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https://www.readbyqxmd.com/read/28524003/targeting-the-programmed-cell-death-1-pathway-in-genitourinary-tumors-current-progress-and-future-perspectives
#1
Rodolfo Montironi, Liang Cheng, Holger Moch, Antonio Lopez-Beltran, Marina Scarpelli, Francesco Massari, Michelangelo Fiorentino, Chiara Ciccarese, Michael Koch, Hristos Z Kaimakliotis, Lisha Wang, Roberto Pili, Steven A Mann
Immune checkpoint inhibitors have revolutionized the treatment many malignancies with over a dozen new United States Food and Drug Administration (FDA) approvals in the past six years. Due to the combination of potent treatment success and potentially deadly adverse effects from immune checkpoint inhibitors, gathering prognostic and predictive information about FDA-indicated tumors is prudent. PD-L1 expression is a poor prognostic factor and predictive of better responses from both PD-1 and PD-L1 inhibitors in a variety of tumor types including RCC and urothelial carcinoma...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28503092/management-of-gene-variants-of-unknown-significance-analysis-method-and-risk-assessment-of-the-vhl-mutation-p-p81s-c-241c-t
#2
REVIEW
Daniela Alosi, Marie Luise Bisgaard, Sophie Nowak Hemmingsen, Lotte Nylandsted Krogh, Hanne Birte Mikkelsen, Marie Louise Mølgaard Binderup
BACKGROUND: Evaluation of the pathogenicity of a gene variant of unknown significance (VUS) is crucial for molecular diagnosis and genetic counseling, but can be challenging. This is especially so in phenotypically variable diseases, such as von Hippel-Lindau disease (vHL). vHL is caused by germline mutations in the VHL gene, which predispose to the development of multiple tumors such as central nervous system hemangioblastomas and renal cell carcinoma (RCC). OBJECTIVE: We propose a method for the evaluation of VUS pathogenicity through our experience with the VHL missense mutation c...
February 2017: Current Genomics
https://www.readbyqxmd.com/read/28464919/the-role-of-apoptosis-repressor-with-a-card-domain-arc-in-the-therapeutic-resistance-of-renal-cell-carcinoma-rcc-the-crucial-role-of-arc-in-the-inhibition-of-extrinsic-and-intrinsic-apoptotic-signalling
#3
Csaba Toth, Sarah Funke, Vanessa Nitsche, Anna Liverts, Viktoriya Zlachevska, Marcia Gasis, Constanze Wiek, Helmut Hanenberg, Csaba Mahotka, Peter Schirmacher, Sebastian Heikaus
BACKGROUND: Renal cell carcinomas (RCCs) display broad resistance against conventional radio- and chemotherapies, which is due at least in part to impairments in both extrinsic and intrinsic apoptotic pathways. One important anti-apoptotic factor that is strongly overexpressed in RCCs and known to inhibit both apoptotic pathways is ARC (apoptosis repressor with a CARD domain). METHODS: Expression and subcellular distribution of ARC in RCC tissue samples and RCC cell lines were determined by immunohistochemistry and fluorescent immunohistochemistry, respectively...
May 2, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28449664/distinct-immunophenotypes-and-prognostic-factors-in-renal-cell-carcinoma-with-sarcomatoid-differentiation-a-systematic-study-of-19-immunohistochemical-markers-in-42-cases
#4
Wenjuan Yu, Yuewei Wang, Yanxia Jiang, Wei Zhang, Yujun Li
BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid differentiation is a relatively rare tumor containing both carcinoma and sarcomatoid components. However, there has not been a systemic study on immunophenotypes of renal cell carcinoma with sarcomatoid differentiation, especially using some renal specific immunohistochemical markers. In this study, we aimed to comprehensively investigate the distinct immunophenotypes of RCC with sarcomatoid differentiation to analyze the pathogenesis of sarcomatoid differentiation and identify new prognostic factors in RCC with sarcomatoid differentiation...
