Histological Types Of Renal Cell Carcinoma Research Articles

The content of soluble forms of galectins -1, -3, -4, -7, -9 in patients with renal cell cancer of various morphological types

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.

Quantitative and qualitative evaluation of toxic metals and trace elements in the tissues of renal cell carcinoma compared with the adjacent non-cancerous and control kidney tissues.

Toxic metals and trace elements (TMTE) are linked to the development of several human cancers. Many reports have documented the association between some TMTE and renal cell carcinoma. In this work, we assessed the presence (qualitative) and evaluated the concentration (quantitative) of 22 TMTE in three groups of kidney tissue samples: renal cell carcinoma (RCC), adjacent non-cancerous, and control kidney tissues from cadavers. A total of 75 paired specimens of RCC and adjacent non-cancerous tissues were harvested immediately after radical nephrectomy and preserved in 10% diluted formalin solution. Twelve specimens, age- and sex-matched from the normal kidney tissue of the cadavers, who died from non-cancerous reasons, were collected and served as control. All tissue specimens were subjected to evaluation of TMTE concentration (22 elements in each specimen) by using the inductively coupled plasma optical emission spectrometry (ICP-OES) technique. The tumor, histopathology, stage, and grade were correlated with the concentration and types of TMTE. The results showed that the histological types of RCC were as follows: clear cell type in 35 (21.5%), chromophobe 22 (13.5%), papillary 7 (4.5%), oncocytoma 5 (3.1%), and unclassified 6 (3.7%). ICP-OES revealed that tumorous (RCC) tissues had a higher concentration of 9 TMTE (Ca, Cd, K, Mg, Mn, Na, Pb, S, and Sr) compared with both the adjacent non-cancerous and control tissue. The adjacent non-cancerous kidney tissues showed the highest concentration of Fe, K, and Na. The control of kidney tissues from cadavers had the highest level of Cu, Zn, Mo, and B compared with the cancerous and adjacent non-cancerous tissues. Female patients had higher concentrations of Zn and Cu in the non-cancerous tissues of their kidneys. Younger patients had a higher concentration of B in the adjacent non-cancerous, and higher Cu in the cancerous tissues. Cadmium concentration was highest in the chromophobe cell type of RCC compared with other subtypes. There was no correlation between the TMTE concentration and the pathological stage of RCC.

Clinical Scenarios in Chronic Kidney Disease: Kidneys' Structural Changes in End-Stage Renal Disease.

Acquired cystic kidney disease (ACKD) and renal cell carcinoma (RCC) are the most important manifestations of end-stage kidneys' structural changes. ACKD is caused by kidney damage or scarring and it is characterized by the presence of small, multiple cortical and medullary cysts filled with a fluid similar to preurine. ACKD prevalence varies according to predialysis and dialysis age and its pathogenesis is unknown, although it is stated that progressive destruction of renal tissue induces hypertrophy/compensatory hyperplasia of residual nephrons and may trigger the degenerative process. ACKD is almost asymptomatic, but it can lead to several complications (bleeding, rupture, infections, RCC). Ultrasound (US) is the first level imaging technique in ACKD, because of its sensitivity and reliability. The most serious complication of ACKD is RCC, which is stimulated by the same growth factors and proto-oncogenes that lead to the genesis of cysts. Two different histological types of RCC have been identified: (1) RCC associated with ACKD and (2) papillary renal clear cell carcinoma. Tumors in end-stage kidneys are mainly small, multifocal and bilateral, with a papillary structure and a low degree of malignancy. At US, RCC appears as a small inhomogeneous nodule (<3 cm), clearly outlined from the renal profile and hypoechoic if compared with sclerotic parenchyma. In some cases, tumor appears as a homogeneous and hyperechoic multifocal mass. The most specific US sign of a small tumor in end-stage kidney is the important arterial vascularization, in contrast with renal parenchymal vascular sclerosis.

Comparative Outcome of Computed Tomography-guided Percutaneous Radiofrequency Ablation, Partial Nephrectomy or Radical Nephrectomy in the Treatment of Stage T1 Renal Cell Carcinoma.

