Identification and Classification of Differentially Expressed Genes in Renal Cell Carcinoma by Expression Profiling on a Global Human 31,500-Element cDNA Array

Boer, Judith M.; Huber, Wolfgang; Sültmann, Holger; Wilmer, Friederike; Heydebreck, Anja von; Haas, Stefan A.; Korn, Bernhard; Gunawan, Bastian; Vente, Andreas; Füzesi, L.; Vingron, Martin; Poustka, Annemarie

doi:10.1101/gr.184501

Cited by 178 publications

(150 citation statements)

References 43 publications

(41 reference statements)

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“…Parvalbumin is a calcium-binding protein proposed recently as a useful marker to identify renal epithelial neoplasms with differentiation toward the distal nephron such as chromophobe renal cell carcinoma and oncocytoma. [13][14][15] In this study, we demonstrated that parvalbumin immunostained all 42 chromophobe renal cell carcinoma and used Western blot analysis to Endogenous biotin in kidney tissue and renal tumors can lead to confusing results. In this study, three different developing systems that are not sensitive to endogenous biotin were used to overcome this problem.…”

Section: Discussionmentioning

confidence: 99%

CD10 is expressed in a subset of chromophobe renal cell carcinomas

et al. 2004

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CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P ¼ 0.003) and mitotic figures (P ¼ 0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas. Keywords: chromophobe renal cell carcinoma; renal cell carcinoma; immunohistochemistry; CD10; parvalbumin The importance of distinguishing the different types of renal cell carcinoma is underscored by the fact that they have different prognoses. 1-3 CD10, a cell surface metalloproteinase localized to the proximal nephron of the normal adult kidney, 4 has been proposed as a useful tool in the differential diagnosis of renal epithelial neoplasms. [5][6][7] This molecule has been described as a positive immunohistochemical marker for the two most common types of kidney cancer, clear cell and papillary renal cell carcinomas. [5][6][7][8][9] Previous studies analyzing CD10 immunoreactivity in a total of 25 chromophobe renal cell carcinomas have found negative reactions, 5,7 whereas Holm-Nielsen et al 10 found CD10 expressed in all three chromophobe carcinomas studied and Higgins et al 11 found a positive reaction in one of three tumors tested. In this study we undertook to investigate CD10 and parvalbumin immunoreactivity in a large series of clear cell, papillary, and chromophobe renal cell carcinomas. Materials and methods Patients and Tissue SamplesWe studied the immunohistochemical expression of CD10 and parvalbumin in 75 clear cell renal cell carcinomas, 51 papillary renal cell carcinomas and 38 chromophobe renal cell carcinomas (including 36

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Section: Discussionmentioning

confidence: 99%

CD10 is expressed in a subset of chromophobe renal cell carcinomas

et al. 2004

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“…7,8 So far, most microarray studies on RCC metastasis comprise metastatic and nonmetastatic primary RCC. 9,10 Only a few studies include Mets of RCC to identify expression patterns associated with metastatic spread [11][12][13] since fresh-frozen metastatic lesions are rare because of their restricted surgical treatment. However, these studies have never addressed the particular characteristics of metastatic spread mentioned above.…”

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confidence: 99%

Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease‐free interval and the number of metastases per patient

Wuttig

Baier²,

Fuessel

et al. 2009

Intl Journal of Cancer

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Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI 9 months) and late (DFI 5 years) Mets, and Mets derived from patients with few ( 8) and multiple ( 16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies. ' UICC Key words: kidney cancer; lung metastases; oligonucleotide microarraysIn numerous tumour types, the development of metastases (Mets) causes the patients' death. The median survival of renal cell carcinoma (RCC) patients amounts to merely 6 to 12 months after Mets have been diagnosed. 1 RCC is the urological cancer with the highest percentage of tumour-related deaths 2 because metastasis occurs in about 60% of the patients. 3 The preferential localization of RCC Mets is the lung. 1 In contrast to the emerging development of molecular-based therapies for RCC in the last few years, 3 molecular prognostic markers are still missing. Despite the knowledge of several molecular factors involved in metastatic spread like angiogenesis, cell adhesion, invasion or migration, 4,5 little is known about specific characteristics of this complex process. These are, for example, primary-dependent site-specific metastasis, 6 varying dormancy periods of Mets originating from the same primary tumour entity causing disease-free intervals (DFI) ranging from several months to many years, or the differing number of Mets in patients with the same primary tumour. Knowing the molecular fundamentals of these phenomena would support the prognosis of patients' outcome and facilitate the decision for an appropriate therapy regime, particularly in RCC where the DFI and the number of Mets are important predictors of clinical...

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“…MUC18 and VCAM-1 adhesion molecules, LOX-1, laminin and collagen IV) are also overexpressed, suggesting that this feature may be involved in the progression of RCC. 2,27 The overexpression of several interferon-regulated genes (IIP-9-27, IFI-27, GBP2, MIG, IFI-16 and TAP-1) may explain the clinical benefit of IFN therapy in RCC.…”

Section: Studies On Genetic or Protein Profilesmentioning

confidence: 99%

“…A further development in the field may come from the data obtained from global genomic studies revealing gene signature of clear cell RCC containing several IFN-responsive genes. 2,27 The determination of the expression of IFN-responsive genes in the individual RCC, and analysis of the success of cytokine therapy may identify novel predictive markers for this type of therapy.…”

Section: Targeting Genes and Pathwaysmentioning

confidence: 99%