Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients.

Purpose: Various aberrations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3 are found in different cancers, including breast cancer (BC). This study analyzed the impact of FGFR amplification on the BC prognosis.

Methods: The study included 894 BC patients.

HER2 FISH results in breast cancers with increased CEN17 signals using alternative chromosome 17 probes - reclassifying cases in the equivocal category.

Aims: HER2 testing of invasive breast cancer by in-situ hybridization guides therapy decisions. Probing HER2 and centromere of chromosome 17 (cen17) simultaneously is supposed to reveal both a potential HER2 gene amplification and polysomy 17. However, a considerable number of breast cancer patients with quasi polysomy 17 are considered 'equivocal', which is diagnostically meaningless.

BIRC3 alterations in chronic and B-cell acute lymphocytic leukemia patients.

Deletions within chromosome 11q22-23, are considered among the most common chromosomal aberrations in chronic lymphocytic leukemia (CLL), and are associated with a poor outcome. In addition to the ataxia telangiectasia mutated () gene, the baculoviral IAP repeat-containing 3 () gene is also located in the region. encodes a negative regulator of the non-canonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein.

The FlexISH assay brings flexibility to cytogenetic HER2 testing.

Aims: Fluorescence in-situ hybridization (FISH) is the method of choice for quantitative human epidermal growth factor receptor 2 (HER2) (also known as ERBB2) gene testing in invasive breast cancer. HER2 testing has great clinical impact, and is often claimed to expeditiously complete the entire diagnostic procedure for an individual patient. Against this background, the aim of this study was to evaluate the usefulness and performance of a novel dual-colour HER2/cen17 FISH assay designed to facilitate flexible (overnight) and rapid (<2 h of hybridization) FISH.

Fibroblast growth factor receptor (FGFR) gene amplifications are rare events in bladder cancer.

Aims: Activating point mutations and protein overexpression of fibroblast growth factor receptors (FGFRs), especially FGFR3, are frequent events in bladder cancer. Little is known about gene amplifications, therefore we characterized amplification of FGFR1-3 by fluorescence in-situ hybridization (FISH).

Methods And Results: Tumours of 153 patients (n = 65 pTa low-grade, n = 15 pTa high-grade, n = 37 pT1, n = 20 pT2, n = 10 pT3, n = 6 pT4) were analysed by FISH for FGFR1-3 copy numbers and screened for FGFR3 mutations and immunohistochemical protein expression.

Chromogenic in situ hybridization is a reliable assay for detection of ALK rearrangements in adenocarcinomas of the lung.

Reliable detection of anaplastic lymphoma kinase (ALK) rearrangements is a prerequisite for personalized treatment of lung cancer patients, as ALK rearrangements represent a predictive biomarker for the therapy with specific tyrosine kinase inhibitors. Currently, fluorescent in situ hybridization (FISH) is considered to be the standard method for assessing formalin-fixed and paraffin-embedded tissue for ALK inversions and translocations. However, FISH requires a specialized equipment, the signals fade rapidly and it is difficult to detect overall morphology and tumor heterogeneity.

Molecular and clinicopathological analysis of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous tumor of intermediate malignancy. The most remarkable cytogenetic feature of DFSP is the chromosomal translocation t(17;22)(q22;q13), causing a fusion of the platelet-derived growth factor beta chain (PDGFB) gene at 22q13, and the collagen type 1 alpha 1 (COL1A1) at 17q22. The aim of the study was to analyze the molecular characteristic of DFSP in conjunction with histopathological and clinical features.

Losses of 3p14 and 9p21 as shown by fluorescence in situ hybridization are early events in tumorigenesis of oral squamous cell carcinoma and already occur in simple keratosis.

Tumorigenesis of oral squamous cell carcinoma (OSCC) has been postulated to represent a multistep process driven by the accumulation of carcinogen-induced genetic changes. Alterations of the 3p14 fragile site containing the fragile histidine triade gene and of the 9p21 tumor suppressor locus containing methylthioadenosine phosphorylase, p16 and p15 characteristically occur in oral leukoplakia, a known precursor of OSCC, and are at present considered to indicate the transition from simple keratosis (hyperplasia) to dysplasia. The aim of the study was to evaluate the occurrence of losses of 3p14 and 9p21 and to evaluate polysomies 3 and 9 in leukoplakias using highly sensitive fluorescence in situ hybridization (FISH) probes.

HMGA1 proteins in human atherosclerotic plaques.

One of the major characteristics of atherosclerosis is the migration of smooth muscle cells (SMC) from the tunica media to the intima, caused by alterations in the environment, e.g. mechanical, chemical, or immunologic injuries of the arterial walls.

Extensive expression studies revealed a complex alternative splicing pattern of the HMGA2 gene.

Chromosomal rearrangements of the HMGA2 locus belong to the most common aberrations in human benign tumors. HMGA2 rearrangements often result in chimeric genes expressing transcripts consisting of the first three exons of HMGA2 followed by ectopic sequences derived from intron 3 of that gene. RT-PCR-based expression studies of 4 of these HMGA2 transcripts revealed a co-expression with the "wild-type" HMGA2a in tumor samples as well as in normal tissues.

Angiogenetic signaling through hypoxia: HMGB1: an angiogenetic switch molecule.

The initiation of angiogenesis, called the angiogenetic switch, is a crucial early step in tumor progression and propagation, ensuring an adequate oxygen supply. The rapid growth of tumors is accompanied by a reduced microvessel density, resulting in chronic hypoxia that often leads to necrotic areas within the tumor. These hypoxic and necrotic regions exhibit increased expression of angiogenetic growth factors, eg, vascular endothelial growth factor, and may also attract macrophages, which are known to produce a number of potent angiogenetic cytokines and growth factors.

Expression pattern of the HMGB1 gene in sarcomas of the dog.

Background: The human high mobility group protein B1 (HMGB1) has attracted considerable interest among oncologists because it sensitises cancer cells to the anticancer drug cisplatin by shielding cisplatin-DNA adducts from nucleotide excision repair.

Materials And Methods: Since cisplatin is the cornerstone of adjuvant systemic therapy for osteosarcomas, in both humans and dogs, the expression pattern of the HMGB1 gene in seven canine sarcomas was investigated by Northern blot analysis and semi-quantitative RT-PCR.

Results: A strong intertumoural variation of HMGB1 expression was detected by Northern blot analysis and confirmed by the semi-quantitative RT-PCR established herein.

Tissue-specific expression patterns of the RAGE receptor and its soluble forms--a result of regulated alternative splicing?

The receptor for advanced glycation end products (RAGE) is known to be causally involved in a variety of pathophysiological processes, e.g. immune/inflammatory disorders, Alzheimer disease, tumors, and abnormalities associated with diabetes as arteriosclerosis or disordered wound healing.

Sequencing of intron 3 of HMGA2 uncovers the existence of a novel exon.

Aberrations affecting the gene encoding the high mobility group protein HMGA2 (formerly HMGIC) have been found in a variety of human tumors, e.g., uterine leiomyomas, lipomas, and pulmonary chondroid hamartomas.