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Hadis Honarvar, Javad Garousi, Elin Gunneriusson, Ingmarie Höidén-Guthenberg, Mohamed Altai, Charles Widström, Vladimir Tolmachev, Fredrik Y Frejd
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme involved in regulation of tissue pH balance. In cancer, CAIX expression is associated with tumor hypoxia. CAIX is also overexpressed in renal cell carcinoma and is a molecular target for the therapeutic antibody cG250 (girentuximab). Radionuclide imaging of CAIX expression might be used for identification of patients who may benefit from cG250 therapy and from treatment strategies for hypoxic tumors. Affibody molecules are small (7 kDa) scaffold proteins having a high potential as probes for radionuclide molecular imaging...
February 2015: International Journal of Oncology
Karim Chamie, Pia Klöpfer, Paul Bevan, Stephan Störkel, Jonathan Said, Barbara Fall, Arie S Belldegrun, Allan J Pantuck
INTRODUCTION AND OBJECTIVE: With a limited number of prognostic and predictive biomarkers available, carbonic anhydrase-IX (CAIX) has served as an important prognostic biomarker for patients with clear cell renal cell carcinoma (ccRCC). However, studies have recently called into question the role of CAIX as a biomarker for ccRCC. To investigate this uncertainty, we quantified the association of CAIX with lymphatic involvement and survival using data from ARISER study (WX-2007-03-HR)--a prospective trial involving subjects with high-risk nonmetastatic ccRCC...
May 2015: Urologic Oncology
Constantijn H J Muselaers, Mark Rijpkema, Desirée L Bos, Johan F Langenhuijsen, Wim J G Oyen, Peter F A Mulders, Egbert Oosterwijk, Otto C Boerman
PURPOSE: Tumor targeted optical imaging using antibodies labeled with near infrared fluorophores is a sensitive imaging modality that might be used during surgery to assure complete removal of malignant tissue. We evaluated the feasibility of dual modality imaging and image guided surgery with the dual labeled anti-carbonic anhydrase IX antibody preparation (111)In-DTPA-G250-IRDye800CW in mice with intraperitoneal clear cell renal cell carcinoma. MATERIALS AND METHODS: BALB/c nu/nu mice with intraperitoneal SK-RC-52 lesions received 10 μg DTPA-G250-IRDye800CW labeled with 15 MBq (111)In or 10 μg of the dual labeled irrelevant control antibody NUH-82 (20 mice each)...
August 2015: Journal of Urology
Limin Zhang, Haowen Jiang, Gang Xu, Hui Wen, Bin Gu, Jun Liu, Shanghua Mao, Rong Na, Yan Jing, Qiang Ding, Yuanfang Zhang
In order to investigate the two members of the EF‑hand Ca2+ binding protein S100 family, S100A8 and S100A9, in renal cell carcinoma (RCC), serum samples were collected from patients with RCC, transitional cell carcinoma in the kidney, benign renal masses and normal controls. The samples were analyzed by isobaric tags for relative and absolute quantification technology to identify the differential expression of S100A8 and S100A9 in the respective groups. Hierarchical clustering analysis was then conducted for the samples and the relevant selected gene...
June 2015: Molecular Medicine Reports
Hao Lin, Jin-cheng Pan, Fa-ming Zhang, Bin Huang, Xu Chen, Jin-tao Zhuang, Hua Wang, Cheng-qiang Mo, Dao-hu Wang, Shao-peng Qiu
BACKGROUND: Vasculogenic mimicry (VM), a new pattern of tumor microcirculation system, has been proved to be important for tumor growth and progression and may be one of the causes of antiangiogenesis resistance. Matrix metalloproteinase-9 (MMP9) was shown to correlate with VM formation in some other cancers. However, the relationship between VM formation and MMP9 in renal cell carcinoma (RCC) has not been determined. METHODS: The VM formation and MMP9 expressions were analyzed by CD34/periodic acid-Schiff dual staining and immunohistochemistry in 119 RCC specimens...
