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Cytogenetic, Flow Cytometric, and Ultrastructural Studies of Twenty-Nine Nonfamilial Human Renal Carcinomas
RENAL TUMORS, RETROPERITONEUM, DIVERSION AND RECONSTRUCTION
diagnosis of renal cell carcinoma variants, including renal oncocytoma, spindle cell tumors, metastatic renal cell carcinoma and also the diagnosis of neuroblastoma. Frequently, with a small needle aspirate of a mass it may be difficult to determine the primary neoplasm. On the other hand, with immunohistochemical techniques various patterns can be predictive. According to Wick and associates the sarcomatoid neoplasm that lacks desmin and actin but manifests cytokeratin or epithelial membrane antigen with or without vimentin can be considered epithelial. In other instances it may be possible to differentiate metastatic renal cell and thyroid carcinoma (Domagala and associates) or an oncocytoma from a renal cell carcinoma (Van Krieken and associates). Lastly, in neuroblastoma more specific markers may be present with neuron specific enolase. This finding may help to diagnose neuroblastoma (Silverman and associates). Identification of the primary tumor may dictate therapy. As a result, these new techniques may be helpful in select circumstances. Fray F. Marshall, M.D.
'71 4·/.l.
Of the 21 tumors with abnormal chromosomes, the most frequent abnormality was either trisomy or tetrasomy of chromosome 7 (18 of 21 tumors). In four of these tumors, trisomy 7 was the only visible abnormality. Ten tumors contained abnormalities of chromosome 3. Three showed a previously reported chromosome 3 interstitial deletion, five were hyperdiploid, and two revealed a monosomy 3. Of these 10 patients, six have had disease progression, compared to one of the 16 remaining patients without an abnormal chromosome 3. These data suggest that abnormalities of chromosome 7 represent a primary abnormality, and that when these abnormalities are present in association with abnormalities involving chromosome 3, they may correlate with a more aggressive clinical course and a corresponding higher stage of disease at diagnosis.
Cytogenetic, Flow Cytometric, and Ultrastructural Studies of Twenty-Nine Nonfamilial Human Renal Carcinomas
S. R. Direct Molecular Analysis of a Deletion of 3p in Tumors From Patients With Sporadic Renal Cell Carcinoma A. H. VAN DER HOUT, K. KOK, A VAN DEN BERG, J. W. 00STERHUIS, B. CARRITT AND C. H. C. M. BUYS, Departments of Hum.an Genetics and Pathology, State University of Groningen, Groningen, The Netherlands and MRC Human Biochemical Unit, University College, London, England Cancer Genet. Cytogenet., 32: 281-285, 1988 Normal and tumorous nephrectomy specimens from seven renal cell carcinoma patients were subjected to a Southern analysis using chromosome #3-specific polymorphic probes. Three patients were not informative because of homozygosity at all loci studied. One patient showing heterozygosity at 3q in normal tissue had a tumor that remained heterozygous. In three patients the tumor showed loss of heterozygosity for a short arm marker at 3p2L In one of them heterozygosity for a second short arm marker was also lost. Another of these three patients retained heterozygosity for this second short arm marker, as well as for a long arm marker, suggesting a chromosomal breakpoint between the loci for the two short arm markers. Our results demonstrate that the known involvement of a short arm region of chromosome #3 in the development of renal cell carcinoma can readily be further evaluated by direct molecular methods. Cytogenetic Analysis in Renal Cell Carcill:l.oma: Correlation With Tumor Aggressiveness D. J. WEAVER, K. MICHALSKI AND J. MILES, Division of Urology, Departments of Surgery, Child Health and Pathology, University of Missouri Medical Center, and Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri Cancer Res., 48: 2887-2889, 1988 Twenty-eight tissue specimens from 26 patients with renal cell carcinoma were subjected to cytogenetic analysis using a newly developed combined method of enzymatic technique and short term tissue culture. Of the 28 tumor samples studied, 21 were chromosomally abnormal. Four (including two oncocytomas) were normal, and three did not grow in tissue culture.
