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CGH patterns in head and neck squamous cell carcinomas
156
Abstracts
Poster Presentations: Session A A1
C O R R E L A T I O N S B E T W E E N C Y T O G E N E T I C FINDINGS AND H I S T O L O G Y BASED O N 382 BENIGN T H Y R O I D HYERPLASIAS AND ADENOMAS G. Belge 1, L. Roque 2, J. Soares 2, S. Bmckmann I , B. Thede 3, E. Fonseca 4, A. Ciode 2, S. Bartnitzke 1, S. Castedo 4, J. Bullerdiek 1 I Center for Human Genetics and Genetic Counselling, University of Bremen, Germany 2 Department of Morphological Pathology of the Portuguese Institute for Oncology, Lisbea, Portugal; 3Department of Pathology, The Central Hospital St.-Jiargen-Str., Bremen, Germany; 4Department of Medical Genetics, IPATMUP, Medical Faculty of Porto, Portugal Thyroid tumors and goiters belong to a large number of human benign lesions showing recurrent chromosome abnormalities. Here we present the results of 382 benign thyroid lesions from 260 patients and correlate these results with the histological examinations. Cell cultures of 382 benign thyroid hyperplasias and adenomas were set up. O f these, 42 cases failed to grow and cytogenetic studies were possible in 340 cases. Clonal chromosome changes were found in 67 cases. Trisomy 7 as the sole abnormality or along with other trisomies was the most frequent type of aberration (19 cases). Other recurrent numerical changes were loss of chromosome 22 (4 cases) and the second X or the Y chromosome (5 cases). Translocations involving 19q13 (12 cases) were frequent structural chromosome changes. Dicentric chromosomes or telomeric associations were frequent in goiters (12 cases). After a histological classification of all cases, we have correlated the cytogenetic findings with the histology of the tumors. Only 8.4 percent of the goiters showed clonal abnormalities whereas 44.9 percent of the adenomas revealed clonal abnormalities. Furthermore, simple clonal changes were predominantly found in goiters and complex changes in adenomas. The most impressive correlation however, was found in the group of lesions with trisomy 7: Whereas all but one lesion with one or two additional trisomies were goiters those having three or more additional trisomies were all adenomas or adenomatous goiters.
A2
ASSESSMENT O F N U M E R I C A L C H R O M O S O M E A B N O R M A L I T I E S IN T H Y R O I D N E O P L A S I A BY F L U O R E S C E N C E IN SITU HYBRIDIZATION. A.W. Block. J.M. Peterseo, T. Loree, W. Hicks, M.D. Delacure, N.J. Fetrclli. Clinical Cytogenetics Laboratory, Division of Pathology; Departments of Head and Neck Surgery/Surgical Oncology, Division of Surgery. Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, New York 14263. Differentiated carcinoma of the thyroid gland is a neoplasm with a clinical behavior which is often paradoxical and unlike that of other human cancers. Some tumors have an indolent course. Others behave in an aggressive manner with high morbidity and mortality. These tumors may represent a model for human epithelial cell multistep carcinogenesis. In an attempt to characterize specific numerical chromosome abnormalities in thyroid carcinomas and correlate with histology and clinical behavior we present here the preliminary findings from a prospective study of 41 patients undergoing thyroidectomy at our institution. Fluorescence in situ hybridization (FISH) studies were performed on fresh surgical touch prep material using centromere specific probes for chromosomes #7, 8, 9, and 12. Forty-two samples were obtained for analysis, including normal thyroid gland (2), follicular adenoma (2), thyroiditis and/or non-toxic nodular goiter (18, including 4 with microscopic foni of incidental papillary carcinoma) and papillary carcinoma (20). For each of the four chromosomes studied, the percentage of diploidy and aneuploidy were determined for each sample. The mean and ranges were then determined for each chromosome for the entire sample group. The mean percentages of diploid cells were 87.7, 87.6, 87.1 and 86.5 for chromosomes #7, 8, 9, and 12, respectively. Benign samples were compared to malignant samples using the Fisher-Exact statistical test. The number of samples above and below the overall diploid mean in each group and for each chromosome were determined. The results showed a highly significant percentage of aneuploidy for chromosomes #7, 8 and 12. This finding of aneuploidy supports the suggestion that multiple chromosome changes may be contributory to the development of malignancy.
