Adult Renal Cell Carcinoma Research Articles

Adult rhabdoid renal cell carcinoma.

Pediatric rhabdoid tumor of the kidney is regarded as a distinct neoplasm, whereas rhabdoid differentiation in adult renal cell carcinoma is usually found in association with conventional (clear cell) tumor, from which it is thought to evolve. To further characterize the rhabdoid phenotype in adult renal cell carcinoma and to determine its origin by genetic analysis. We performed histologic, immunophenotypic, and genetic analyses on 5 cases of adult renal cell carcinoma with rhabdoid differentiation, 3 samples of adjacent conventional (clear cell) tumor, and 6 conventional (clear cell) control tumors. Rhabdoid tumors differed from conventional (clear cell) carcinoma as follows: (1) macroscopically, rhabdoid tumors were solid white uniform masses; (2) microscopically, they had large rhabdoid cells with abundant eosinophilic cytoplasm, reduced lipid content, and the absence of a branching vascular pattern; and (3) biologically, they had a high metastatic potential. Despite these differences, loss of chromosome 3p in both the rhabdoid and clear cell carcinoma samples from 1 patient suggested a clonal origin. An identical mutation of the VHL gene in both rhabdoid and clear cell tumor samples from 2 patients confirmed a clonal origin for the histologically distinct tumor types in those cases. Adult rhabdoid renal cell carcinoma can in some cases arise from conventional (clear cell) renal carcinoma and should be considered a clinically important form of renal cell carcinoma separate from, but analogous to, sarcomatoid change.

Renal cell carcinoma with rhabdoid features: an aggressive neoplasm.

Only a few reports on renal cell carcinoma with rhabdoid features have been published. This study was performed to investigate the clinicopathological characteristics of renal cell carcinomas with rhabdoid features. Among 253 cases of renal cell carcinoma in adults, eight cases with rhabdoid features were detected. Rhabdoid areas ranged from 10% to 90% of each of the cases. Seven of the eight cases were TNM stage III or IV, and four of the eight cases died within 8 months of surgery. Immunohistochemically, the rhabdoid areas were positive for CAM 5.2 (4/8), AE1/AE3 (6/8), epithelial membrane antigen (6/8) and vimentin (8/8), and negative for myogenetic markers (0/8). The mean MIB-1 labelling index in the rhabdoid areas was higher than that in the definite carcinomatous areas. Ultrastructurally, perinuclear whorls of intermediate filaments were demonstrated in three of the eight cases using paraffin-embedded blocks. The rhabdoid areas in renal cell carcinoma have histological, immunohistochemical and ultrastructural similarities to malignant rhabdoid tumours. Renal cell carcinoma with rhabdoid features is a highly aggressive neoplasm and its malignant behaviour may be due to the high cell-proliferative activity of the rhabdoid areas. Rhabdoid features in renal cell carcinoma may represent the endpoint of clonal evolution of renal cell carcinoma (especially in clear cell type cases).

Frequent RASSF1A tumour suppressor gene promoter methylation in Wilms' tumour and colorectal cancer.

The 3p21.3 tumour suppressor gene (TSG) RASSF1A is inactivated predominantly by promoter methylation and rarely by somatic mutations. Recently we demonstrated that epigenetic inactivation of RASSF1A is frequent in both clear cell and papillary adult renal cell carcinomas (even though 3p21.3 allele loss is rare in papillary tumours). Wilms' tumour is the most common childhood kidney tumour, but relatively little is known about its molecular pathogenesis. Thus TSGs such as WT1, p16(CDKN2a) and p53 are inactivated in only a minority of cases. In view of the involvement of RASSF1A in adult renal cancers we investigated RASSF1A as a candidate Wilms' TSG. We detected RASSF1A hypermethylation in 21 of 39 (54%) primary Wilms' tumours. 3p21.3 allele loss was not detected in nine informative Wilms' tumours (five with RASSF1A methylation). In contrast to RASSF1A, only a minority (10.3%) of Wilms' tumours demonstrated p16 promoter methylation. As chromosome 3p allele loss is frequent in colorectal cancer, we proceeded to investigate RASSF1A promoter methylation in colorectal cancer and detected RASSF1A methylation in 80% (4/5) colorectal cancer cell lines and 45% (13/29) primary colorectal cancers. There was no correlation between RASSF1A and p16 methylation in colorectal cancer. We have demonstrated that RASSF1A inactivation is the most frequent genetic or epigenetic event yet reported in Wilms' tumourigenesis and that allelotyping studies may fail to identify regions containing important TSGs.

Expression of human mucin genes in normal kidney and renal cell carcinoma.