WOLMAN, P. M. CAMUTO, M. GOLIMBU AND R. SCHINELLA, Departments of Pathology and Urology, Bellevue
Hospital-New York University Medical Center, New York, New York Cancer Res., 48: 2890-2897, 1988 Multifactorial analysis, including cytogenetic studies, flow cytometry, and light and electron microscopic evaluation, was performed on 29 primary renal cell carcinomas and short-term cultures derived from them. Eleven of the 21 cases that yielded cytogenetic results demonstrated clonal chromosomal aberrations which included trisomy 7 in 8 cases, loss of the Y chromosome in 7, trisomy 12 in 2, and 16q- in L Flow cytometry showed that there was preferential growth of near-diploid populations and loss of aneuploid clones in culture with standard media. The ultrastructural features of both the primary and cultured tumors were remarkably similar. They included cytoplasmic vacuolization, reticulated dense nucleoli, and cell surface microvilli. Thus, morphological evidence supported the epithelial and, specifically, the renal tubular origin of the cultured cells. The development of chromosomal abnormalities seemed linked to advanced tumor stage, but the number of such cases was too small to analyze for statistical significance. No other correlations could be made between karyotypic change, DNA analysis, tumor histology, grade, and stage at this point in the patient follow-up. Tumor Spread and DNA Content in Human Renal Cell Carcinoma G. Roos, Departments of Urology and Andrology, and Pathology, University of Um.ea, Umea, Sweden
B. LJUNGBERG, R. 8TENLING AND
Cancer Res., 48: 3165-3167, 1987 Local and distant tumor spread was evaluated and compared with DNA content analyzed by flow cytometry of eight samples from each of 71 renal cell carcinomas. Twenty-six tumors were homogenously diploid while 45 tumors contained at least one aneuploid tumor sample. Diploid tumors generally respected the surrounding tissues and only three of 26 tumors (12%) had evidence of local tumor invasion. In contrast, 33 of 45 patients (73%) with aneuploid tumors had local invasion (p < 0.001).
diagnosis of renal cell carcinoma variants, including renal oncocytoma, spindle cell tumors, metastatic renal cell carcinoma and also the diagnosis of neuroblastoma. Frequently, with a small needle aspirate of a mass it may be difficult to determine the primary neoplasm. On the other hand, with immunohistochemical techniques various patterns can be predictive. According to Wick and associates the sarcomatoid neoplasm that lacks desmin and actin but manifests cytokeratin or epithelial membrane antigen with or without vimentin can be considered epithelial. In other instances it may be possible to differentiate metastatic renal cell and thyroid carcinoma (Domagala and associates) or an oncocytoma from a renal cell carcinoma (Van Krieken and associates). Lastly, in neuroblastoma more specific markers may be present with neuron specific enolase. This finding may help to diagnose neuroblastoma (Silverman and associates). Identification of the primary tumor may dictate therapy. As a result, these new techniques may be helpful in select circumstances. Fray F. Marshall, M.D.
'71 4·/.l.
Of the 21 tumors with abnormal chromosomes, the most frequent abnormality was either trisomy or tetrasomy of chromosome 7 (18 of 21 tumors). In four of these tumors, trisomy 7 was the only visible abnormality. Ten tumors contained abnormalities of chromosome 3. Three showed a previously reported chromosome 3 interstitial deletion, five were hyperdiploid, and two revealed a monosomy 3. Of these 10 patients, six have had disease progression, compared to one of the 16 remaining patients without an abnormal chromosome 3. These data suggest that abnormalities of chromosome 7 represent a primary abnormality, and that when these abnormalities are present in association with abnormalities involving chromosome 3, they may correlate with a more aggressive clinical course and a corresponding higher stage of disease at diagnosis.