April 27, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28416106/categorizing-renal-oncocytic-neoplasms-on-core-needle-biopsy-a-morphologic-and-immunophenotypic-study-of-144-cases-with-clinical-follow-up-alderman-ma-daignault-s-wolf-js-jr-palapattu-gs-weizer-az-hafez-ks-kunju-lp-wu-aj-hum-pathol-september-2016-55-1-10
#5
Oleksandr N Kryvenko
There is limited literature on renal oncocytic neoplasms diagnosed on core biopsy. All renal oncocytic neoplasm core biopsies from 2006 to 2013 were, retrospectively, reviewed. Morphologic features and an immunohistochemical panel of CK7, c-KIT, and S100A1 were assessed. Concordance with resection diagnosis, statistical analysis including a random forest classification, and follow-up were recorded. The postimmunohistochemical diagnoses of 144 renal oncocytic core biopsies were favor oncocytoma (67%), favor renal cell carcinoma (RCC) (12%), and cannot exclude RCC (21%)...
April 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28415646/combination-of-immunohistochemistry-fish-and-rt-pcr-shows-high-incidence-of-xp11-translocation-rcc-comparison-of-three-different-diagnostic-methods
#6
Hyun Jung Lee, Dong Hoon Shin, Gyu You Noh, Young Keum Kim, Ahrong Kim, Nari Shin, Jung Hee Lee, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Mee Young Sol, Seo Hee Rha, Sung Woo Park
We evaluated the frequency of translocation renal cell carcinoma (RCC) by reverse transcription polymerase chain reaction (RT-PCR) and how well the TFE3 immunoreactivity is concordant with TFE3 gene translocation status proved by fluorescence in situ hybridization (FISH) assay and RT-PCR. TFE3 and Cathepsin K expression was analyzed by immunohistochemistry in 185 RCC cases, and 48 cases either of more than weak expression of TFE3 or of positivity for Cathepsin K were done for FISH analysis and RT-PCR. All the RT-PCR positive cases were confirmed by cloning and sequencing...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404922/adipophilin-as-prognostic-biomarker-in-clear-cell-renal-cell-carcinoma
#7
Yuri Tolkach, Christine Lüders, Sebastian Meller, Klaus Jung, Carsten Stephan, Glen Kristiansen
OBJECTIVE: To study the expression of adipophilin (PLIN2), a lipid storage-associated cell protein, in different subtypes of renal cell cancer and to elucidate its prognostic value. MATERIALS AND METHODS: Two-hundred-seventy-five patients with renal cell carcinoma (RCC) were included in this study. Immunohistochemistry with a polyclonal antibody to adipophilin was used on the tissue microarray (formalin-fixed, paraffin-embedded tissue) for detection of adipophilin...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28393205/high-annexin-a5-expression-promotes-tumor-progression-and-poor-prognosis-in-renal-cell-carcinoma
#8
Jingyuan Tang, Zhiqiang Qin, Peng Han, Wei Wang, Chengdi Yang, Zhen Xu, Ran Li, Bianjiang Liu, Chao Qin, Zengjun Wang, Min Tang, Wei Zhang
Annexin A5 has been found to act as an oncogenic protein in a variety of cancers. However, its specific biological role and mechanism in renal cell cancer (RCC) remains unknown. Quantitative Real-time PCR and western blotting were used to evaluate the mRNA and protein expression level of Annexin A5 in human RCC cell lines and tissues. Immunohistochemistry was adopted to measure the Annexin A5 expression in 123 cases of RCC tissues. Survival analysis was performed to explore the association between Annexin A5 expression and the prognosis of RCC...
