Prognostic significance of CA 125, CD44, and epithelial membrane antigen in renal cell carcinoma

Bamias, Aristotle; Chorti, Maria; Deliveliotis, Ch.; Τράκας, Νικόλαος; Skolarikos, Andreas; Protogerou, B.; Legaki, Stella; Tsakalou, Georgia; Tamvakis, N.; Dimopoulos, Meletios Α.

doi:10.1016/s0090-4295(03)00264-4

Cited by 30 publications

(26 citation statements)

References 22 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%

“…[3][4][5][6]27 These results are based on different criteria for evaluation of immunoreactivity, since some authors restricted themselves to a semiquantitative assessment, 4,27 whereas others also considered staining patterns. 3,5,6 With respect to semiquantitative analysis of MUC1 immunoreactivity, we were unable to reproduce the associations with pT-stage and grade.…”

Section: Discussionmentioning

confidence: 99%

“…For comparative analysis, specimens showing positive immunostaining in more than 10% of tumor cells were considered positive in accordance with previous studies. 4,27 In addition to the semiquantitative evaluation, staining patterns for MUC1 were classified as either (predominantly) membranous or (predominantly) diffuse. In a further step, the membranous pattern was further subdivided into a predominantly apical or a predominantly circumferential immunoreactivity (with or without an additional diffuse cytoplasmic immunoreactivity).…”

Section: Immunohistochemical Evaluation and Controlsmentioning

confidence: 99%

“…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. 2004

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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%

Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemical Evaluation and Controlsmentioning

confidence: 99%

mentioning

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. 2004

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“…Intriguingly, both negative regulators have been previously linked to tumorigenesis. M17S2 is a surface marker in ovarian cancer (25), and the expression of M17S2 was found to be inversely correlated to the survival in renal cell carcinoma patients (26). Cathepsin B is a lysosomal cysteine protease, and the overexpression of cathepsin B has been associated with ovarian cancer, adenocarcinoma, and other tumors (27).…”

Section: Resultsmentioning

confidence: 99%

Identification of p53 regulators by genome-wide functional analysis

Huang

Raya

DeJesus

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

142

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The p53 tumor-suppressor protein is a critical mediator of cellular growth arrest and the induction of apoptosis. To identify proteins involved in the modulation of p53 transcriptional activity, a gainof-function cellular screen was carried out with an arrayed matrix of Ϸ20,000 cDNAs. Nine genes previously unknown to be involved in regulating p53 activity were identified. Overexpression of seven of these genes (Hey1, Hes1, TFAP4, Osr1, NR2F2, SFRS10, and FLJ11339) resulted in up-regulation of p53 activity; overexpression of two genes (M17S2 and cathepsin B) resulted in down-regulation of p53 activity in mammalian cells. HES1, HEY1, and TFAP4, which are members of the basic helix-loop-helix transcription family, and OSR1 were shown to activate p53 through repression of HDM2 transcription. Ectopic expression of these basic helix-loop-helix transcription factors in both zebrafish and avian developmental systems activated p53 and induced apoptosis in vivo, resulting in a phenotype similar to that of p53 overexpression. Furthermore, ras-and myc-mediated transformation of mouse embryonic fibroblasts was abrogated by expression of HEY1 in a p53-dependent manner. These results suggest that these transcription factors are members of an evolutionarily conserved network that governs p53 function.

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