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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detecting Her2 gene amplification has become routine in predicting therapeutic responsiveness in patients with breast carcinoma. Fluorescence in situ hybridization (FISH) is a common technique for detecting Her2 amplification, yet dark field fluorescence microscopy remains problematic for many pathologists. Thus, a technique such as chromogenic in situ hybridization (CISH), in which the more familiar light microscopy can be used, is appealing. Paraffin-embedded sections from 61 breast carcinomas were tested for Her2 amplification by immunohistochemistry (IHC) and CISH. FISH was used to confirm CISH results. Excellent correlation was found between IHC and CISH except in cases considered negative (1+ on the DAKO scale) by IHC. CISH detected low-level Her2 amplification in 4 of 9 of these cases. Amplification was subsequently confirmed by FISH in all but 1 case. When compared with FISH, CISH was more sensitive than IHC for detecting low levels of Her2 gene amplification. Moreover, excellent concordance was found between FISH and CISH, supporting the conclusion that the CISH assay for Her2 gene amplification provides an accurate, effective, and practical alternative to FISH.
Appl Immunohistochem Mol Morphol 2004 Sep
PMID:Her2 amplification: correlation of chromogenic in situ hybridization with immunohistochemistry and fluorescence in situ hybridization. 1555 39

Paraffin-embedded tissue is an important source of material for molecular pathology and genetic investigations. We used DNA isolated from microdissected formalin-fixed, paraffin-embedded gastric tumors for mutation analysis of a region of the human gene for uracil-DNA glycosylase (UNG), encoding the UNG catalytic domain, and detected apparent base substitutions which, after further investigation, proved to be polymerase chain reaction (PCR) artifacts. We demonstrate that low DNA template input in PCR can generate false mutations, mainly guanine to adenine transitions, in a sequence-dependent manner. One such mutation is identical to a mutation previously reported in the UNG gene in human glioma. This phenomenon was not caused by microheterogeneity in the sample material because the same artifact was seen after amplification of a homogenous, diluted plasmid. We did not observe genuine mutations in the UNG gene in 16 samples. Our results demonstrate that caution should be taken when interpreting data from PCR-based analysis of somatic mutations using low amounts of template DNA, and that methods used to enrich putative subpopulations of mutant molecules in a sample material could, in essence, be a further amplification of sequence-dependent PCR-generated artifacts.
J Mol Diagn 2005 Feb
PMID:Low copy number DNA template can render polymerase chain reaction error prone in a sequence-dependent manner. 2620 Feb 90

Paraffin-embedded sections of various adenocarcinomas (13 colonic, 11 mucinous ovarian, 5 serous ovarian, 8 pancreatic, 6 ampullary, 12 gastric, 5 esophageal, 10 endometrial, 29 breast, and 55 lung) and 29 additional lung carcinomas (nonadenocarcinomas) were immunostained with antibodies to CDX2 protein, cytokeratin 7 (CK7), and cytokeratin 20 (CK20). The 84 lung carcinomas were also stained with antibody to thyroid transcription factor-1 (TTF-1). All colorectal and most ovarian mucinous carcinomas were strongly and diffusely immunoreactive for CDX2. Esophageal, gastric, and ampullary adenocarcinomas showed variable immunoreactivity for CDX2. All breast, nonmucinous ovarian, and most endometrial and pancreatic adenocarcinomas showed no immunoreactivity for CDX2. CK7 and CK20 expression was similar to previous reports. Ten of 84 primary lung carcinomas (12%) were immunoreactive for CDX2 expression. Of these, 5 (4 adenocarcinomas and 1 large cell carcinoma) were reactive for TTF-1. Gene expression profiling data--available for 32 of these 84 tumors--showed CDX2 gene expression in 7 of 8 (88%) CDX2 immunoreactive tumors whereas only 1 of 24 (4%) tumors negative for CDX2 immunoreactivity showed CDX2 gene expression. The authors conclude that CDX2 is a relatively specific marker for tumors with intestinal differentiation, with the caveat that its expression can be seen in primary large cell and adenocarcinomas of the lung and mucinous carcinomas of the ovary.
Appl Immunohistochem Mol Morphol 2005 Mar
PMID:CDX2 immunostaining as a gastrointestinal marker: expression in lung carcinomas is a potential pitfall. 1678 99

