH) gene of the Krebs cycle characterize hereditary leiomyomatosis and renal cell cancer syndrome. Fumarase (FH) deficiency can be diagnosed by the loss of immunohistochemical expression. In this study, we investigated the occurrence and clinicopathologic features of FH-deficient uterine smooth muscle tumors (SMTs).

Frequency and clinicopathologic profile of PIK3CA mutant GISTs: molecular genetic study of 529 cases.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors usually driven by the mutational activation of receptor tyrosine kinases, KIT, or PDGFRA. Oncogenic activation of phosphatidylinositide-3-kinase (PI3K), a downstream effector in the KIT signaling pathway, has been identified in different types of cancer, with the PI3K 110α subunit encoded by PIK3CA being a common mutational target. In this study, the mutational hotspot in the PIK3CA kinase domain encoded by exon 20 was evaluated in 529 imatinib-naive GISTs using PCR amplification and Sanger sequencing.

The Novel Gene CRNDE Encodes a Nuclear Peptide (CRNDEP) Which Is Overexpressed in Highly Proliferating Tissues.

CRNDE, recently described as the lncRNA-coding gene, is overexpressed at RNA level in human malignancies. Its role in gametogenesis, cellular differentiation and pluripotency has been suggested as well. Herein, we aimed to verify our hypothesis that the CRNDE gene may encode a protein product, CRNDEP.

Nuclear expression and gain-of-function β-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker.

Glomangiopericytoma (sinonasal-type hemangiopericytoma) is a rare mesenchymal neoplasm with myoid phenotype (smooth muscle actin-positive), which distinguishes this tumor from soft tissue hemangiopericytoma/solitary fibrous tumor. Molecular genetic changes underlying the pathogenesis of glomangiopericytoma are not known. In this study, 13 well-characterized glomangiopericytomas were immunohistochemically evaluated for β-catenin expression.

Detection of the BRAF V600E mutation in colon carcinoma: critical evaluation of the imunohistochemical approach.

Recently BRAF V600E mutant-specific antibody (clone VE1) became available to immunohistochemically pinpoint the occurrence of these BRAF-mutant proteins in different tumors, such as colon carcinoma. Detection of BRAF mutations is important for the accurate application of targeted therapy against BRAF serine-threonine kinase activation. In this study, we evaluated 113 colon carcinomas including 95 primary and 27 metastatic tumors with the VE1 antibody using Leica Bond-Max automated immunohistochemistry.

Cyclooxygenase-2 immunohistochemical expression in serrated polyps of the colon.

Aim Of The Study: Cyclooxygenase-2 (COX-2) expression has been observed in a substantial percentage of classical adenomas of the large bowel. The aim of the study was to assess and compare the expression of COX-2 in serrated polyps of the colon.

Material And Methods: One hundred and nineteen serrated polyps were analyzed.

p19(INK4d) mRNA and protein expression as new prognostic factors in ovarian cancer patients.

p19(INK4d) (CDKN2D) is a negative regulator of the cell cycle. Little is known of its role in cancer development and prognosis. We aimed to evaluate the clinical significance of p19(INK4d) expression in ovarian carcinomas with respect to the TP53 accumulation status, as well as the frequency of CDKN2D mutations.

Nuclear survivin expression is a positive prognostic factor in taxane-platinum-treated ovarian cancer patients.

Background: Survivin is an inhibitor of apoptosis and a regulator of mitotic progression. TP53 protein is a negative transcriptional regulator of survivin. The aim of our study was to evaluate the clinical significance of survivin expression in advanced stages ovarian cancer with respect to the TP53 status.