Cytogenetic, Flow Cytometric, and Ultrastructural Studies of Twenty-Nine Nonfamilial Human Renal Carcinomas
S. R. Direct Molecular Analysis of a Deletion of 3p in Tumors From Patients With Sporadic Renal Cell Carcinoma A. H. VAN DER HOUT, K. KOK, A VAN DEN BERG, J. W. 00STERHUIS, B. CARRITT AND C. H. C. M. BUYS, Departments of Hum.an Genetics and Pathology, State University of Groningen, Groningen, The Netherlands and MRC Human Biochemical Unit, University College, London, England Cancer Genet. Cytogenet., 32: 281-285, 1988 Normal and tumorous nephrectomy specimens from seven renal cell carcinoma patients were subjected to a Southern analysis using chromosome #3-specific polymorphic probes. Three patients were not informative because of homozygosity at all loci studied. One patient showing heterozygosity at 3q in normal tissue had a tumor that remained heterozygous. In three patients the tumor showed loss of heterozygosity for a short arm marker at 3p2L In one of them heterozygosity for a second short arm marker was also lost. Another of these three patients retained heterozygosity for this second short arm marker, as well as for a long arm marker, suggesting a chromosomal breakpoint between the loci for the two short arm markers. Our results demonstrate that the known involvement of a short arm region of chromosome #3 in the development of renal cell carcinoma can readily be further evaluated by direct molecular methods. Cytogenetic Analysis in Renal Cell Carcill:l.oma: Correlation With Tumor Aggressiveness D. J. WEAVER, K. MICHALSKI AND J. MILES, Division of Urology, Departments of Surgery, Child Health and Pathology, University of Missouri Medical Center, and Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri Cancer Res., 48: 2887-2889, 1988 Twenty-eight tissue specimens from 26 patients with renal cell carcinoma were subjected to cytogenetic analysis using a newly developed combined method of enzymatic technique and short term tissue culture. Of the 28 tumor samples studied, 21 were chromosomally abnormal. Four (including two oncocytomas) were normal, and three did not grow in tissue culture.
WOLMAN, P. M. CAMUTO, M. GOLIMBU AND R. SCHINELLA, Departments of Pathology and Urology, Bellevue
Hospital-New York University Medical Center, New York, New York Cancer Res., 48: 2890-2897, 1988 Multifactorial analysis, including cytogenetic studies, flow cytometry, and light and electron microscopic evaluation, was performed on 29 primary renal cell carcinomas and short-term cultures derived from them. Eleven of the 21 cases that yielded cytogenetic results demonstrated clonal chromosomal aberrations which included trisomy 7 in 8 cases, loss of the Y chromosome in 7, trisomy 12 in 2, and 16q- in L Flow cytometry showed that there was preferential growth of near-diploid populations and loss of aneuploid clones in culture with standard media. The ultrastructural features of both the primary and cultured tumors were remarkably similar. They included cytoplasmic vacuolization, reticulated dense nucleoli, and cell surface microvilli. Thus, morphological evidence supported the epithelial and, specifically, the renal tubular origin of the cultured cells. The development of chromosomal abnormalities seemed linked to advanced tumor stage, but the number of such cases was too small to analyze for statistical significance. No other correlations could be made between karyotypic change, DNA analysis, tumor histology, grade, and stage at this point in the patient follow-up. Tumor Spread and DNA Content in Human Renal Cell Carcinoma G. Roos, Departments of Urology and Andrology, and Pathology, University of Um.ea, Umea, Sweden
B. LJUNGBERG, R. 8TENLING AND
Cancer Res., 48: 3165-3167, 1987 Local and distant tumor spread was evaluated and compared with DNA content analyzed by flow cytometry of eight samples from each of 71 renal cell carcinomas. Twenty-six tumors were homogenously diploid while 45 tumors contained at least one aneuploid tumor sample. Diploid tumors generally respected the surrounding tissues and only three of 26 tumors (12%) had evidence of local tumor invasion. In contrast, 33 of 45 patients (73%) with aneuploid tumors had local invasion (p < 0.001).