Human mucins are large O-glycoproteins expressed by epithelial cells. Mucins are thought to be implicated in cell protection, cell adhesion and signalling. The aim of this study was to investigate the expression of the human mucin genes (MUC1-4, 5AC, 5B, 6-7) in normal kidney and renal cell carcinoma. We analysed by in-situ hybridization, immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of these genes in normal adult kidney (n=14) and renal cell carcinomas (n=29). MUC1, MUC3 and MUC6 were expressed both in normal kidney and in renal carcinomas. In normal kidney, MUC1 was expressed in the distal convoluted tubules and in collecting ducts, whereas MUC3 was restricted to the proximal tubules. MUC4 was strongly expressed in epithelial urothelial cells of pyelocalyceal cavities. MUC6 was only detected by RT-PCR. In renal carcinoma, we showed a heterogeneous expression of MUC1 and MUC3 with an over-expression of MUC3 in renal clear cell carcinoma. The level of MUC3 expression by in-situ hybridization was associated with the nuclear grade in clear cell carcinoma. This study is the first large series investigating human mucin gene expression in the kidney. MUC1, MUC3 and MUC6 are expressed in normal and tumour kidney. The over-expression of MUC3 in renal cell carcinomas favours its implication in renal tumorigenesis.

Risk factors for adult renal cell carcinoma: a systematic review and implications for prevention

BJU InternationalVolume 88, Issue 7 p. 804-804 Risk factors for adult renal cell carcinoma: a systematic review and implications for prevention H. Kume, H. Kume Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this authorS. Takahashi, S. Takahashi Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this authorS. Teramoto, S. Teramoto Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this authorK. Isurugi, K. Isurugi Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this author H. Kume, H. Kume Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this authorS. Takahashi, S. Takahashi Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this authorS. Teramoto, S. Teramoto Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this authorK. Isurugi, K. Isurugi Division of Urology, Sanno Hospital, Tokyo, JapanSearch for more papers by this author First published: 07 July 2008 https://doi.org/10.1111/j.1464-410X.2001.2505b.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume88, Issue7November 2001Pages 804-804 RelatedInformation

Pax-2 expression in adult renal tumors

To assess the expression of the homeogene Pax-2 in adult renal cell carcinomas, we did a retrospective immunohistochemical analysis of 56 frozen tumor samples representing all major histologic subtypes of renal tumors. There were 33 conventional renal cell carcinomas (58.9%), 12 papillary renal cell carcinomas (21.4%), 4 chromophobe cell renal carcinomas, 4 urothelial cell renal carcinomas, and 3 oncocytomas. Forty-five tumors (62.5%) were localized, and 21 tumors had extrarenal involvement. Eight patients (14%) had metastatic disease at the end of the follow-up. We searched for relationships between Pax-2 expression and nuclear grading, TNM staging, Ki-67 proliferation index, expression of transforming growth factor-β1 (TGF-β1), an in vitro down-regulator of Pax-2 expression, and finally cytogenetic abnormalities. All histologic subtypes expressed Pax-2 protein, except urothelial renal carcinomas. The highest expression was in papillary renal cell carcinomas. In this subtype, all tumors and 83.3% ± 12.3% of tumor cells were immunoreactive for Pax-2. All but 2 conventional renal cell carcinomas expressed Pax-2, but with 26.3% ± 29.6% of immunoreactive cells (P <.001). Pax-2 expression was not correlated with nuclear grading (P =.6), tumor size (P =.3), and TGF-β1 expression (P =.1). Nevertheless, Pax-2 expression correlated with the Ki-67 proliferation index only for the conventional histologic subtype (P =.03). In this histologic subtype, Pax-2 expression was higher in patients with metastatic disease than in those without (P =.02). Pax-2 expression was not associated with specific cytogenetic abnormalities like trisomy 7 (P =.1), 3p deletion (P =.5), and hyperdiploidy (P =.2). TGF-β1 expression, positive in 33 tumors (59%), was not correlated with either Pax-2 expression (P =.1) or current prognostic factors such as nuclear grading (P =.2). Interestingly, we also observed an expression of TGF-βRI and TGF-βRII in the tumors with high nuclear grading (P =.005). We conclude that Pax-2 protein is expressed in all major histologic subtypes of renal cell carcinomas. The pattern of expression differs between these subtypes. Pax-2 expression in conventional renal cell carcinomas is correlated with the proliferation index and is significantly higher in patients with metastatic disease. HUM PATHOL 32:282-287. Copyright © 2001 by W.B. Saunders Company