We report the use of molecular techniques in the diagnosis of a case of culture-negative necrotizing fasciitis occurring in a 32-year-old female with no significant past medical history and who died within 36 hours of admission. Paraffin-embedded tissue sections from the popliteal fossa region obtained at autopsy showed hemorrhage, necrosis, and mild inflammation by hematoxylin and eosin staining. Tissue gram stain showed numerous gram-positive organisms arranged in clusters. The sequences of the first 500 bp of bacterial 16S rRNA gene amplified from the lesion were identical to a Lancefield group A beta-hemolytic Streptococcus pyogenes. Streptococcal pyrogenic exotoxin A and B superantigen genes were detected and an emm type 1 was determined by polymerase chain reaction and sequencing from the lesion. This confirmed the etiology of the patient's rapid deterioration with multisystem organ failure.
J Mol Diagn 2005 Nov
PMID:Molecular diagnosis of necrotizing fasciitis by 16S rRNA gene sequencing and superantigen gene detection. 1625 64

Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-beta1 resulting in myofibroblastic transformation. 11Beta-HSD2 in concert appears to modulate the severity of endometrial fibrosis.
Mol Cell Endocrinol 2006 Mar 27
PMID:Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities. 1640 51

The aim of this study was to evaluate the role of retinoblastoma protein (pRb), alone and in combination with p16, as a predictive marker for metastases in non-sentinel nodes in cases where the sentinel node showed metastatic breast carcinoma. Paraffin blocks of lymph nodes from 48 patients with metastatic breast carcinoma were immunostained with a monoclonal antibody to retinoblastoma protein (PharMingen). Results were compared with known prognostic parameters of the primary tumor, estrogen and progesterone receptor status, proliferation index, and p16 (DAKO) expression. Lymph nodes from 38 of the 48 (79%) cases were pRb positive. There was no correlation of pRb staining alone with the primary tumor parameters studied or the proliferative index of the metastatic tumor. In 16 patients with both a sentinel node biopsy and an axillary lymph node dissection, 8 (50%) had metastatic breast carcinoma. The sentinel nodes of three of these eight patients (38%) were pRb negative (positive predictive value of 60% vs. 73% for p16). The remaining eight patients (50%) had no metastases in non-sentinel nodes, even though their sentinel nodes had metastatic breast carcinoma; six of these eight patients (75%) were pRb positive (negative predictive value of 55% vs. 83% for p16). pRb and p16 staining results combined showed that pRb-negative/p16-positive cases were associated with non-sentinel node metastases (positive predictive value of 100%) as well as poor prognostic parameters. Patients with the opposite staining profile (pRb positive and p16 negative) were mostly without non-sentinel node metastases (negative predictive value of 75%). Cases negative for both pRb and p16 were consistently associated with a better prognostic phenotype and absence of additional axillary node metastases. In conclusion, the presence or absence of pRb in sentinel nodes is of little predictive value for non-sentinel node metastases unless taken in conjunction with the presence of p16 staining. Instead, it appears to enhance the positive predictive value of p16 in determining the presence of non-sentinel node metastases. Due to the limited subgroup sample size in this study, clinical guidelines cannot be suggested as yet, but further research focused on the pRb-negative/p16-positivie and pRb-negative/p16-negative phenotypes may yield beneficial results.
Appl Immunohistochem Mol Morphol 2006 Mar
PMID:Expression of retinoblastoma protein in breast cancer metastases to sentinel nodes: evaluation of its role as a marker for the presence of metastases in non-sentinel axillary nodes, and comparison to p16INK4a. 1654 Jul 33

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.
Appl Immunohistochem Mol Morphol 2006 Mar
PMID:Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas. 1654 Jul 40

