Abstract
Background
The adrenal gland may give rise to pheochromocytomas, which are catecholamine-producing tumors originating from the adrenal medulla, or to adrenocortical tumors, which derive from the adrenocortical cortex and may be secreting or not. The genetic mechanisms underlying the formation of these tumors include somatic mutations in susceptibility genes, especially in the familial forms, and allelic loss, especially in chromosome 1.
Aim
The aim of this study was to investigate a third genetic mechanism by evaluating microsatellite instability using the reference markers (Bat25, Bat26, D2S123, D5S346, D17S250) validated by the National Cancer Institute. Microsatellite loci were analyzed in 32 benign tumors, including 11 pheochromocytomas and 21 adrenocortical tumors, in patients with and without familial syndrome.
Results
The different alleles of microsatellite loci were reliably detected by DNA fragments analysis, whereas data obtained after melting-point analysis on the Lightcycler were inconsistent. No microsatellite instability was detected in any tumor. One patient with a unilateral pheochromocytoma showed a loss of heterozygosity for D17S250. A second patient with a MEN-2A syndrome and a two-sided pheochromocytoma exhibited a loss of heterozygosity for D2S123 in the right tumor only and a retention of heterozygosity for all markers in the left tumor.
Conclusions
These results suggest that microsatellite instability, evaluated by the five reference markers of the National Cancer Institute, is not a feature of benign adrenal tumors.
Similar content being viewed by others
References
Eng C, Crossey PA, Mulligan LM, et al. Mutations in the RET proto-oncogene and the von Hippel-Lindau disease tumour suppressor gene in sporadic and syndromic phaeochromocytomas. J Med Genet 1995;32:934–937
Bar M, Friedman E, Jakobovitz O, et al. Sporadic phaeochromocytomas are rarely associated with germline mutations in the von Hippel-Lindau and RET genes. Clin Endocrinol 1997;47:707–712
Rodien P, Jeunemaitre X, Dumont C, et al. Genetic alterations of the RET proto-oncogene in familial and sporadic pheochromocytomas. Horm Res 1997;47:263–268
Benn DE, Dwight T, Richardson AL, et al. Sporadic and familial pheochromocytomas are associated with loss of at least two discrete intervals on chromosome 1p. Cancer Res 2000;15:7048–7051
Opocher G, Schiavi F, Vettori A, et al. Fine analysis of the short arm of chromosome 1 in sporadic and familial pheochromocytoma. Clin Endocrinol 2003;59:707–715
Edstrom Elder E, Nord B, Carling T, et al. Loss of heterozygosity on the short arm of chromosome 1 in pheochromocytoma and abdominal paraganglioma. World J Surg 2002;26:965–971
Carling T, Du Y, Fang W, et al. Intragenic allelic loss and promoter hypermethylation of the RIZI1 tumor suppressor gene in parathyroid tumors and pheochromocytomas. Surgery 2003;134:932–939
Geli J, Nord B, Frisk T, et al. Deletions and altered expression of the RIZ1 tumour suppressor gene in 1p36 in pheochromocytomas and abdominal paragangliomas. Int J Oncol 2005;26:1385–1391
Edstrom E, Mahlamaki E, Nord B, et al. Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromocytomas and abdominal paragangliomas, suggesting a common genetic etiology. Am J Pathol 2000;156:651–659
Bertherat J, Gimenez-Roqueplo AP. New insights in the genetics of adrenocortical tumors, pheochromocytomas and paragangliomas. Horm Metab Res 2005;37:384–390
Sidhu S, Gicquel C, Bambach CP, et al. Clinical and molecular aspects of adrenocortical tumourigenesis. Aust N Z J Surg 2003;73:727–738
Kloor M, von Knebel, Doeberitz M, et al. Molecular testing for microsatellite instability and its value in tumor characterization. Expert Rev Mol Diagn 2005;5:599–611
Lawes DA, SenGupta S, Boulos PB. The clinical importance and prognostic implications of microsatellite instability in sporadic cancer. Eur J Surg Oncol 2003;29:201–212
Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003;349:247–257