Renal Cell Carcinoma With Rhabdoid Features

Neoplasms with rhabdoid features have been reported at many anatomic sites. In the kidney, rhabdoid tumors are typically found in children, whereas only rare examples have been reported in adults. Little is known of renal cell carcinomas (RCCs) that exhibit rhabdoid features. The objective of this study was to determine the incidence of RCC with rhabdoid attributes and characterize the histologic, immunophenotypic, and ultrastructural features by retrospective analysis of 480 consecutively identified cases of RCC in radical nephrectomy specimens. Immunohistochemical evaluation was performed in cases with rhabdoid foci using a panel of antibodies to pancytokeratin (pan-CK), CK7, CK20, epithelial membrane antigen (EMA), S-100 protein, desmin, vimentin, neuron-specific enolase (NSE), muscle-specific actin (MSA), smooth muscle actin (SMA), human melanoma, black-45 (HMB-45), and glial fibrillary acidic protein (GFAP). Electron microscopy was also performed in selected cases. The presence and extent of rhabdoid foci in relation to pathologic stage and grade were assessed. Twenty-three of 480 cases of RCC (4.7%) exhibited rhabdoid features. The 23 patients were all adults with a mean age of 61.8 years (age range, 33-84 yrs). Fifteen of the patients were men and eight were women. Histologically, the rhabdoid foci were typified by sheets and clusters of variably cohesive, large epithelioid cells with vesicular and often eccentric nuclei, prominent nucleoli, and large, paranuclear intracytoplasmic hyaline globules (inclusions). The presence of these rhabdoid features was related to high histologic Fuhrman grade of the nonrhabdoid carcinoma component, with an incidence of 0 of 84 grade I cases, eight of 300 grade 2 cases (2.6%), six of 70 grade 3 cases (8.9%), and nine of 26 grade 4 cases (34.6%; p = 3 x 10(-9)). The rhabdoid foci were all high grade. The presence of rhabdoid foci was also found in higher stage carcinomas. A total of 52% (12 of 23) of RCC cases with rhabdoid features exhibited extrarenal extension compared with 28% (24 of 92) of contemporary RCCs without rhabdoid features (p = 0.03). The size of the rhabdoid component ranged from 1 mm to more than 2 cm and comprised 1% to 50% of the renal mass. Immunoreactivity for vimentin (100%), NSE (79%), and panCK (56%) was present in the majority of cases. Substantial percentages of cases were immunopositive for EMA (47%) and S-100 protein (37%), with minimal to no immunohistochemical reactivity for CK7 (5%), SMA (5%), CK20 (0%), desmin (0%), MSA (0%), HMB-45 (0%), and GFAP (O%). A distinctive globular, paranuclear reaction pattern was found for the cytokeratin, EMA, and vimentin immunostains. Ultrastructurally, the rhabdoid cells had paranuclear intermediate filament aggregates or paranuclear condensation of organelles, often associated with peripheral vacuolization. Adult RCCs may harbor a rhabdoid component, and these neoplasms can be regarded as "composite" tumors. Rhabdoid elements are important to identify because of their high-grade nature, and association with high stage. Adult RCC with rhabdoid elements should be distinguished from pure rhabdoid tumors of kidney, in light of their clinicopathologic differences. Rhabdoid differentiation in adult renal cell carcinoma may represent clonal divergence and/ or evolution, and emergence of a particularly aggressive element.

Risk factors for adult renal cell carcinoma: a systematic review and implications for prevention.

BJU InternationalVolume 86, Issue 1 p. 20-27 Risk factors for adult renal cell carcinoma: a systematic review and implications for prevention R. Dhôte, R. Dhôte Service de Santé Publique, Service de Médecine Interne, andSearch for more papers by this authorM. Pellicer-coeuret, M. Pellicer-coeuret Service de Santé Publique,Search for more papers by this authorN. Thiounn, N. Thiounn Service d’Urologie, Université René Descartes, CHU Cochin Port-Royal, Saint-Jacques, Paris, FranceSearch for more papers by this authorB. Debré, B. Debré Service d’Urologie, Université René Descartes, CHU Cochin Port-Royal, Saint-Jacques, Paris, FranceSearch for more papers by this authorG. Vidal-trecan, G. Vidal-trecan Service de Santé Publique,Search for more papers by this author R. Dhôte, R. Dhôte Service de Santé Publique, Service de Médecine Interne, andSearch for more papers by this authorM. Pellicer-coeuret, M. Pellicer-coeuret Service de Santé Publique,Search for more papers by this authorN. Thiounn, N. Thiounn Service d’Urologie, Université René Descartes, CHU Cochin Port-Royal, Saint-Jacques, Paris, FranceSearch for more papers by this authorB. Debré, B. Debré Service d’Urologie, Université René Descartes, CHU Cochin Port-Royal, Saint-Jacques, Paris, FranceSearch for more papers by this authorG. Vidal-trecan, G. Vidal-trecan Service de Santé Publique,Search for more papers by this author First published: 25 June 2007 https://doi.org/10.1046/j.1464-410x.2000.00708.xCitations: 83 Dr Robin Dhôte, Service de Médecine Interne, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. E-mail: robin.dhote@cch.ap-hop-paris.fr Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume86, Issue1July 2000Pages 20-27 RelatedInformation