April 3, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28353093/pd-l2-a-prognostic-marker-in-chromophobe-renal-cell-carcinoma
#9
Franziska Erlmeier, Wilko Weichert, Michael Autenrieth, Max Wiedemann, Andres Jan Schrader, Arndt Hartmann, Philipp Ivanyi, Sandra Steffens
In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma. In contrast, little is known about PD-L2 expression patterns in RCC, especially in rarer subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-L2 expression in chromophobe (ch)RCC. Eighty-one patients who underwent renal surgery due to chRCC were retrospectively evaluated...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28349447/overexpression-of-placenta-specific-8-is-associated-with-malignant-progression-and-poor-prognosis-of-clear-cell-renal-cell-carcinoma
#10
Liping Shi, Long Xiao, Baoli Heng, Shijie Mo, Weijun Chen, Zexuan Su
BACKGROUND: Placenta specific 8 (PLAC8) plays an important role in many different cellular processes and human diseases, including multiple types of cancer. However, the functional role of PLAC8 in clear cell renal cell carcinoma (ccRCC) has never been elucidated. METHODS: PLAC8 mRNA expression was investigated in 31 pairs of fresh ccRCC tumor tissues and matched adjacent non-tumor tissues by RT-qPCR and confirmed by analyzing the TCGA KRCC dataset which contains RNA-seq data of 534 ccRCC and 72 solid normal tissues...
March 27, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28300276/reassessing-the-clinical-spectrum-associated-with-hereditary-leiomyomatosis-and-renal-cell-carcinoma-syndrome-in-french-fh-mutation-carriers
#11
M Muller, S Ferlicot, M Guillaud-Bataille, G Le Teuff, C Genestie, S Deveaux, A Slama, N Poulalhon, B Escudier, L Albiges, N Soufir, M-F Avril, B Gardie, C Saldana, Y Allory, A-P Gimenez-Roqueplo, B Bressac-de Paillerets, S Richard, P R Benusiglio
We addressed uncertainties regarding hereditary leiomyomatosis and renal cell carcinoma (HLRCC) by exploring all French cases, representing the largest series to date. Fumarate hydratase (FH) germline testing was performed with Sanger sequencing and qPCR/MLPA. Enzyme activity was measured when necessary. We carried out whenever possible a pathology review of RCC and S-(2-succino)-cysteine (2SC)/fumarate hydratase immunohistochemistry. We estimated survival using non-parametric Kaplan-Meier. There were 182 cases from 114 families...
March 16, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28296677/rbm10-tfe3-renal-cell-carcinoma-a-potential-diagnostic-pitfall-due-to-cryptic-intrachromosomal-xp11-2-inversion-resulting-in-false-negative-tfe3-fish
#12
MULTICENTER STUDY
Pedram Argani, Lei Zhang, Victor E Reuter, Satish K Tickoo, Cristina R Antonescu
Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion...
May 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28288038/immunohistochemical-characterization-of-fumarate-hydratase-fh-and-succinate-dehydrogenase-sdh-in-cutaneous-leiomyomas-for-detection-of-familial-cancer-syndromes
#13
Cody S Carter, Stephanie L Skala, Arul M Chinnaiyan, Jonathan B McHugh, Javed Siddiqui, Xuhong Cao, Saravana M Dhanasekaran, Douglas R Fullen, Amir Lagstein, May P Chan, Rohit Mehra
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by germline mutations in the FH gene, and is associated with increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma (HLRCC-associated RCC). Absent immunohistochemical expression of fumarate hydratase (FH) has previously been used to diagnose HLRCC-associated RCC, but immunohistochemical staining of leiomyomas is not standard practice. We performed immunohistochemistry (IHC) on whole sections from consecutive cutaneous leiomyomas from our archives to evaluate for both FH and succinate dehydrogenase B expression, in addition to clinicopathologic data collection and review of all hematoxylin and eosin-stained slides for blinded morphologic evaluation of features reported to be seen in HLRCC-associated uterine leiomyomas...