April 2015: Urologic Oncology
Xu-Yong Lin, Heng Zhang, Na Tang, Xiu-Peng Zhang, Wei Zhang, En-Hua Wang, Yu-Chen Han
AIMS: High expression of carbonic anhydrase IX (CA IX) has been reported in clear cell renal cell carcinoma (ccRCC); few studies have reported CA IX expression in other tumours with predominantly clear cell morphology. The aim of study was to examine the expression and diagnostic implications of CA IX in these latter tumours. METHODS AND RESULTS: An immunohistochemical study was performed of 159 tumours with predominantly clear cell morphology. The results showed that, in addition to primary (25/25) and metastatic (10/11) ccRCC, CA IX was also expressed in breast (2/2), pulmonary (3/5) and hepatic (1/4) clear cell carcinoma, urothelial carcinoma with clear cell change (3/6), clear cell meningioma (4/6) and ependymoma (2/3), haemangioblastoma (10/10), and clear cell hidradenoma (5/6)...
April 2015: Histopathology
Sean R Williamson, Liang Cheng, John N Eble, Lawrence D True, Nilesh S Gupta, Mingsheng Wang, Shaobo Zhang, David J Grignon
Rare renal epithelial neoplasms have been recognized to have an angioleiomyoma or leiomyoma-like proliferation of stromal smooth muscle; however, the nature of these tumors and their relationships to other renal cell carcinomas are poorly understood. We analyzed 23 such tumors for their clinicopathological, immunohistochemical, and cytogenetic features using fluorescence in situ hybridization. Twelve showed a homogeneous combination of features and were reclassified as renal cell carcinoma with angioleiomyoma-like stroma...
February 2015: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Adelina Luong-Player, Haiyan Liu, Hanlin L Wang, Fan Lin
OBJECTIVES: To immunohistochemically evaluate the carbonic anhydrase IX (CA IX) expression on 1,551 cases of tumors and normal tissues from various organs. METHODS: Immunohistochemical evaluation of the expression of CA IX was performed on 1,125 malignant tumors, 69 benign neoplasms, and 322 normal tissues on tissue microarray sections and 18 intrahepatic cholangiocarcinomas (ICCs) and 17 hepatocellular carcinomas (HCCs) on routine sections. RESULTS: There was overexpression of CA IX in clear cell renal cell carcinoma (CRCC) (88%, 68/77)...
February 2014: American Journal of Clinical Pathology
Haijun Zhou, Shaojiang Zheng, Luan D Truong, Jae Y Ro, Alberto G Ayala, Steven S Shen
Clear cell papillary renal cell carcinoma (CCP-RCC) has recently been recognized as a distinct subtype of renal cell carcinoma (RCC) due to its unique morphologic, immunohistochemical, and genetic features and indolent clinical behavior. However, the incidence of this tumor in a nephrectomy series for renal mass has not been fully investigated. Twelve cases of CCP-RCC were identified from a total of 290 consecutive partial (n = 137) or radical nephrectomies (n = 153) for RCC from 2010 to 2012 in our hospital...
January 2014: Human Pathology
Brett Delahunt, John C Cheville, Guido Martignoni, Peter A Humphrey, Cristina Magi-Galluzzi, Jesse McKenney, Lars Egevad, Ferran Algaba, Holger Moch, David J Grignon, Rodolfo Montironi, John R Srigley
The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome...
October 2013: American Journal of Surgical Pathology
Michelle Pramick, Amy Ziober, Zhanyong Bing
Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described low-grade renal cell tumor. In this study, we investigated the expression of paired box 8 (PAX-8), carbonic anhydrase IX (CA IX), CK7, and α-methylacyl-CoA-racemase (AMACR) in this tumor by immunohistochemistry in a group of 20 cases of CCPRCC. Clear cell papillary renal cell carcinoma showed diffuse (70%) or intermediate (30%) nuclear positivity for PAX-8 in each case, with predominantly moderate intensity (50%). Ninety percent of the cases showed some degree of cytoplasmic staining for CA IX, predominantly with moderate intensity (50%)...