Renal cell carcinoma (RCC) accounts for 3% of all cancers in adults. The indications for Radiofrequency Ablation (RFA) for renal carcinomas include T1a (tumor 4 cm or less, limited to the kidney), elderly patients, renal impairment, comorbidities, poor surgical candidate, and multiple bilateral renal masses. We retrospectively reviewed medical records, specifically investigating the indications, complications and outcomes of RFA and nephrectomy for treatment of RCC in a tertiary medical center with a predominantly Hispanic patient population. Forty-nine patients with RCC were evaluated. Nine patients had RFA, 9 had partial nephrectomy and 31 had radical nephrectomy. All patients among the 3 groups had stage T1N0M0 RCC at diagnosis. Tumor recurrence was observed in 2 (22%) patients that had RFA, one (11%) patient that had partial nephrectomy and no patients that had radical nephrectomy. One patient had recurrence of the tumor at the opposite kidney pole from the initial RFA site 4 years later. This particular patient did not have any tumor recurrence at the site of the initial RFA. A second RFA was performed on the recurrent tumor with no recurrence upon subsequent follow up visits. The second patient had recurrence of the RCC on 1 year follow that was discovered to be sarcomatoid RCC, which is an aggressive type with a poor prognosis. Our results support the clinical utility of RFA in patients with stage T1 RCC who are poor surgical candidates or those with reduced renal function. The clinical utility of RFA as an equally effective approach when compared to partial nephrectomy in patients with stage T1 RCC that meet strict indications for the procedure. The treatment choice should be individualized and based on the characteristics of the renal tumor such as size, location and histological type of RCC. We conclude that RFA presents a safe treatment choice for patients with RCC if long term follow up is maintained.

Met in urological cancers.

Met is a tyrosine kinase receptor that is considered to be a proto-oncogene. The hepatocyte growth factor (HGF)-Met signaling system plays an important role in tumor growth, invasion, and metastasis in many types of malignancies. Furthermore, Met expression has been reported to be a useful predictive biomarker for disease progression and patient survival in these malignancies. Many studies have focused on the clinical significance and prognostic role of Met in urological cancers, including prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial cancer. Several preclinical studies and clinical trials are in progress. In this review, the current understanding of the pathological role of Met in cancer cell lines, its clinical significance in cancer tissues, and its predictive value in patients with urological cancers are summarized. In particular, Met-related malignant behavior in castration-resistant PCa and the different pathological roles Met plays in papillary RCC and other histological types of RCC are the subjects of focus. In addition, the pathological significance of phosphorylated Met in these cancers is shown. In recent years, Met has been recognized as a potential therapeutic target in various types of cancer; therapeutic strategies used by Met-targeted agents in urological cancers are summarized in this review.

Genome-Wide Promoter Methylome of Small Renal Masses

The majority of renal cell carcinoma (RCC) is now incidentally detected and presents as small renal masses (SRMs) defined as ≤4 cm in size. SRMs are heterogeneous comprising several histological types of RCC each with different biology and behavior, and benign tumors mainly oncocytoma. The varied prognosis of the different types of renal tumor has implications for management options. A key epigenetic alteration involved in the initiation and progression of cancer is aberrant methylation in the promoter region of a gene. The hypermethylation is associated with transcriptional repression and is an important mechanism of inactivation of tumor suppressor genes in neoplastic cells. We have determined the genome-wide promoter methylation profiles of 47 pT1a and 2 pT1b clear cell, papillary or chromophobe RCC, 25 benign renal oncocytoma ≤4 cm and 4 normal renal parenchyma specimens by Infinium HumanMethylation27 beadchip technology. We identify gene promoter hypermethylation signatures that distinguish clear cell and papillary from each other, from chromophobe and oncocytoma, and from normal renal cells. Pairwise comparisons revealed genes aberrantly hypermethylated in a tumor type but unmethylated in normal, and often unmethylated in the other renal tumor types. About 0.4% to 1.7% of genes comprised the promoter methylome in SRMs. The Infinium methylation score for representative genes was verified by gold standard technologies. The genes identified as differentially methylated implicate pathways involved in metabolism, tissue response to injury, epithelial to mesenchymal transition (EMT), signal transduction and G-protein coupled receptors (GPCRs), cancer, and stem cell regulation in the biology of RCC. Our findings contribute towards an improved understanding of the development of RCC, the different biology and behavior of histological types, and discovery of molecular subtypes. The differential methylation signatures may have utility in early detection and particularly differential diagnosis for prognostic stratification as well as identify novel gene and pathway targets for therapeutic intervention.