Glomerular TGF‐β1 expression in children with nephrotic syndrome

Summary: Transforming growth factor‐β (TGF‐β) has been suggested to contribute to the onset and/or progression of glomerulonephritis. However, data of TGF‐β in connection with the pathogenesis of nephrotic syndrome are still insufficient. an immunohistochemical study on the glomerular TGF‐β1 in nephrotic syndrome was carried out in order to clarify the pathological role of this substance. Ten cases of nephrotic syndrome were subdivided histologically into two groups: (i) six cases of minor glomerular abnormality (group M); and (ii) four cases of focal glomerular sclerosis (group F). Two cases with normal glomeruli, one case of normal portion of adult renal cell carcinoma, one case of normal portion of Wilm's tumour were also studied as controls. Four cases of asymptomatic haematuria (group H) and four cases of chronic non‐IgA glomerulonephritis syndrome (group C) were chosen compared to the nephrotic syndrome. Staining was evaluated semiquantitatively by light microscopy and by measuring the staining ratio compared to the glomerular area on an image analyzer. Both methods showed significantly larger staining in the glomeruli of group F, compared to group M. We concluded that TGF‐β1 plays an important role in the progression of nephrotic syndrome.

The Role of Radiotherapy for Adult Renal Cell Carcinoma

In this paper the most important articles about the role of radiotherapy for renal cell carcinoma (CPR) are reviewed. Both pre- and post-operative radiotherapy do not seem to improve the survival rates, nor perhaps the local control in comparison with surgery. But trials have been limited and with evident bias: patients were staged without stratification for prognostic factors (grading and lymphonode metastases in particular) and radiotherapy techniques were often incorrect because of too frequent early and late damage. The role of radiotherapy for treating the metastatic disease is undisputed Particularly for patients with a single metastasis, because of the possibility of long survival if adequately controlled.

Differentiation dependent expression of P-glycoprotein in the normal and neoplastic human kidney.

Adult renal cell carcinoma (RCC) is clinically resistant to chemotherapy. However, in nephroblastoma (NBL) chemotherapy has increased survival dramatically. We studied the P-glycoprotein (P-gp) expression of 18 RCC and 9 NBL as well as 1 benign renal adenoma and fetal renal tissue using three different monoclonal antibodies (MRK-16, C-219, JSB-1). P-gp was found positive with all three antibodies in 12/18 RCC, while only 2 tumors were completely negative. Staining varied with respect to intensity and number of positive cells [5%-90%]. Intense staining was seen at the apical side of malignant tubules in well differentiated parts of RCC and in tubular structures of the benign renal adenoma. Poorly differentiated parts of the tumors showed less staining. In NBL blastemal parts were negative. In 4/8 specimens showing focal epithelial differentiation, however, the luminal side of more differentiated tubular structures did stain, strongly resembling P-gp staining in the developing fetal human kidney. These results indicate that P-gp expression in normal (fetal) human kidney as well as in benign and malignant tumors derived from this organ depends on the degree of differentiation of tubules, which may have implications for chemotherapy sensitivity in both malignant tumors.

Expression of intermediate-sized filaments in developing and adult human kidney and in renal cell carcinoma.

We studied the distribution of intermediate-sized filaments in developing and adult kidneys and renal cell carcinoma (RCC) by indirect immunohistochemistry, using a pan-cytokeratin mouse monoclonal antibody (MAb), chain-specific anti-cytokeratin MAb, and anti-vimentin and anti-desmin MAb, to resolve controversy concerning intermediate-sized filament expression in the kidney. With the pan-cytokeratin MAb, cytokeratin expression was detectable in all stages of nephron development, starting with expression in the renal vesicles, the progenitors of the glomeruli, proximal tubules, Henle's loop, and part of the distal tubules. Using chain-specific anti-cytokeratin MAb, cytokeratin 8 and 18 expression was demonstrated in all developmental structures of the nephron, whereas cytokeratin 19 expression was more complex. None of the nephrogenic blastema cells from which the renal vesicles arise expressed cytokeratins. Transient expression of vimentin and cytokeratin 19 was observed in differentiating collecting ducts and proximal tubule cells at the S-shaped stage of nephron development, respectively. In RCC, cytokeratin expression closely resembled that of the mature proximal tubule, i.e., RCC cells expressed cytokeratins 8 and 18. However, in a subset of RCC additional cytokeratin 19 expression was noted. In addition, all except one RCC showed co-expression of cytokeratins and vimentin.

