Expression of MUC1, Thomsen-Friedenreich-related antigens, and cytokeratin 19 in human renal cell carcinomas and tubular clear cell lesions

Cao, Yi; Karsten, Uwe; Zerban, Heide; Bannasch, Peter

doi:10.1007/pl00008210

Cited by 45 publications

(36 citation statements)

References 31 publications

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“…The immunoreactivity for MUC1 in the great majority of renal cell carcinomas in our series is in accordance with the results obtained in other studies, in which immunoreactivity with 'EMA' 27,[45][46][47] or 'MUC1' [3][4][5][6]28 antibodies was observed in 43-100% of renal cell carcinomas. These studies mainly dealt with conventional cancers.…”

Section: Discussionsupporting

confidence: 93%

“…26 Regarding renal cell carcinomas, MUC1 expression is common in conventional tumors and has been reported to be associated with tumor grade and stage. [3][4][5][6]27,28 Prognostic relevance, however, is still under debate, since some authors noticed a significant influence on patients' outcome, [3][4][5]27 whereas others failed to detect an influence on tumor aggressiveness in experimental systems. 29 The cadherins constitute a family of transmembrane glycoproteins that function as calcium-dependent homotypic adhesion molecules and are expressed by most epithelia.…”

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confidence: 99%

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Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases

et al. 2003

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MUC1 (epithelial membrane antigen) is a membrane-associated mucin known to interfere with both cell-cell and cell-matrix adhesions. Overexpression has been associated with poor prognosis in a variety of cancers. We investigated the expression of MUC1 (using two different antibodies, MA695 and E29) and E-cadherin in renal cell carcinomas (137 conventional, 23 chromophobe, 20 papillary, and eight unclassified tumors) with respect to diagnostic and prognostic significance using a tissue microarray technique. Immunoreactivity was correlated with histological subtype, pT-stage, and grade using the v 2 test or the Fisher's exact test, respectively. Impact on disease-free survival was analyzed using the Kaplan-Meier method and the log-rank test. Immunoreactivity of more than 10% of cancer cells with MA695, E 29, and E-cadherin antibodies was found in 112/133 (84%), 86/133 (65%), and 7/131 (5%) conventional, 20/22 (91%), 19/22 (86%), and 21/22 (95%) chromophobe, 13/20 (65%), 8/20 (40%), and 3/20 (15%) papillary as well as 5/8 (63%), 5/8 (63%), and 4/8 (50%) unclassified carcinomas, respectively. The two different MUC1 antibodies yielded comparable staining results. A diffuse cytoplasmic staining pattern for MUC1 was found exclusively in chromophobe carcinomas, whereas conventional and papillary subtypes showed predominantly membranous staining (Po0.0001). Regarding papillary carcinomas, MUC1 was predominantly associated with type 1 (P ¼ 0.0001), and E-cadherin with type 2 (P ¼ 0.049) tumors. The cellular staining pattern of MUC1 in conventional tumors was related to pT-stage (P ¼ 0.002) and tumor grade (P ¼ 0.001): Low-stage (pT1/pT2) and grade (G1/G2) tumors showed a predominantly apical membranous staining, high-stage (pT3a/pT3b) and grade (G3/G4) tumors a predominantly circumferential membranous staining (with or without additional diffuse cytoplasmic immunoreactivity), which, in the conventional subtype, was associated with poor prognosis (Po0.0001). In conclusion, MUC1 and E-cadherin are diagnostically and prognostically useful markers in renal tumor pathology, especially when cellular staining patterns are considered. Keywords: kidney; cancer; MUC1; EMA; E-cadherin; differential diagnosis; prognosisMucins are high-molecular-weight (4200 kDa) glycoproteins with oligosaccharides attached to an apomucin protein backbone (core peptide) by Oglycosidic linkage.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases

et al. 2003

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“…Immunohistochemistry shows expression of the cognate protein to be present in tubules extending through the entire thickness of the renal lobe (Figure 3) but most concentrated in the papillary tips. At high magnification, the antiserum to keratin 19 is seen to stain the principal cells but not the intercalated cells of the collecting ducts as previously reported (Cao et al, 2000). Our gene expression analysis confirms high-level expression of SPARC in the glomeruli (Web Figure 2).…”