A3
C G H PATTERNS I N H E A D AND N E C K SQUAMOUS C E L L CARCINOMAS U Bockmithi. A Schwendel I, M Dietel 1,1 Petersen l Department of Otorhinolaryngology and llnstitote of Pathology, Charite-Hospital, Humboldt-University, Schumannstr. 20-21, 10098 Berlin, Germany Comparative Genomic Hybridization (CGH) was performed on 31 primary head and neck squamous cell carcinomas. Fractional or entire DNA loss of chromosome 3p were a basic finding that occured in 30 cases (97 percent). Additional DNA underrepresentations were observed in more than 50 percent of cases on chromosomes lp, 4, 5q, 6q, 8p, 9p, llq, 13q, 18q and 21q. Deletions on chromosomes 3p, 13q and 17p were confirmed by LOH analysis. Entire or partial DNA copy number increases were identified for chromosome 3q in 26 cases (87 percent) with high level amplifications at 3q24 and 3q27-qter. Overrepresontations were found in decreasing order of frequency at 11q13 (70 percent), 8q (57 percent), 19q (50 percent), 19p (47 percent) and 17q (47 percent). The use of CGH super-karyograms of the group of well differentiated carcinomas (G1) indicated that the deletion on chromosomes 3p and 9p together with the overrepresentation of 3q are associated with early tumor development. Accordingly, the undifferentiated tumors (G3) were charaterized by addtional deletions on chromosomes 4q, 8p, llq, 13q, 18q, 21q and overrepresentations on lp, llql3, 19 and 22q.
A/I I N C I D E N C E O F C A N C E R IN ITALIAN ATAXIA TELANGIECTASIA .c'/k"J£ FAMILIES L. Cbessa. S. Prudente, M. Piane, G. Zei*,Dept. of Experimental Medicine and Pathology, University "La Sapienza", Rama and *IGBE-CNR, Pavia Ataxia Telangiectasia (AT) is an autosomal recessive disease characterized by progressive cere bellar ataxia, oculocutaneous telangiectasias, immunodeficiency, radiosensitivity and high incidence of cancer, especially lymphomas and leukemia, in affected individuals. The incidence of cancer in AT families has been reported to be higher than in general population (Swift et al., 19 ). Until the identification of the AT gene, termedATM (Savitsky et al., 1995), there was no possibility to correlate the epidemiologic data on the cancer incidence in AT families with the heterozygnsity for the AT gene except for the parents of affected individuals. In Italy a Registry for Ataxia Telangieetasia, collecting most of the Italian AT cases, was established since 1986 together with a Cell Repository. Previous epidemiological studies (Chessa and Fiorilli, 1993; Chessa et al., 1994) confirmed the high incidence of cancer in AT patients and their relatives. AT patients died for lynphoma, leukemia and rarely for carcinoma or menin gioma. The most frequent type of cancer in AT relatives was gastric carcinoma (relative risk of 36 for males and 46 for females), followed by colon carcinoma (relative risk of 28 in beth sexes) and breast carcinoma (relative risk of 28.8 for women in AT families). Since the A TM has been cloned 21 different mutations have been identified in 31 Italian AT patients ( Savitsky et al., 1995; Gilad et al., 1996; personal data). The recovery of these mutations allowed us to perform segregation analysis in the AT families in order to correlate the beterozygnsity status with the epidemiologic data on cancer incidence. Until now only few families were studied, while the molecular analysis is in progress for many others. Preliminary data do not allow us any conclusion. This work was partially granted by Italian CNR, PF ACRO, and Telethon E.337.