Phase II Trial of Methyl-gagand Melphalan in Metastatic Adult Renal Cell Carcinoma

A trial of melphalan and methyl-gag was undertaken in 16 patients with metastatic renal cell carcinoma. Among 14 evaluable patients, 6 had stabilization of disease. No significant responses were observed. While both drugs have produced occasional responses in renal cancer, their combination shows no therapeutic advantage.

Phase II Trial with High-Dose Elliptinium Acetate in Metastatic Renal Cell Carcinoma

Sixteen patients with adult metastatic renal cell carcinoma were treated with elliptinium acetate, 80 mg/m2.day, for 3 consecutive days every 3 weeks. Among the 14 patients evaluable, no objective effects were observed. The toxicity was mild and no patients experienced intravascular hemolysis.

Role of Natural Killer Activity in Development of Spontaneous Metastases in Murine Renal Cancer

We have studied the role of natural killer activity during the growth and dissemination of a transplantable renal adenocarcinoma (Renca) of spontaneous origin in BALB/c mice. The pattern of growth of this tumor accurately mimics that of adult human renal cell carcinoma in terms of clinical stages I–IV, particularly with regard to spontaneous metastasis to lung and liver. Renca is moderately sensitive to lysis by natural killer cells from normal mice and is more efficiently lysed by natural killer cells from mice treated with the biological response modifier maleic anhydride divinyl ether, a pyran copolymer. Our studies demonstrate that selective depression of natural killer activity by administration of antiserum specific for the neutral glycosphingolipid asialo GM1 correlated with increased formation of spontaneous metastases in the lungs, liver, and lymph nodes. Conversely, augmentation of natural killer activity by the biological response modifier decreased the formation of spontaneous metastases in lungs, liver and lymph nodes.Further, the suppression of natural killer activity and subsequent increased formation of metastases were accompanied by a significantly reduced survival time, whereas the augmented natural killer activity and decreased incidence of metastases in biological response modifier-treated mice were accompanied by an increase in time of survival. These results demonstrate a significant role for natural killer cells in the control of spontaneous metastasis during growth of this murine renal cancer.

Human chromophobe cell renal carcinoma.

Twelve renal cell carcinomas composed of "chromophobe" cells are described. This is the first report of renal chromophobe cell tumors in humans neoplasms of this cell type having been described previously only in experimentally induced adenomas in animals. By light microscopy chromophobe cells have slightly opaque or finely reticular cytoplasm when stained with haematoxylin and eosin. They may be distinguished from the clear cells of hypernephroid renal cell carcinomas by the strongly positive reaction of their cytoplasm with Hale's (1946) colloidal iron method and the weaker positive reaction with alcian blue. Vesicular structures, often containing internal vesicles, and possibly derived from the endoplasmic reticulum or from mitochondria are visible electronmicroscopically. Glycogen is present to a variable but slight extent so that it is usually detected only by electron microscopy. The twelve renal cell carcinomas described were composed entirely of chromophobe cells. They were derived from a series of more than 500 adult renal cell carcinomas giving a frequency of approximately 2%. To avoid confusion the descriptive term "light cell" should be discarded and replaced by either "clear cell" or "chromophobe cell" as appropriate, since it is assumed that chromophobe cell tumors have a different derivation from clear cell and other renal cell carcinomas. They may also have a different prognosis although this has not yet been established.

Roentgenologic triad of congenital multicystic kidney.

Congenital multicystic kidney is the most common cause of an abdominal mass in infancy. The disease may persist into the adult life and be incidentally discovered. Although it became a distinct pathologic entity in 1955, clinical and roentgenologic diagnosis of a congenital multicystic kidney could not be made with certainty. This is because the diagnostic features consisting of a unilateral nonfunctioning kidney with or without a palpable flank mass are also observed in Wilms’ tumor in children and renal cell carcinoma in adults, congenital unilateral hydronephrosis, renal vein thrombosis, renal artery occlusion, renal xanthogranulomatous pyelonephritis and renal agenesis. In view of lack of a diagnostic procedure to make an accurate diagnosis, these patients have been subjected to surgical exploration to confirm the clinical suspicion of congenital multicystic kidney, so as to make certain that one is not dealing with the more serious or malignant renal diseases considered in the differential diagnosis....