Aim-To examine the expression of CD40 and B7 (CD80) antigens and the CD40 ligand in Hodgkin's disease.Methods-Antigen and ligand expression was studied in 17 cases of Hodgkin's disease using immunohistochemistry. The study included 11 cases of Hodgkin's disease in which latent Epstein-Barr virus (EBV) infection could be demonstrated within tumour cells by in situ hybridisation for the EBV encoded early RNAs (EBERs).Results-In all cases, irrespective of EBV status, Reed-Sternberg cells and their variants (HRS cells) showed strong expression of both B7 and CD40 antigens. CD40 ligand expression was not shown in HRS cells but was confined to a subset of small lymphocytes some of which were seen to be in intimate contact with HRS cells.Paraffin wax sections from a further 60 cases of Hodgkin's disease were examined for CD40 and EBER expression alone. The CD40 antigen was identified in HRS cells in all of these cases irrespective of EBER expression.Conclusions-As CD40 and B7 expression are features of professional antigen presenting cells, these results provide further evidence that HRS cells may have antigen presenting properties and that this may contribute to the characteristic recruitment and activation of non-malignant lymphocytes which is a feature of Hodgkin's disease. The ability of HRS cells to activate T(h) cells may in turn contribute to their own survival through the induction of the gp39/CD40 pathway.
Clin Mol Pathol 1995 Apr
PMID:Expression of B7 (CD80) and CD40 antigens and the CD40 ligand in Hodgkin's disease is independent of latent Epstein-Barr virus infection. 1669 80

Aim-To establish whether testicular germ cell tumours contain Epstein-Barr virus (EBV) and if so to provide further evidence for the hypothesis that EBV plays a direct role in the pathogenesis of testicular germ cell tumours.Method-Paraffin wax embedded tissue blocks from 21 germ cell tumours including 12 teratomas and nine classic seminomas were examined by in situ hybridisation for the expression of the small EBV encoded nuclear RNA transcripts (EBER-1 and -2) using isotopic and nonisotopic probes.Results-There was no EBER specific signal detectable in any of the testicular germ cell tumours examined by in situ hybridisation whilst a strong signal was observed in appropriate control sections.Conclusion-The absence of demonstrable EBER transcripts in testicular germ cell tumours make a direct role for EBV in the pathogenesis of these tumours unlikely. Other explanations for the epidemiological and serological evidence linking EBV with germ cell tumours need to be explored.
Clin Mol Pathol 1995 Apr
PMID:Absence of Epstein-Barr virus in testicular germ cell tumours: a study of 21 cases using in situ hybridisation. 1669 81

Aim-To investigate the expression of p53 protein in invasive squamous cell carcinoma (SCC) of the larynx and dysplasia in relation to histological grade and tobacco smoking.Method-Paraffin wax embedded tissue sections from 41 cases of invasive SCC of the larynx, 28 cases of dysplasia and 14 control laryngeal biopsy specimens were studied immunohistochemically using two anti-p53 monoclonal antibodies (DO7 and 1801). The Streptavidin/horseradish peroxidase method was used after microwave antigen retrieval and a semiquantitative method was applied to assess the extent of p53 expression.Results-Of the cases of invasive SCC of the larynx, 78% (32/41), regardless of histological grade, overexpressed p53 compared with only 30% (eight of 28) of cases of mild dysplasia. A gradual increase in p53 expression from mild to severe dysplasia (60%) was observed, and only three of 14 control biopsy specimens of laryngeal nodules showed occasional weakly positive basal cells.Conclusion-The gradual increase in p53 expression from mild to severe dysplasia to invasive SCC indicates that p53 overexpression is an early event in laryngeal carcinogenesis which may lead to invasive malignancy. p53 overexpression may be related to environmental factors as most of the patients smoked tobacco. Microwave postfixation may be essential for the reliable detection of p53.
Clin Mol Pathol 1995 Aug
PMID:p53 Overexpression in laryngeal squamous cell carcinoma and dysplasia. 1669 5


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