Abstracts
Poster Presentations: Session A A1
C O R R E L A T I O N S B E T W E E N C Y T O G E N E T I C FINDINGS AND H I S T O L O G Y BASED O N 382 BENIGN T H Y R O I D HYERPLASIAS AND ADENOMAS G. Belge 1, L. Roque 2, J. Soares 2, S. Bmckmann I , B. Thede 3, E. Fonseca 4, A. Ciode 2, S. Bartnitzke 1, S. Castedo 4, J. Bullerdiek 1 I Center for Human Genetics and Genetic Counselling, University of Bremen, Germany 2 Department of Morphological Pathology of the Portuguese Institute for Oncology, Lisbea, Portugal; 3Department of Pathology, The Central Hospital St.-Jiargen-Str., Bremen, Germany; 4Department of Medical Genetics, IPATMUP, Medical Faculty of Porto, Portugal Thyroid tumors and goiters belong to a large number of human benign lesions showing recurrent chromosome abnormalities. Here we present the results of 382 benign thyroid lesions from 260 patients and correlate these results with the histological examinations. Cell cultures of 382 benign thyroid hyperplasias and adenomas were set up. O f these, 42 cases failed to grow and cytogenetic studies were possible in 340 cases. Clonal chromosome changes were found in 67 cases. Trisomy 7 as the sole abnormality or along with other trisomies was the most frequent type of aberration (19 cases). Other recurrent numerical changes were loss of chromosome 22 (4 cases) and the second X or the Y chromosome (5 cases). Translocations involving 19q13 (12 cases) were frequent structural chromosome changes. Dicentric chromosomes or telomeric associations were frequent in goiters (12 cases). After a histological classification of all cases, we have correlated the cytogenetic findings with the histology of the tumors. Only 8.4 percent of the goiters showed clonal abnormalities whereas 44.9 percent of the adenomas revealed clonal abnormalities. Furthermore, simple clonal changes were predominantly found in goiters and complex changes in adenomas. The most impressive correlation however, was found in the group of lesions with trisomy 7: Whereas all but one lesion with one or two additional trisomies were goiters those having three or more additional trisomies were all adenomas or adenomatous goiters.
A2
ASSESSMENT O F N U M E R I C A L C H R O M O S O M E A B N O R M A L I T I E S IN T H Y R O I D N E O P L A S I A BY F L U O R E S C E N C E IN SITU HYBRIDIZATION. A.W. Block. J.M. Peterseo, T. Loree, W. Hicks, M.D. Delacure, N.J. Fetrclli. Clinical Cytogenetics Laboratory, Division of Pathology; Departments of Head and Neck Surgery/Surgical Oncology, Division of Surgery. Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, New York 14263. Differentiated carcinoma of the thyroid gland is a neoplasm with a clinical behavior which is often paradoxical and unlike that of other human cancers. Some tumors have an indolent course. Others behave in an aggressive manner with high morbidity and mortality. These tumors may represent a model for human epithelial cell multistep carcinogenesis. In an attempt to characterize specific numerical chromosome abnormalities in thyroid carcinomas and correlate with histology and clinical behavior we present here the preliminary findings from a prospective study of 41 patients undergoing thyroidectomy at our institution. Fluorescence in situ hybridization (FISH) studies were performed on fresh surgical touch prep material using centromere specific probes for chromosomes #7, 8, 9, and 12. Forty-two samples were obtained for analysis, including normal thyroid gland (2), follicular adenoma (2), thyroiditis and/or non-toxic nodular goiter (18, including 4 with microscopic foni of incidental papillary carcinoma) and papillary carcinoma (20). For each of the four chromosomes studied, the percentage of diploidy and aneuploidy were determined for each sample. The mean and ranges were then determined for each chromosome for the entire sample group. The mean percentages of diploid cells were 87.7, 87.6, 87.1 and 86.5 for chromosomes #7, 8, 9, and 12, respectively. Benign samples were compared to malignant samples using the Fisher-Exact statistical test. The number of samples above and below the overall diploid mean in each group and for each chromosome were determined. The results showed a highly significant percentage of aneuploidy for chromosomes #7, 8 and 12. This finding of aneuploidy supports the suggestion that multiple chromosome changes may be contributory to the development of malignancy.