Abstract 12: Serum carbonic anhydrase IX (CAIX) as diagnostic biomarker in clear cell renal cell carcinoma (ccRCC) patients .

Abstract Clinicians face important pitfalls in the treatment of Renal cell carcinoma (RCC), such as absence of symptoms in early stages of the disease, its high metastatic potential and its resistance to conventional therapy. These facts emphasize the requirement of early diagnosis to optimize the chance of cure. ccRCC, the most common histological type of RCC, is considered a cell metabolic disease which develops from the activation of pseudohypoxic pathways. The transmembrane enzyme CAIX, involved in pH homeostasis and expressed in ccRCC tumors, is considered to be one of the best cellular biomarkers of hypoxia. Our aim was to study the role of serum CAIX as diagnostic biomarker of ccRCC, taking into account that serum contains a rich untapped source of disease-specific information. Employing a quantitative ELISA test (R&amp;D System), the expression of serum CAIX of 30 ccRCC patients and 16 healthy controls was evaluated. Samples from cancer patients were taken before surgery, without any previous treatment (S1), and after tumor removal (S2). ccRCC patients showed significantly elevated values of serum CAIX (Median 75.89 pg/ml, range 30,8-1482,9) respect to the levels observed in healthy controls (23.29, 0.0-79.9). On the basis of the optimal cut-off point of 34,821 pg/ml serum CAIX, 22/30 cancer patients showed high values of CAIX versus only 1/15 healthy controls (p&amp;lt; 0.01, Chi square test). The assay of serum CAIX expression in our population exhibited a sensitivity of 93.8% and a specificity of 73.3%. Besides, we demonstrated that Stage I ccRCC patients showed significantly lower levels of the circulating enzyme (Md, range expressed in pg/ml CAIX: Stage I= 45.3, 30.8-107.9 vs Stage IV=102.9, 36.2-1482.9; MW test p&amp;lt;0.001). Then, we analyzed whether already established clinicopathological variables in RCC were associated with serum CAIX levels, finding a remarkable correlation with tumor size (Spearman test p&amp;lt;0.01). Then, we investigated the usefulness of serum CAIX in the follow-up of these patients. Interestingly in 20/30 (66.7%) ccRCC patients values of CAIX decreased after tumor removal (S2 vs S1). We conclude that serum CAIX could be a useful diagnostic biomarker in ccRCC patients. This would be of relevant importance as there is a lack of molecular biomarkers for this pathology. Citation Format: Maria Elena Knott, Myriam Nuñez, Maria Natalia Gandur Quiroga, Gaston Boggio, Julieta Grasselli, Guillermo Gueglio, Pedro Rondot Radío, Mariano Brzesinski, Leonardo Pasik, Carla Pulero, Ana Alvarez, Hector Malagrino, Patricio Garcia Marchiñena, Alberto Jurado, Elisa Bal de Kier Joffe, Maria Guadalupe Pallotta, Lydia I. Puricelli. Serum carbonic anhydrase IX (CAIX) as diagnostic biomarker in clear cell renal cell carcinoma (ccRCC) patients . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 12. doi:10.1158/1538-7445.AM2013-12

