Browsing by Author "Cheville, John C."

Now showing 1 - 3 of 3
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    CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: implications for epigenetic therapy
    (American Association for Cancer Research, 2014-04-01) Ding, Liya; Chen, Shuai; Liu, Ping; Pan, Yunqian; Zhong, Jian; Regan, Kevin M.; Wang, Liguo; Yu, Chunrong; Rizzardi, Tony; Cheng, Liang; Zhang, Jun; Schmechel, Stephen C.; Cheville, John C.; van Deursen, Jan; Tindall, Donald J.; Huang, Haojie; Department of Pathology & Laboratory Medicine, IU School of Medicine
    Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbppc−/−;Ptenpc+/− mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp−/−;Pten+/− and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones, in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27KIP1 and p21CIP1. Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbppc−/−;Ptenpc+/− mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic targeted therapy in prostate cancer patients.
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    New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia
    (Elsevier, 2021) Trpkov, Kiril; Hes, Ondrej; Williamson, Sean R.; Adeniran, Adebowale J.; Agaimy, Abbas; Alaghehbandan, Reza; Amin, Mahul B.; Argani, Pedram; Chen, Ying-Bei; Cheng, Liang; Epstein, Jonathan I.; Cheville, John C.; Comperat, Eva; Werneck da Cunha, Isabela; Gordetsky, Jennifer B.; Gupta, Sounak; He, Huiying; Hirsch, Michelle S.; Humphrey, Peter A.; Kapur, Payal; Kojima, Fumiyoshi; Lopez, Jose I.; Maclean, Fiona; Magi-Galluzzi, Cristina; McKenney, Jesse K.; Mehra, Rohit; Menon, Santosh; Netto, George J.; Przybycin, Christopher G.; Rao, Priya; Rao, Qiu; Reuter, Victor E.; Saleeb, Rola M.; Shah, Rajal B.; Smith, Steven C.; Tickoo, Satish; Tretiakova, Maria S.; True, Lawrence; Verkarre, Virginie; Wobker, Sara E.; Zhou, Ming; Gill, Anthony J.; Pathology and Laboratory Medicine, School of Medicine
    The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.
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    Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer
    (SpringerNature, 2015-05) Amin, Mahul B.; Smith, Steven C.; Reuter, Victor E.; Epstein, Jonathan I.; Grignon, David J.; Hansel, Donna E.; Lin, Oscar; McKenney, Jesse K.; Montironi, Rodolfo; Paner, Gladell P.; Al-Ahmadie, Hikmat A.; Algaba, Ferran; Ali, Syed; Alvarado-Cabrero, Isabel; Bubendorf, Lukas; Cheng, Liang; Cheville, John C.; Kristiansen, Glen; Cote, Richard J.; Delahunt, Brett; Eble, John N.; Genega, Elizabeth M.; Gulmann, Christian; Hartmann, Arndt; Langner, Cord; Lopez-Beltran, Antonio; Magi-Galluzzi, Cristina; Merce, Jorda; Netto, George J.; Oliva, Esther; Rao, Priya; Ro, Jae Y.; Srigley, John R.; Tickoo, Satish K.; Tsuzuki, Toyonori; Umar, Saleem A.; Van der Kwast, Theo; Young, Robert H.; Soloway, Mark S.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.