Section: Immunohistochemistrysupporting

confidence: 88%

Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray

Higgins

Wang

Kambham

et al. 2004

MBoC

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The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied gene expression in dissected renal lobes of five adult human kidneys using cDNA microarrays representing ϳ30,000 different human genes. Total RNA was isolated from sections of the inner and outer cortex, inner and outer medulla, papillary tips, and renal pelvis and from glomeruli isolated by sieving. The results revealed unique and highly distinctive patterns of gene expression for glomeruli, cortex, medulla, papillary tips, and pelvic samples. Immunohistochemical staining using selected antisera confirmed differential expression of several cognate proteins and provided histological localization of expression within the nephron. The distinctive patterns of gene expression in discrete portions of the kidney may serve as a resource for further understanding of renal physiology and the molecular and cellular organization of the nephron. INTRODUCTIONThe kidney is a multifunctional organ with critical roles in selective elimination of soluble wastes, acid base, electrolyte, and hormonal homeostasis, and regulation of blood pressure and erythropoiesis. The nephron, the functional unit of the kidney, is a highly ordered structure, consisting of several distinct specialized cell types. An ultrafiltrate of the blood, formed in the glomerulus traverses the nephron, where essential solutes are selectively reabsorbed, whereas wastes are concentrated and excreted. The diverse functions of the kidney are divided in a stereotyped manner among the cells of the nephron and associated structures. The specialization of function along the nephron is reflected in the gross anatomy of the renal lobe. The cortex contains glomeruli, the juxtaglomerular apparatus, and the proximal and distal convoluted tubules, where the plasma ultrafiltrate is formed and the majority of its components are reabsorbed, and the medulla contains the loop of Henle and collecting ducts, where the ultrafiltrate is concentrated.The characteristic pattern of functional specialization of cells along the length of the normal nephron should be accompanied by corresponding regional variation in gene expression patterns. Gene expression profiles of each segment could provide insight into the proteins and systems involved in the function of each portion of the nephron. A comprehensive view of gene expression would therefore contribute to an understanding of normal renal physiology and its derangement in renal disease. To further explore the genetic programs that underlie the function of the nephron, we have analyzed the gene expression patterns in isolated normal glomeruli and in ...

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“…The expression of CK7 and CK19 in ccRCC subsets suggests that these ccRCCs may represent specific subtypes with potential origin from the collecting duct system or with neo-expression of these CKs. 20 Here we demonstrate significant associations between the expression of specific CKs, the cell adhesion protein E-cadherin and cytogenetic alterations. Two ccRCC subtypes defined by CK7 and CK19 expression were determined to be associated with genetic stability, a distinct molecular signature as determined by expression array profiling and a more indolent clinical course.…”

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confidence: 57%

Association of cytokeratin 7 and 19 expression with genomic stability and favorable prognosis in clear cell renal cell cancer

Mertz

Demichelis

Sboner

et al. 2008

Intl Journal of Cancer

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The purpose of our study was to demonstrate that distinct cytogenetic alterations in the most common subtype of renal cell cancer, clear cell renal cell carcinoma (ccRCC), are reflected in protein expression profiles. We performed conventional cytogenetics and immunohistochemical analysis for cytokeratins (CKs) on 126 ccRCCs. Protein expression was evaluated in situ using a semiautomated quantitative system. The results were validated using an independent cohort of 209 ccRCCs with long-term follow-up. Cytogenetic alterations were identified in 96 of 126 ccRCCs, most of them involving chromosome 3 through loss, deletion or translocation. Expression of CKs and E-cadherin in ccRCC was associated with lack of cytogenetic alterations and low nuclear grade. In the validation set, CK7 and CK19 protein expression was associated with better clinical outcome. At the multivariate level, the best model included metastatic status and CK19 expression. Expression microarray analysis on 21 primary ccRCCs and 14 ccRCC metastases identified genes significantly associated with CK7 and CK19 expressing ccRCCs. Two novel ccRCC biomarkers associated with the CK7 positive ccRCC phenotype, PMS2 and MT1-MMP (MMP14), were further validated. We conclude that the variability observed for CK expression in ccRCC can be explained by genetic heterogeneity. Distinct molecular subtypes of ccRCC with prognostic relevance were identified, and the CK7/CK19 expressing subtype is associated with better outcome.

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Expression of MUC1, Thomsen-Friedenreich-related antigens, and cytokeratin 19 in human renal cell carcinomas and tubular clear cell lesions

Cited by 45 publications

References 31 publications

Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases

Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases

Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray

Association of cytokeratin 7 and 19 expression with genomic stability and favorable prognosis in clear cell renal cell cancer

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