Genetic Testing by Cancer Site

The roles of renal cell carcinoma (RCC) and urothelial cancers of the upper urinary tract are often overlooked as indicators for genetic risk assessment. The key features of 5 hereditary cancer susceptibility conditions involving an increased risk for RCC are discussed. von Hippel-Lindau disease, hereditary papillary RCC, and hereditary leiomyomatosis and RCC each predispose to a specific histological type of RCC, whereas Birt-Hogg-Dubé and hereditary paraganglioma/pheochromocytoma entail a variety of histologic findings. Familiarity with the rare or uncommon clinical features associated with these conditions, such as cutaneous neoplasms, paraganglioma/pheochromocytoma, and recurrent spontaneous pneumothoraces, aids in identifying patients with an underlying RCC susceptibility. A path to identifying syndromic cases lies in thorough investigation of the patient's medical history, their family history, and the histological type of RCC reported in the family. A guide to genetic predisposition testing for RCC is proposed. Upper urinary tract cancers in Lynch syndrome are also discussed.

Abstract 5570: Prognostic biomarkers in patients with clear cell renal cell carcinoma (ccRCC)

Abstract In Argentina the renal cell carcinoma (RCC) is the 9th cause of death for cancer in males and 13th in women. Clear cell RCC (ccRCC), the most common histological type of RCC, exhibits a wide spectrum of molecular characteristics that are closely associated with the deregulations of metabolic pathways involved in oxygen-, iron-, energy-, or nutrient-sensing. Primary ccRCC comprises a heterogeneous group of entities with variable clinical outcomes, so the understanding of their molecular features has critical importance to define individual metastatic risk. The aim of this study was to determine tumor tissue expression of specific molecules associated with angiogenic pathways triggered by hypoxic conditions (VEGFR1/Flk-1, VEGFR2/Flt-4 and PDGF-A receptor), with the glucose metabolism (Glut-1) or with survival pathways (p53). Antigen expressions were analyzed by immunohistochemistry on formalin fixed paraffin embedded ccRRC tumors [men: n=18, age: Md 55 years (range 46-72); women: n=12, age: 54.5 (49-82)], from patients who underwent a surgical resection as first treatment. The relationships between the expression of the different antigens and the known prognostic factors in ccRCC were analyzed by Chi-square. The Pearson test was used for correlation analysis. The Kaplan-Meier method was used to estimate disease-free survival (DFS). We observed that about 60-70% of ccRCC tumors expressed VEGFR1, VEGFR2 and Glut-1 at membrane level, but only 15% of them showed PDGF-A staining. In addition, 34% of samples expressed p53 at nuclear level. VEGFR1 expression correlated with the expression of the other membrane receptors studied (p&amp;lt;0.05 Pearson test). Interestingly VEGFR2 and PDGF-A immunopositivity on ccRCC tumors could be associated with the presence of metastasis at diagnosis (p&amp;lt;0.05, Chi square test). On the other hand, the expression of membrane VEGFR2 correlated with tumor size (p&amp;lt;0.01 Pearson). No association was observed between the expression of these biomarkers and histological grade, Fuhrman classification or clinical stage. Kaplan-Meier curves and Log rank test showed that no one of the tumor markers studied were associated with DFS; however we observed that those patients who never relapsed were negative for VEGFR2 and Glut1 antigens.In conclusion, we found that some of the studied biomarkers could be associated with some clinical parameters. In particular, VEGFR2 and PDGF-A membrane immunopositivity was associated with metastatic disease. However, the presence of these antigens in ccRCC samples obtained from surgery did not predict disease-free survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5570. doi:1538-7445.AM2012-5570