Kaneki E, Oda Y, Ohishi Y, et al. Frequent microsatellite instability in synchronous ovarian and endometrial adenocarcinoma and its usefulness for differential diagnosis. Hum Pathol 2004;35:1484–1493
Musulen E, Moreno V, Reyes G, et al. Standardized approach for microsatellite instability detection in gastric carcinomas. Hum Pathol 2004;35:335–342
Chen Y, Wang J, Fraig MM, et al. Defects of DNA mismatch repair in human prostate cancer. Cancer Res 2001;61:4112–4121
Hartmann A, Zanardo L, Bocker-Edmonston T, et al. Frequent microsatellite instability in sporadic tumors of the upper urinary tract. Cancer Res 2002;62:6796–6802
Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998;58:5248–5257
Dietmaier W, Hofstadter F. Detection of microsatellite instability by real time PCR and hybridization probe melting point analysis. Lab Invest 2001;81:1453–1456
Neumann HP, Pawlu C, Peczkowska M, et al. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations J Am Med Assoc 2004;292:943–951
Sood AK, Holmes R, Hendrix MJ, et al. Application of the National Cancer Institute international criteria for determination of microsatellite instability in ovarian cancer. Cancer Res 2001;61:4371–4374
Rugge M, Bersani G, Bertorelle R, et al. Microsatellite instability and gastric non-invasive neoplasia in a high risk population in Cesena, Italy. J Clin Pathol 2005;58:805–810
Saetta AA, Gigelou F, Papanastasiou PI, et al. High-level microsatellite instability is not involved in gallbladder carcinogenesis. Exp Mol Pathol 2006;80:67–71
Mallya SM, Gallagher JJ, Arnold A. Analysis of microsatellite instability in sporadic parathyroid adenomas. J Clin Endocrinol Metab 2003;88:1248–1251
Pecina-Slaus N, Nikuseva-Martic T, Gall-Troselj K, et al. Replication error-positive samples found in pheochromocytomas. In Vivo 2005;19:359–365
Dietmaier W, Wallinger S, Bocker T, et al. Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 1997;57:4749–4756
Bocker T, Diermann J, Friedl W, et al. Microsatellite instability analysis: a multicenter study for reliability and quality control. Cancer Res 1997;57:4739–4743
Zhou XP, Hoang JM, Cottu P, et al. Allelic profiles of mononucleotide repeat microsatellites in control individuals and in colorectal tumors with and without replication errors. Oncogene 1997;15:1713–1718
Hoang JM, Cottu PH, Thuille B, et al. BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. Cancer Res 1997;57:300–303
Pyatt R, Chadwick RB, Johnson CK, et al. Polymorphic variation at the BAT-25 and BAT-26 loci in individuals of African origin. Am J Pathol 1999;155:349–353
Luqmani YA, Mathew M. Allelic variation of BAT-25 and BAT-26 mononucleotide repeat loci in tumours from a group of young women with breast cancer. Int J Oncol 2004;25:771–775
Kim HS, Lee BL, Woo DK, et al. Assessment of markers for the identification of microsatellite instability phenotype in gastric neoplasms. Cancer Lett 2001;164:61–68
Loukola A, Eklin K, Laiho P, et al. Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC). Cancer Res 2001;61:4545–4549
Suraweera N, Duval A, Reperant M, et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 2002;123:1804–1811
Acknowledgments
We thank Dr Anne Schneider (Laboratoire de Biochimie, Hôpital de Haute Pierre, Strasbourg) for valuable discussions and for kindly providing DNA from MSI-positive colon carcinomas. We thank Olfert Landt from Tib-Molbiol, Berlin, Germany, for helpful discussions and recommendations concerning the Hyprobes/FRET technology. This work was supported by a grant from Ligue Contre le Cancer, Comité Départemental de Meurthe et Moselle.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Namour, F., Ayav, A., Lu, X. et al. Lack of Association between Microsatellite Instability and Benign Adrenal Tumors. World J. Surg. 30, 1240–1246 (2006). https://doi.org/10.1007/s00268-005-0471-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-005-0471-5