Genetic Subtyping of Renal Cell Carcinoma by Comparative Genomic Hybridization

Junker, Kerstin; Weirich, Gregor; Amin, Mahul B.; Morávek, P; Hindermann, Winfried; Schubert, Jöerg

doi:10.1007/978-3-642-59349-9_15

Cited by 50 publications

(33 citation statements)

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“…2,4 The significant difference in cancer-specific survival between patients with tumors and without 9p losses suggests that a tumor suppressor gene on 9p may be involved in tumor progression. [15][16][17][18] Loss of chromosome 9p was found in 12-36% of clear cell renal cell carcinomas by microsatellite analyses and comparative genomic hybridization. 19 demonstrated an association between loss of heterozygosity on chromosome 9p (24% of cases), using highly polymorphic microsatellite markers, and survival of patient for short duration.…”

Section: Discussionmentioning

confidence: 99%

Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma

et al. 2008

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Loss of chromosome 9p has been implicated in the progression of renal cell carcinoma. We evaluated the clinical utility of fluorescence in situ hybridization analysis of loss of chromosome 9p in 73 patients with clear cell renal cell carcinomas with varied stage, size, grade, necrosis (SSIGN) scores. Loss of chromosome 9p was observed in 13 tumors (18%). The 5-year cancer-specific survival of patients without loss of chromosome 9p was 88% and was 43% in those with loss of chromosome 9p (Po0.001). Local extension of the primary tumor according to the 2002 TNM staging system, lymph node involvement, the presence of distant metastases, and the SSIGN score were the other variables that predicted cancer-specific survival in univariate analysis. Loss of chromosome 9p was an independent prognostic factor in multivariate analysis. Our data indicate that the detection of chromosome 9p loss by fluorescence in situ hybridization analysis of clear cell renal cell carcinoma adds prognostic information beyond the pathological factors included in the current predictive models for renal cell carcinoma, such as SSIGN score.

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Section: Discussionmentioning

confidence: 99%

Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma

et al. 2008

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“…Junker et al (51) analyzed five cases of multifocal papillary renal tumors by comparative genomic hybridization and found at least one identical alteration in four of the five cases; however, this technique can only detect DNA copy number aberrations that span 2 to 10 Mb or more and, thus, is not ideal for clonality analysis. These results are also not surprising given the well-characterized and specific chromosomal copy number increases commonly seen in most cases of papillary renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Molecular Genetic Evidence for the Independent Origin of Multifocal Papillary Tumors in Patients with Papillary Renal Cell Carcinomas

Jones¹,

Eble²,

Wang³

et al. 2005

Clinical Cancer Research

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Purpose: In patients with papillary renal cell carcinoma, it is not uncommon to find two or more anatomically distinct and histologically similar tumors at radical nephrectomy.Whether these multiple papillary lesions result from intrarenal metastasis or arise independently is unknown. Previous studies have shown that multifocal clear cell renal cell carcinomas express identical allelic loss and shift patterns in the different tumors within the same kidney, consistent with a clonal origin. However, similar clonality assays for multifocal papillary renal cell neoplasia have not been done. Molecular analysis of microsatellite and chromosome alterations and X-chromosome inactivation status in separate tumors in the same patient can be used to study the genetic relationships among the coexisting multiple tumors. Experimental Design: We examined specimens from 21 patients who underwent radical nephrectomy for renal cell carcinoma. All patients had multiple separate papillary lesions (ranging from 2 to 5). Eighteen patients had multiple papillary renal cell carcinomas. Seven had one or more papillary renal cell carcinomas with coexisting papillary adenomas. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays were done for six microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p14 (D3S1285), 7q31 (D7S522), 9p21 (D9S171), 16q23 (D16S507), 17q21 (D17S1795), and 17p13 (TP53). X-chromosome inactivation analyses were done on the papillary kidney tumors from three female patients. Fluorescence in situ hybridization analysis was done on the tumors of selected patients showing allelic loss at loci on chromosome 7 and/or chromosome 17. Results:Twenty of 21 (95%) cases showed allelic loss in one or more of the papillary lesions in at least one of the six polymorphic markers analyzed. A concordant allelic loss pattern between each coexisting kidney tumor was seen in only 1of 21 (5%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the coexisting multiple papillary lesions was seen in two of three female patients. A discordant pattern of X-chromosome inactivation was seen in the tumors of the other female patient. Fluorescence in situ hybridization showed that the majority of tumors analyzed had gains of chromosomes 7 and 17. Two patients had one tumor with chromosomal gain and another separate tumor that did not. Conclusion: Our data suggest that, unlike multifocal clear cell renal cell carcinomas, the multiple tumors in patients with papillary renal cell carcinoma arise independently. Thus, intrarenal metastasis does not seem to play an important role in the spread of papillary renal cell carcinoma, a finding that has surgical, therapeutic, and prognostic implications.Approximately 10% to 15% of renal cell carcinomas are of the papillary type. Papillary renal cell carcinoma is more frequently multifocal than other types of renal cell carcinoma (1 -5).Papillary ad...