1802 SURGICAL OUTCOME AND PROGNOSTIC FACTOR FOR PT3B RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Advanced II1 Apr 20101802 SURGICAL OUTCOME AND PROGNOSTIC FACTOR FOR PT3B RENAL CELL CARCINOMA Jung Kwon Kim, Min Chul Cho, Yong Hyun Park, Seung Baik, Chang Wook Jeong, Ja Hyeon Ku, Cheol Kwak, and Hyeon Hoe Kim Jung Kwon KimJung Kwon Kim More articles by this author , Min Chul ChoMin Chul Cho More articles by this author , Yong Hyun ParkYong Hyun Park More articles by this author , Seung BaikSeung Baik More articles by this author , Chang Wook JeongChang Wook Jeong More articles by this author , Ja Hyeon KuJa Hyeon Ku More articles by this author , Cheol KwakCheol Kwak More articles by this author , and Hyeon Hoe KimHyeon Hoe Kim More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1726AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To analyze the surgical outcome and determine the prognostic factors influencing on survival in patients with pT3b renal cell carcinoma (RCC). METHODS From Feburary 1988 to April 2009, a total of 121 patients with pT3b RCC who underwent radical nephrectomy and thrombectomy were identified. Disease-specific survival (DSS) and overall survival (OS) rates were analyzed retrospectively according to various prognostic factors, including age, gender, body mass index (BMI), clinical symptoms, tumor side (Rt. vs. Lt.), tumor size, thrombus position (renal vein vs. IVC), invasion to perinephric fat or adrenal gland, lymph node involvement, distant metastasis at presentation, histological type of RCC, Fuhrmann nuclear grade, gross tumor necrosis, preoperative American Society of Anesthesiologists (ASA) score. RESULTS There are 84 men (69.4%) and 37 women (30.6%) whose mean age and mean follow-up duration was 56.6 years (range 26 to 78) and 37.3 months (range 1 to 211), respectively. The tumor was right-sided in 50 patients and left-sided in 71 patients. 78 patients (64.5%) presented with clinical symptoms, including palpable mass, gross hematuria, weight loss, flank pain. Of all patients, 96 had level I tumor thrombus, 19 had level II, and 6 had level III tumor thrombus. Of 54 patients who simultaneously received lymph node dissection, 5 had N1 disease and 13 had N2 disease. Histological types of RCC were conventional type in 85, chromophilic type in 7, chromophobic type in 5, collecting duct subtype in 2,unclassified type in 4 and unknown in 18. Sarcomatoid features were present in 9 patients. For Fuhrmann grade, grade 2 was present in 12 patients, 3 in 44, 4 in 23, unknown in 42, respectively. A total of 49 patients died. 5-year DSS and OS rate was 47% and 47%, respectively. On univariate analysis, BMI, presence of clinical symptom, pathological N stage, distant metastasis at presentation, tumor size, invasion to perinephric fat or adrenal gland, gross necrosis, sarcomatoid feature were associated with worse DSS and OS. On multivariate analysis, the presence of clinical symptom, distant metastasis at presentation, gross necrosis, pathological N stage was the independent prognostic factors for both DSS and OS. CONCLUSIONS Our data suggests that the presence of clinical symptom, distant metastasis at presentation, gross necrosis, pathological N stage was the independent prognostic factors for both disease-specific survival and overall survival rate in patients with pT3b RCC. Seoul, Republic of Korea© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e699 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jung Kwon Kim More articles by this author Min Chul Cho More articles by this author Yong Hyun Park More articles by this author Seung Baik More articles by this author Chang Wook Jeong More articles by this author Ja Hyeon Ku More articles by this author Cheol Kwak More articles by this author Hyeon Hoe Kim More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Lack of association between matrix metalloproteinase-1 (MMP-1) promoter polymorphism and risk of renal cell carcinoma

Investigate the possible association of insertion/deletion (2G/G) polymorphism at nucleotide -1607 of the MMP-1 promoter with the development and progression of renal cancer. In this study, we genotyped 217 individuals, 99 patients with renal cell carcinoma (RCC) and 118 controls without cancer. DNA specimens were extracted from epithelial buccal cells and paraffin-embedded tissue of RCC patients and from epithelial buccal cells and blood cells of healthy controls. The difference in frequency of 2G/2G genotype between controls (22.9%) and RCC patients (28.6%) was not statistically significant (p = 0.461). We also did not find correlation between 2G/2G and histological type of RCC. The comparison of genotype distribution and frequency of 2G allele in different populations showed a strong variability of 2G allele frequency among the different ethnic groups. This fact may influence on the collaboration of this 2G allele in RCC or others diseases. Our data suggest that the matrix metalloproteinase-1 (MMP-1) promoter polymorphism may not play a significant role in renal cell carcinoma patients in Brazil.