June 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28249616/tumor-to-tumor-metastases-papillary-thyroid-carcinoma-into-a-clear-cell-renal-cell-carcinoma
#14
Jin Soo Andy Song, S Mark Taylor, Jonathan Trites, Matthew H Rigby, Martin Joseph Bullock, Jennifer Merrimen, Ricardo Rendon, Robert D Hart
BACKGROUND: Thyroid metastases to distant sites are uncommon incidents, most often metastasizing to the lungs and bones. Rates of metastasis to the kidney are particularly low, ranging from 2.8-3.8% for papillary and 6-20% for follicular variants of well-differentiated thyroid cancers (WDTCs). In rare instances, tumor-to-tumor metastasis between two true primary neoplasms can occurs. This medical phenomenon has previously occurred as a clear cell renal cell carcinoma (CCRCC) spreading to a WDTC...
March 1, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28052770/a-systematic-search-strategy-identifies-cubilin-as-independent-prognostic-marker-for-renal-cell-carcinoma
#15
Gabriela Gremel, Dijana Djureinovic, Marjut Niinivirta, Alexander Laird, Oscar Ljungqvist, Henrik Johannesson, Julia Bergman, Per-Henrik Edqvist, Sanjay Navani, Naila Khan, Tushar Patil, Åsa Sivertsson, Mathias Uhlén, David J Harrison, Gustav J Ullenhag, Grant D Stewart, Fredrik Pontén
BACKGROUND: There is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC). METHODS: Human Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers...
January 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28050384/inflammatory-myofibroblastic-tumor-of-the-kidney-a-rare-renal-tumor
#16
Alvin Jose Pothadiyil, Suresh Bhat, Fredrick Paul, Jithesh Mampatta, Mahesh Srinivas
Inflammatory Myofibroblastic Tumour (IMT) or 'pseudotumour' of the kidney is a rare benign tumour of unknown aetiology affecting mostly young adults. A subset of IMT is neoplastic and harbours translocations of activin receptor-like kinase-1 (ALK-1) gene and can recur or rarely metastasize. Presentation varies from an incidentaloma to gross haematuria. Clinical examination and radiological investigations are usually inconclusive. Often, biopsy is inconclusive necessitating a management similar to that of Renal Cell Cancer (RCC)...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28035577/c-met-in-chromophobe-renal-cell-carcinoma
#17
Franziska Erlmeier, Philipp Ivanyi, Arndt Hartmann, Michael Autenrieth, Max Wiedemann, Wilko Weichert, Sandra Steffens
c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28011500/a-study-of-angiogenesis-markers-in-patients-with-renal-cell-carcinoma-undergoing-therapy-with-sunitinib
#18
Clive Stubbs, Antonio D Bardoli, Mehran Afshar, Sarah Pirrie, Manuela Miscoria, Isabella Wheeley, Emilio Porfiri
BACKGROUND: Sunitinib is a tyrosine kinase inhibitor (TKI) targeting tumour angiogenesis in patients with advanced renal cell carcinoma (RCC). Currently no universally agreed model exists correlating the expression of angiogenesis markers with the success of treatment. PATIENTS AND METHODS: We retrospectively analysed archival tissue for 59 RCC patients treated with sunitinib. The expression of angiogenesis markers VEGF-A, VEGFR, PDGFββ, PDGFR, CCND1 and CA9 was assessed by immunohistochemistry (IHC) and correlated with overall survival (OS) and progression-free survival (PFS)...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28009604/renal-cell-carcinoma-with-chromosome-6p-amplification-including-the-tfeb-gene-a-novel-mechanism-of-tumor-pathogenesis
#19
Sean R Williamson, David J Grignon, Liang Cheng, Laura Favazza, Dibson D Gondim, Shannon Carskadon, Nilesh S Gupta, Dhananjay A Chitale, Shanker Kalyana-Sundaram, Nallasivam Palanisamy
Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K...
March 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27906674/nuclear-localization-of-the-ck2%C3%AE-subunit-correlates-with-poor-prognosis-in-clear-cell-renal-cell-carcinoma
#20
Maj Rabjerg, Barbara Guerra, Aida Oliván-Viguera, Minne Line Nedergaard Mikkelsen, Ralf Köhler, Olaf-Georg Issinger, Niels Marcussen
Protein kinase CK2α, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2α expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC)...
January 3, 2017: Oncotarget
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