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“…Associations with outcome were evaluated for patients with clear cell RCC only given the documented differences in outcome and associations with outcome by RCC histological subtype. [9][10][11] …”

Section: Patient Selectionmentioning

confidence: 99%

“…8 In addition, previous studies have clustered chromophobe, papillary, and clear cell RCC subtypes into a single pathologic entity during analysis, despite the known histologic, genetic, and prognostic differences of these RCC subtypes. [9][10][11] Combined analysis of localized and metastatic RCC patients has further confounded the interpretation of prior studies analyzing the utility of preoperative laboratory values as indicators of prognosis. 8 Hence, to address these limitations, we examined a large cohort of patients with clinically confined (pNx/pN0, pM0), clear cell RCC and long-term follow-up to assess whether preoperative laboratory values might serve as independent prognosticators of outcome for patients with RCC.…”

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confidence: 99%

Association of Abnormal Preoperative Laboratory Values with Survival After Radical Nephrectomy for Clinically Confined Clear Cell Renal Cell Carcinoma

Magera

Leibovich

Lohse

et al. 2008

Urology

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Objectives-To determine whether preoperative laboratory values are independently associated with death from clinically confined clear cell renal cell carcinoma (RCC) after radical nephrectomy.Methods-We identified 1707 patients with clinically confined (pNx/pN0, pM0), unilateral, sporadic clear cell RCC treated with radical nephrectomy between 1970 and 2002. Associations of abnormal preoperative laboratory values including hypercalcemia, anemia, elevated erythrocyte sedimentation rate (ESR), and elevated alkaline phosphatase with death from RCC were evaluated using Cox proportional hazards regression models, both univariately and multivariately by adjusting for known prognostic features of the 2002 primary tumor classification, tumor size, nuclear grade, and coagulative tumor necrosis.Results-At last follow-up, 1009 patients had died, including 425 who died from RCC at a median of 3.0 years after surgery (range, 0 to 26 years). Even after adjusting for known prognostic features, 9% of patients with preoperative hypercalcemia exhibited significantly increased likelihood of dying from RCC compared with patients with normal or lower levels of serum calcium (relative ration [RR] 1.64; P = 0.002). Similarly, preoperative anemia (35% of patients; RR 1.27; P = 0.026) and elevated ESR (44% of patients; RR 1.66; P = 0.003) portended an increased risk of death from RCC even after multivariate adjustment.Conclusions-Abnormal preoperative laboratory values including hypercalcemia, anemia, and elevated ESR are independently associated with increased risk of cancer-specific death from clinically confined clear cell RCC. Consideration of these variables in future models may improve prognostic accuracy. We believe these factors should be routinely assessed and included in prospective studies of outcome in RCC patients.An estimated 36,000 patients will have been diagnosed with renal cell carcinoma (RCC) in 2005. 1 Despite surgical extirpation of clinically localized RCC, approximately 30% will have developed metastatic disease. 2 This high rate of disease progression has led many investigators to develop prognostic models for prediction of disease progression and cancer-specific death to aid in formulation of surveillance strategies and postoperative patient counseling. Various preoperative laboratory values, including anemia and elevated erythrocyte sedimentation rate (ESR), have been shown to be predictive of cancer-specific death and designated as prognostic markers by the Union Internationale Contre le Cancer (UICC) and American Joint Committee on Cancer (AJCC) consensus report. More specifically, most studies supporting the prognostic ability of preoperative laboratory values have been composed of small cohorts and not confirmed by larger contemporary series. In fact, one recent large retrospective study failed to reveal associations of hypercalcemia and anemia with cancer-specific death from RCC after multivariate analysis controlling for stage, grade, and ECOG performance status. 8 In addition, previous studies ...

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Genetic Subtyping of Renal Cell Carcinoma by Comparative Genomic Hybridization

Cited by 50 publications

References 6 publications

Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma

Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma

Molecular Genetic Evidence for the Independent Origin of Multifocal Papillary Tumors in Patients with Papillary Renal Cell Carcinomas

Association of Abnormal Preoperative Laboratory Values with Survival After Radical Nephrectomy for Clinically Confined Clear Cell Renal Cell Carcinoma

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