October 2013: Annals of Diagnostic Pathology
Constantijn H J Muselaers, Otto C Boerman, Egbert Oosterwijk, Johannes F Langenhuijsen, Wim J G Oyen, Peter F A Mulders
BACKGROUND: Improved and more frequent radiologic evaluation has resulted in increased identification of renal masses of unknown origin, which frequently pose a diagnostic dilemma for urologists. OBJECTIVE: Carbonic anhydrase IX (CAIX) is an antigen ubiquitously expressed in clear cell renal cell carcinoma (ccRCC). The specific and high level of expression in ccRCC makes CAIX an excellent target for imaging ccRCC lesions. We present our experience with immuno-single-photon emission computed tomography (immunoSPECT) imaging with the indium-111 ((111)In)-labeled anti-CAIX antibody girentuximab in patients presenting with either a primary renal tumor or a history of ccRCC and lesions suspect for metastases during follow-up...
June 2013: European Urology
Cor Hj Lamers, Stefan Sleijfer, Sabine van Steenbergen, Pascal van Elzakker, Brigitte van Krimpen, Corrien Groot, Arnold Vulto, Michael den Bakker, Egbert Oosterwijk, Reno Debets, Jan W Gratama
Autologous T cells genetically modified to express a chimeric antibody receptor (CAR) against carboxy-anhydrase-IX (CAIX) were administered to 12 patients with CAIX-expressing metastatic renal cell carcinoma (RCC). Patients were treated in three cohorts with a maximum of 10 infusions of a total of 0.2 to 2.1 × 10(9) CAR T cells. CTC grade 2-4 liver enzyme disturbances occurred at the lowest CAR T cell doses, necessitating cessation of treatment in four out of eight patients in cohorts 1 and 2. Examination of liver biopsies revealed CAIX expression on bile duct epithelium with infiltration of T cells, including CAR T cells...
April 2013: Molecular Therapy: the Journal of the American Society of Gene Therapy
Martina Takacova, Maria Bartosova, Lucia Skvarkova, Miriam Zatovicova, Ivana Vidlickova, Lucia Csaderova, Monika Barathova, Jan Breza, Peter Bujdak, Jaromir Pastorek, Jan Breza, Silvia Pastorekova
Carbonic anhydrase IX (CA IX) is regarded as one of the most prominent markers of tumor hypoxia with potential to serve as a diagnostic biomarker, prognostic indicator as well as tumor therapeutic target. The aim of the present study was to perform an in-depth analysis of CA IX expression in blood and tissue samples and to evaluate the significance of CA IX status for different renal cell carcinomas (RCCs). The expression of CA IX was determined in blood and tissue samples from 74 kidney cancer patients using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) and immunohistochemistry (IHC)...
January 2013: Oncology Letters
Toni K Choueiri, Suchun Cheng, Angela Q Qu, Jaromir Pastorek, Michael B Atkins, Sabina Signoretti
OBJECTIVE: Retrospective data analyses have suggested that carbonic anhydrase IX (CAIX) may have a predictive role in patients with metastatic clear cell renal cell carcinoma (ccRCC) receiving high dose interleukin-2 or sorafenib. We examined the predictive value of CAIX in estimating treatment outcome in patients receiving sorafenib vs. placebo as part of the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study. MATERIALS AND METHODS: Paraffin embedded tumor tissues were collected from 133 patients from the TARGET study (n = 903)...
