Papillary Renal Cell Tumors Research Articles

Mutation of the p53 tumour suppressor gene occurs preferentially in the chromophobe type of renal cell tumour.

Genomic DNA from 30 non-papillary and 20 chromophobe renal cell carcinomas (RCCs), 30 papillary renal cell tumours, and 20 renal oncocytomas was screened for the presence of mutations in exons 5-8 of the p53 tumour suppressor gene by polymerase chain reaction-single strand conformation polymorphism analysis and direct DNA sequencing. Mutations leading to an amino acid change were found only in 6 out 20 chromophobe RCCs. Microsatellite analysis of chromophobe RCCs revealed the loss of one allele at chromosome 17p in 14 out of 18 informative cases. No mutation of the p53 gene was found in five sarcomatous RCCs or in seven tumours of stage IV. This study shows that mutation of the p53 tumour suppressor gene does not correlate with the specific loss of DNA sequences at chromosome 17 in chromophobe RCCs, nor can it be used as a prognostic parameter for RCCs in general.

Mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinomas.

To define the possible role of the VHL gene in the development of sporadic renal cell carcinomas, 91 different parenchymal tumours of the kidney have been investigated for mutation of the VHL gene by single strand conformation polymorphism (SSCP) and/or heteroduplex (HD) techniques. Chromosome 3p deletion was detected in 98 per cent of non-papillary renal cell carcinomas and in 25 per cent of chromophobe renal cell carcinomas. In 22 of the 43 non-papillary renal cell carcinomas, abnormally migrating DNA bands were detected by SSCP and/or HD analysis. No mobility shift was seen in any of the 23 chromophobe renal cell carcinomas. In addition, 15 papillary renal cell tumours and ten renal oncocytomas, which are characterized by genetic changes other than loss of chromosome 3p sequences, were analysed for mutation of the VHL gene. None of these tumours showed abnormal migration patterns. The results indicate that mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinoma.

Molecular genetics of human renal cell tumours.

This review discusses the impact of molecular genetics on the diagnosis and prognosis of renal cell tumours as well as the genetic changes in renal cell tumours associated with von Hippel-Lindau disease and end-stage kidney disease. The use of molecular techniques enables the division of renal cell tumours into genetically and biologically well defined entities. The new classification system distinguishes between papillary renal cell tumours, including papillary renal cell adenoma and papillary renal cell carcinoma, nonpapillary renal cell carcinoma, chromophobe renal cell carcinoma and renal oncocytoma. The advantage of the new classification system is that genetic markers, in contrast to the tumour phenotype, are constant during tumour progression and allow a precise diagnosis even from a small biopsy specimen.

Cytogenetic characterization of a familial papillary renal cell carcinoma

We describe the first case of a familial renal cell carcinoma cytogenetically characterized as a papillary renal cell carcinoma. Cytogenetic and molecular studies were performed on primary renal cell carcinomas and normal kidney tissue from two members of the same family. Both patients showed a normal constitutional karyotype. The two tumors analyzed from the first patient showed the numerical chromosome alterations characteristic of papillary renal cell carcinomas. From the four tumors analyzed in the second patient, three of them presented the cytogenetic pattern of papillary renal cell tumors, and the fourth showed only structural chromosome abnormalities with the presence of a del(7)t(7;7) or dup(7) in all metaphases analyzed. Chromosome 3 was cytogenetically unaffected in all tumors from both patients, and restriction fragment length polymorphism analysis performed with probe pEFD145 (3p21.1–p23) did not detect any loss of heterozygosity.

High frequency of papillary renal-cell tumours in end-stage kidneys—is there a molecular genetic explanation?

High frequency of papillary renal-cell tumours in end-stage kidneys—is there a molecular genetic explanation?

