Browsing by Author "Vladislav, I. Tudor"

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    EP1: a novel rabbit monoclonal antibody for detection of oestrogen receptor α
    (BMJ, 2013) Badve, Sunil; Vladislav, I. Tudor; Spaulding, Betsy; Strickland, Anna; Hernandez, Sylvia; Bird-Turner, Lisa; Dodson, Cecelia; Elleby, Bjorn; Phillips, Therese; Pathology and Laboratory Medicine, School of Medicine
    Aims: Assessment of hormone receptor expression is part of routine examination of every breast cancer. In this study, we report the characterisation of a novel rabbit monoclonal antibody, clone EP1, directed against oestrogen receptor (ER) α. Additionally, its immunohistochemical performance characteristics in archival tissues are evaluated in normal tissues and two distinct cohorts of breast cancer patients. Methods: Comparative analyses between EP1 and the anti-ERα component of the ER/PR pharmDx kit (cocktail of mouse monoclonal antibody clones 1D5 and ER-2-123) and between EP1 and another commercially available rabbit monoclonal antibody, clone SP1, are described. Results: Clone EP1 specifically detects nuclear ER in all tissues examined; cytoplasmic staining was not observed. The analysis shows a high degree of concordance (~95%) between EP1 and both the ERα component of the Dako ER/PR pharmDx kit and Ventana clone SP1. However, the use of EP1 antibody together with Dako EnVision FLEX detection system resulted in a stronger staining intensity as compared with SP1 antibody using the Ventana ultraView DAB detection system resulting in better 'ease of use.' Conclusions: The use of EPI can result in better interpretation of the results of the ER analysis.
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    Gene Fusion Characterization of Rare Aggressive Prostate Cancer Variants ‐ Adenosquamous Carcinoma, Pleomorphic Giant Cell Carcinoma, and Sarcomatoid Carcinoma: An Analysis of 19 Cases
    (Wiley, 2020) Alhamar, Mohamed; Vladislav, I. Tudor; Smith, Steven C.; Gao, Yuan; Cheng, Liang; Favazza, Laura A.; Alani, Ali M.; Ittmann, Michael M.; Riddle, Nicole D.; Whitely, Lisa J.; Gupta, Nilesh S.; Carskadon, Shannon; Gomez-Gelvez, Juan C.; Chitale, Dhananjay A.; Palanisamy, Nallasivam; Hes, Ondrej; Trpkov, Kiril; Williamson, Sean R.; Pathology and Laboratory Medicine, School of Medicine
    Aims We evaluated the molecular underpinnings of rare aggressive prostate cancer variants adenosquamous, pleomorphic giant cell, and sarcomatoid carcinomas. Methods and Results We retrieved 19 tumors with one or more variant(s) and performed ERG immunohistochemistry, a next‐generation sequencing assay targeting recurrent gene fusions, and fluorescence in situ hybridization (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid (n=10), adenosquamous (n=7), and pleomorphic giant cell carcinoma (n=7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in 9 (47%, 7 via sequencing, showing TMPRSS2‐ERG and one GRHL2‐ERG fusion, and 2 via FISH, showing rearrangement via deletion). Of these, ERG immunohistochemistry was positive in the adenocarcinoma for 8/9 (89%) but only 5/9 (56%, typically decreased) in the variant. One patient had false‐positive ERG immunohistochemistry in the sarcomatoid component despite negative FISH. Two (11%) harbored BRAF fusions (FAM131A‐BRAF and SND1‐BRAF). Conclusions ERG gene fusions are present in these rare prostate cancer variants with a close frequency to conventional prostate cancer (9/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma but is less sensitive for the variant histology with weak to negative staining. Adenosquamous and sarcomatoid variants particularly can occur together. Molecular assessment may be an additional tool in select cases to confirm prostatic origin of unusual tumors. The presence of 2 BRAF gene rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1‐2% of prostate cancers.
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    Prognostic Impact of HOTAIR Expression is Restricted to ER-Negative Breast Cancers
    (Nature, 2015-03) Gökmen-Polar, Yesim; Vladislav, I. Tudor; Neelamraju, Yaseswini; Janga, Sarath Chandra; Badve, Sunil
    Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects. RNA-ISH analysis was successful in 94 cases (17% cases scored 0, 32.9% scored 1, 30.8% scored 2, and 19.1% scored 3). The expression of HOTAIR did not correlate with nodal metastasis regardless of the scoring intensity or with other study parameters (age, tumor size and grade, expression status). Further analysis of TCGA dataset showed that HOTAIR expression was lower in ductal carcinomas but higher in ER-negative tumors. Overexpression of HOTAIR was not associated with nodal metastases or prognosis in ER-positive patients. Its function as a poor prognostic indicator in ER-negative patients was restricted to node-positive patients. HOTAIR appears to be a marker for lymphatic metastases rather than hematogenous metastases in ER-negative patients.