November 2013: Urologic Oncology
Julien Edeline, Stéphanie Mottier, Cécile Vigneau, Florence Jouan, Christophe Perrin, Selim Zerrouki, Patricia Fergelot, Jean-Jacques Patard, Nathalie Rioux-Leclercq
Angiogenesis in clear cell renal cell carcinoma has received recent focus with the development of antiangiogenic therapies. Although tumor progression is known to be correlated with intratumoral and plasma levels of vascular endothelial growth factor-A, the role of tumor induced-angiogenesis remains unclear in these tumors. We analyzed the vascular network in a cohort of 73 clear cell renal cell carcinoma cases using endothelial immunostaining. We studied protein expression of vascular endothelial growth factor, Von Hippel Lindau, and carbonic anhydrase IX by immunohistochemistry, Von Hippel Lindau gene alteration by sequencing, deletion- and methylation-specific Multiplex Ligation-dependent Probe Amplification, and gene expression by pangenomic microarray and quantitative polymerase chain reaction in a subcohort of 39 clear cell renal cell carcinoma cases...
November 2012: Human Pathology
José M Giménez-Bachs, Antonio S Salinas-Sánchez, Leticia Serrano-Oviedo, Syong H Nam-Cha, Antonio Rubio-Del Campo, Ricardo Sánchez-Prieto
OBJECTIVE: This study aimed to evaluate the usefulness of carbonic anhydrase IX (CA-IX) expression in clear cell renal cell carcinoma (CCRCC) using two different techniques to detect protein expression. MATERIAL AND METHODS: An experimental, cross-sectional, analytical study was conducted to analyse proteins in renal tumour and healthy tissue specimens from 38 consecutive patients who underwent nephrectomy for renal cancer. CA-IX protein expression was measured by immunohistochemistry and Western blot analysis and quantified...
October 2012: Scandinavian Journal of Urology and Nephrology
B Walter, A Hartmann, F Hofstädter, K Junker, H Moch, S Bertz, S Denzinger, W Otto, M Gajda, C G Stoehr
To develop a reliable immunohistochemical marker panel differentiating between the three most common renal cell carcinoma (RCC) subtypes without inclusion of histomorphologic criteria we investigated protein expression of vimentin, glutathione S-transferase alpha (GST-α), CD10, CD117 (C-KIT), carbonic anhydrase 2 (CAII), parvalbumin, alpha-methyl-CoA-racemase (AMACR), and cytokeratin-19 (CK 19) in 65 age and stage matched trios of clear cell carcinoma, papillary renal carcinoma and chromophobe renal carcinoma using tissue microarrays...
March 2012: Virchows Archiv: An International Journal of Pathology
Daniel P Donato, Matthew T Johnson, Ximing J Yang, Debra L Zynger
AIMS: High expression of carbonic anhydrase IX (CAIX) is reported for clear cell renal cell carcinoma (RCC), with a paucity of data for non-renal genitourinary or adrenal tumours. This study investigated the immunohistochemical expression of CAIX throughout the genitourinary tract and adrenal gland. METHODS AND RESULTS: High expression in the renal cortex was restricted to clear cell, papillary and clear cell papillary RCC and carcinoid. Core biopsies of clear cell RCC were consistently positive...
December 2011: Histopathology
Stephen M Rohan, Yonghong Xiao, Yupu Liang, Maria E Dudas, Hikmat A Al-Ahmadie, Samson W Fine, Anuradha Gopalan, Victor E Reuter, Marc K Rosenblum, Paul Russo, Satish K Tickoo
Over the past few years several investigators have independently described unique low-grade renal epithelial neoplasms with clear cytoplasm, focal to diffuse papillary architecture, and occasional leiomyomatous stromal metaplasia that are not currently recognized in the World Health Organization classification of renal tumors. These tumors have been referred to by a variety of names including clear-cell papillary renal cell carcinoma and recently "clear-cell tubulopapillary renal cell carcinoma". On the basis of the available data, such tumors are positive for cytokeratin 7 (CK7) and carbonic anhydrase IX (CA9), while being negative for CD10, α-methylacyl-CoA racemase (AMACR), and TFE3...
September 2011: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
2015-05-07 09:05:29
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