Expression of CD44 adhesion molecules in nonpapillary renal cell carcinoma and normal kidneys

Objectives. To analyze the relationship between the alterations in the expression of the CD44 gene in nonpapillary renal cell carcinoma (RCC) and several clinicopathologic factors. Methods. The expression of the CD44 gene in 10 human RCC cell lines, 60 nonpapillary RCC tumor samples, and 15 normal kidney samples was investigated by reverse-transcription polymerase chain reaction (RT-PCR) using a set of primers capable of amplifying all CD44 variant isoforms. The results were analyzed with respect to several clinicopathologic factors. Results. Nine of the 10 human RCC cell lines predominantly expressed the standard CD44 isoform (CD44s); CD44v10 was the major isoform in the 10th RCC cell line. The 15 normal kidney samples revealed the identical CD44 gene expression pattern; that is, CD44s, CD44v8-10, and CD44v10 were detectable in normal kidneys, and among them, CD44s was expressed most dominantly. In the 60 nonpapillary RCC samples, CD44s, CD44v8-10, and CD44v10 were the major isoforms in 46 (77%), 11 (18%), and 3 (5%) cases, respectively. Furthermore, the incidence of the predominant expression of CD44v8-10 in high-stage RCC was significantly higher than that in low-stage RCC. CD44s was more frequently expressed as a major isoform in clear cell RCC than in other histologic types of RCC. Conclusions. The results of this study show that the alternative splicing pattern of CD44 gene in RCC is different in each histologic type of RCC and suggest that CD44v8-10 upregulation in the progression of nonpapillary RCC is important.

EGF-r gene copy number changes in renal cell carcinoma detected by fluorescence in situ hybridization.

Expression of epidermal growth factor receptor (EGF-r) is a frequent event in renal cell carcinoma (RCC). To investigate the role of EGF-r gene copy number changes related to EGF-r overexpression, 50 RCC specimens were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry. Dual-labelling FISH with a repetitive pericentromeric probe for chromosome 7 and a probe for the EGF-r gene (at 7p13) was performed to analyse the EGF-r copy number in relation to chromosome 7 copy number on a cell-by-cell basis. Polysomy 7 was frequent in all histological types of RCC. Chromosome 7 polysomy was found in 26 of 35 clear cell (74 per cent), nine of nine papillary, and three of three chromophobe RCCs. EGF-r gene copy number was closely associated with the chromosome 7 copy number on a cell-by-cell basis. No EGF-r gene amplifications were found. EGF-r positivity was found in 37 of 50 cases (74 per cent) by immunohistochemistry. EGF-r positivity was more common in clear cell (81 per cent) than in papillary tumours (40 per cent; P = 0.029). Neither chromosome 7 nor EGF-r gene copy number was associated with EGF-r expression, indicating that an increased gene dosage is not a mechanism of EGF-r overexpression in RCC.

EGF‐r gene copy number changes in renal cell carcinoma detected by fluorescence in situ hybridization

Expression of epidermal growth factor receptor (EGF-r) is a frequent event in renal cell carcinoma (RCC). To investigate the role of EGF-r gene copy number changes related to EGF-r overexpression, 50 RCC specimens were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry. Dual-labelling FISH with a repetitive pericentromeric probe for chromosome 7 and a probe for the EGF-r gene (at 7p13) was performed to analyse the EGF-r copy number in relation to chromosome 7 copy number on a cell-by-cell basis. Polysomy 7 was frequent in all histological types of RCC. Chromosome 7 polysomy was found in 26 of 35 clear cell (74 per cent), nine of nine papillary, and three of three chromophobe RCCs. EGF-r gene copy number was closely associated with the chromosome 7 copy number on a cell-by-cell basis. No EGF-r gene amplifications were found. EGF-r positivity was found in 37 of 50 cases (74 per cent) by immunohistochemistry. EGF-r positivity was more common in clear cell (81 per cent) than in papillary tumours (40 per cent; P=0·029). Neither chromosome 7 nor EGF-r gene copy number was associated with EGF-r expression, indicating that an increased gene dosage is not a mechanism of EGF-r overexpression in RCC. © 1998 John Wiley & Sons, Ltd.