Development of papillary renal cell tumours is associated with loss of Y‐chromosome‐specific DNA sequences

Twenty-two papillary renal cell tumours were analysed by Southern hybridization using eight DNA probes from homologous regions of the X and Y chromosomes and two Y-chromosome-specific DNA probes. Sixteen of the 19 papillary renal cell tumours of male patients showed the loss of Y-chromosome-specific sequences. No loss of heterozygosity was detected in three tumours that developed in females. The frequency of loss of the Y chromosome was established in 50 non-papillary renal cell carcinomas as well. Only seven of the 31 non-papillary renal cell carcinomas obtained from male patients had lost the Y-chromosome-specific sequences, whereas no allelic loss was found in 19 non-papillary tumours obtained from female patients. Papillary renal cell tumours show a strong male preponderance (6:1) and loss of Y chromosome in 84 per cent of the cases, whereas non-papillary renal cell carcinomas show only a slight male preponderance (1.5:1) and the Y chromosome is lost in only 22 per cent of the cases. These data suggest that a tumour suppressor gene is localized at one of the homologous regions of the X and Y chromosomes, the homozygous inactivation of which is associated with the development of papillary renal cell tumours.

The value of molecular genetic analysis in the diagnosis and prognosis of renal cell tumours.

Renal cell tumours have a heterogeneous morphology, which may also be changed during tumour progression. Through the use of molecular cytogenetic techniques, it has become possible to divide renal cell tumours into genetically well-defined entities. Papillary renal cell tumours are characterized by loss of the Y chromosome and trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20. Non-papillary renal cell carcinomas show a specific loss of chromosome 3p and trisomy of chromosome 5q sequences and frequent loss of chromosome 6q, 8p, 9 and 14q sequences. Chromophobe renal cell carcinomas are marked by a highly specific combination of loss of chromosomes 1, 2, 6, 10, 13, 17 and 21 and gross rearrangement of mitochondrial DNA. Subsets of renal oncocytomas show minimal karyotype alterations or translocation 11q13;? or loss of the Y chromosome and chromosome 1. There are some data suggesting that molecular genetic markers may be used not only for diagnosing of renal cell tumours but also for predicting the prognosis of tumour subtypes. Trisomy of chromosomes 7 and 17 and loss of the Y chromosome marks papillary renal cell adenomas, whereas additional trisomies such as those of chromosomes 3q, 8, 12, 16 and 20 are associated with papillary renal cell carcinomas. Although non-papillary renal cell tumours develop as a carcinoma, their clinical behaviour is in strong correlation with secondary karyotype changes such as loss of chromosomes 6q, 8p, 9 and 14q.

Renal cell carcinoma in dialysis patients.

Histopathological studies were performed in 18 dialysis patients with renal cell carcinoma. All patients were classified as stage I according to the criteria in the protocol of Robson. The 2 main cell types in these patients were granular (50%) and clear (44%) cell tumors. Thirty-nine percent of the carcinomas exhibited a predominantly acinar growth pattern, 27% had a papillary, and 17% exhibited a cystic growth pattern. In 28 nondialysis patients, the commonest cell type was clear cell carcinoma (67%) and acinar growth pattern was the predominant one (67%). The incidence of papillary renal cell tumors in dialysis patients was significantly higher than in nondialysis patients (p < 0.05). Patients with papillary renal cell tumors had received longer duration of dialysis therapy than those with nonpapillary renal cell carcinomas (p < 0.05). Seven (39%) showed grade 1 carcinoma and 11 (61%) showed grade 2, but grade 3 carcinoma was not observed. In these patients, 8 had associated acquired cystic disease of the kidney (ACDK). The duration of dialysis in the patients with ACDK was significantly longer (p < 0.001). The most frequent cell type was granular-cell carcinoma (63%) in the patients with ACDK. Six patients without ACDK (60%) showed clear-cell carcinoma and 4 (40%) had granular cell tumors. Seventy-four percent of carcinomas exhibited a predominantly either papillary or cystic growth pattern in the patients with ACDK. However, renal cell carcinomas in dialysis patients with or without ACDK did not show significant differences in growth pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

High incidence of papillary renal cell tumours in patients on chronic haemodialysis.