A3
C G H PATTERNS I N H E A D AND N E C K SQUAMOUS C E L L CARCINOMAS U Bockmithi. A Schwendel I, M Dietel 1,1 Petersen l Department of Otorhinolaryngology and llnstitote of Pathology, Charite-Hospital, Humboldt-University, Schumannstr. 20-21, 10098 Berlin, Germany Comparative Genomic Hybridization (CGH) was performed on 31 primary head and neck squamous cell carcinomas. Fractional or entire DNA loss of chromosome 3p were a basic finding that occured in 30 cases (97 percent). Additional DNA underrepresentations were observed in more than 50 percent of cases on chromosomes lp, 4, 5q, 6q, 8p, 9p, llq, 13q, 18q and 21q. Deletions on chromosomes 3p, 13q and 17p were confirmed by LOH analysis. Entire or partial DNA copy number increases were identified for chromosome 3q in 26 cases (87 percent) with high level amplifications at 3q24 and 3q27-qter. Overrepresontations were found in decreasing order of frequency at 11q13 (70 percent), 8q (57 percent), 19q (50 percent), 19p (47 percent) and 17q (47 percent). The use of CGH super-karyograms of the group of well differentiated carcinomas (G1) indicated that the deletion on chromosomes 3p and 9p together with the overrepresentation of 3q are associated with early tumor development. Accordingly, the undifferentiated tumors (G3) were charaterized by addtional deletions on chromosomes 4q, 8p, llq, 13q, 18q, 21q and overrepresentations on lp, llql3, 19 and 22q.
A/I I N C I D E N C E O F C A N C E R IN ITALIAN ATAXIA TELANGIECTASIA .c'/k"J£ FAMILIES L. Cbessa. S. Prudente, M. Piane, G. Zei*,Dept. of Experimental Medicine and Pathology, University "La Sapienza", Rama and *IGBE-CNR, Pavia Ataxia Telangiectasia (AT) is an autosomal recessive disease characterized by progressive cere bellar ataxia, oculocutaneous telangiectasias, immunodeficiency, radiosensitivity and high incidence of cancer, especially lymphomas and leukemia, in affected individuals. The incidence of cancer in AT families has been reported to be higher than in general population (Swift et al., 19 ). Until the identification of the AT gene, termedATM (Savitsky et al., 1995), there was no possibility to correlate the epidemiologic data on the cancer incidence in AT families with the heterozygnsity for the AT gene except for the parents of affected individuals. In Italy a Registry for Ataxia Telangieetasia, collecting most of the Italian AT cases, was established since 1986 together with a Cell Repository. Previous epidemiological studies (Chessa and Fiorilli, 1993; Chessa et al., 1994) confirmed the high incidence of cancer in AT patients and their relatives. AT patients died for lynphoma, leukemia and rarely for carcinoma or menin gioma. The most frequent type of cancer in AT relatives was gastric carcinoma (relative risk of 36 for males and 46 for females), followed by colon carcinoma (relative risk of 28 in beth sexes) and breast carcinoma (relative risk of 28.8 for women in AT families). Since the A TM has been cloned 21 different mutations have been identified in 31 Italian AT patients ( Savitsky et al., 1995; Gilad et al., 1996; personal data). The recovery of these mutations allowed us to perform segregation analysis in the AT families in order to correlate the beterozygnsity status with the epidemiologic data on cancer incidence. Until now only few families were studied, while the molecular analysis is in progress for many others. Preliminary data do not allow us any conclusion. This work was partially granted by Italian CNR, PF ACRO, and Telethon E.337.