Papillary and nonpapillary renal cell tumours can be differentiated according to their genetic constitution. In this study, their incidence in end stage kidney disease has been investigated histologically. Nonpapillary renal cell carcinoma was observed in 22 cases (51.2%) whereas papillary renal cell tumours were diagnosed in 21 (48.8%) of the 43 patients with end stage kidney disease. The incidence of papillary renal cell tumours in end stage kidney disease is significantly higher (chi 2 = 31.9; P < 0.001) than in the general population (4.8%). Haemodialysis patients with nonpapillary and papillary renal cell tumours did not show significant differences in age, sex or size of tumour. However, patients with papillary renal cell tumours had received longer duration of haemodialysis than patients with nonpapillary renal cell carcinomas. These data suggest that not only different genetic events but also different aetiological factors are involved in the development of the two types of tumour in end stage kidney disease.

Molecular differential pathology of renal cell tumours.

Recent application of molecular cytogenetic techniques to the evaluation of renal cell tumours revealed four subtypes, each with a characteristic combination of genetic alterations within the chromosomal and mitochondrial DNA. The most common, nonpapillary renal cell carcinomas are characterized by the loss of chromosome 3p sequences, rearrangement of the chromosome 5q region and loss of the chromosome 14q sequences. Papillary renal cell tumours can be divided into two groups. Tumours with a combined trisomy of chromosomes 7 and 17 as well as loss of the Y chromosome are papillary renal cell adenomas. Tumours with additional trisomies such as trisomy 16, 20 or 12 are papillary renal cell carcinomas. Chromophobe renal cell carcinomas show a combination of allelic losses, which do not occur in other types of renal tumours. In addition, they have a rearrangement in the mitochondrial DNA. Renal oncocytomas are benign tumours marked by normal or abnormal karyotypes with balanced or unbalanced translocations and an altered restriction pattern of the mitochondrial DNA. Although the major cytological characteristics of renal cell tumours, such as clear, granular, chromophobe and oncocytic cell phenotypes correspond to nonpapillary, papillary and chromophobe renal cell carcinomas and renal oncocytomas, there are many cases with overlapping phenotype. Therefore, a classification of renal cell tumours based on specific genetic alterations is proposed.

Molecular Cytogenetics of Renal Cell Tumors

Publisher Summary The development and progression of cancer is associated with the alterations of genes that control growth and differentiation. The accumulation of genetic changes—such as inactivation of tumor suppressor genes—and the alteration of function of oncogenes, growth factors and their receptors, and genes related to metastatic growth characterize the multistep nature of tumor development. Renal cell carcinoma is the most common malignant tumor arising from the kidney. The cytogenetic analysis, especially in combination with DNA analysis, is a powerful technique to detect new tumor-associated genetic alterations. Molecular cytogenic methods are efficient to stratify renal cell tumors. This chapter emphasizes on the complexity of genetic alterations in the subtypes of renal cell tumors and indicates that specific genetic changes are useful in the diagnosis as well as in the separation of high-risk groups for therapy. The genetics of nonpapillary renal cell carcinomas include sporadic and familial renal cell carcinomas. The genetics of papillary renal cell tumors is also discussed in the chapter. A model of nonhomologous mitotic recombination in renal cell carcinomas is diagrammatically represented in the chapter. The renal oncocytoma and chromophobe renal cell carcinoma are also discussed in the chpater.

Cytogenetics of papillary renal cell tumors

Chromosome aberrations were determined in short-term cultures of 18 papillary renal cell tumors, as well as in the cell line ACHN, and the results were evaluated together with 20 previously published cases. We found that chromosomes 7, 17, and 16 and the Y chromosome were specifically involved in the karyotype changes, marks benign papillary renal cell adenomas (ten cases). Malignant papillary renal cell carcinomas (29 cases) were characterized by additional trisomies: trisomy 16 occurred in 20 tumors, and trisomy 12 and 20 in 8 tumors each. Loss of the Y chromosome was observed in 7 of 9 benign and in 23 of 25 malignant tumors that developed in males. None of the papillary renal cell adenomas or carcinomas showed a loss of 3p or gain of a 5q segment, both of which are characteristic of common non-papillary renal cell carcinomas.