Abstract
The investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have therefore applied the technique of interphase cytogenetics to paraffin-embedded archival specimens of 14 adrenocortical adenomas and 13 carcinomas. Hybridizations were performed using centromere-specific probes to chromosomes 3, 4, 9, 17, 18 and X, which have been shown to be altered in other types of tumours. Chromosomal imbalance was defined on the basis of changes in both chromosome index (CI) and signal distribution (SD). Where only one of these was altered, this was classified as a tendency to gain or loss. On the basis of the analysis of optimal hybridizations, carcinomas showed gains in all chromosomes studied, five of nine showing gains in multiple chromosomes. Gains were most common in chromosomes 3, 9 and, in particular X, eight of 11 showing gain, and one a tendency to gain. Chromosomal gain was seen less commonly in adenomas, but again chromosomes 3, 9 and X were involved. Losses were infrequent, only one carcinoma showing loss of chromosome 18, and adenomas showing a tendency to loss of chromosomes 4 (two cases), 17 (one case) and 18 (two cases). Our data suggest that changes in chromosomes 3, 9 and X are early events in adrenocortical tumorigenesis, and that there is increasing chromosomal instability with tumour progression. © 1999 Cancer Research Campaign
Keywords: adrenal cortex; neoplasm; interphase cytogenetics; chromosomes 3, 9, X; imbalance
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- Baretton G. B., Valina C., Vogt T., Schneiderbanger K., Diebold J., Löhrs U. Interphase cytogenetic analysis of prostatic carcinomas by use of nonisotopic in situ hybridization. Cancer Res. 1994 Aug 15;54(16):4472–4480. [PubMed] [Google Scholar]
- Bulten J., Poddighe P. J., Robben J. C., Gemmink J. H., de Wilde P. C., Hanselaar A. G. Interphase cytogenetic analysis of cervical intraepithelial neoplasia. Am J Pathol. 1998 Feb;152(2):495–503. [PMC free article] [PubMed] [Google Scholar]
- Cornelisse C. J., Kuipers-Dijkshoorn N., van Vliet M., Hermans J., Devilee P. Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss. Int J Cancer. 1992 Feb 20;50(4):544–548. doi: 10.1002/ijc.2910500408. [DOI] [PubMed] [Google Scholar]
- Devilee P., Schuuring E., van de Vijver M. J., Cornelisse C. J. Recent developments in the molecular genetic understanding of breast cancer. Crit Rev Oncog. 1994;5(2-3):247–270. doi: 10.1615/critrevoncog.v5.i2-3.70. [DOI] [PubMed] [Google Scholar]
- Dhingra K., Sneige N., Pandita T. K., Johnston D. A., Lee J. S., Emami K., Hortobagyi G. N., Hittelman W. N. Quantitative analysis of chromosome in situ hybridization signal in paraffin-embedded tissue sections. Cytometry. 1994 Jun 1;16(2):100–112. doi: 10.1002/cyto.990160203. [DOI] [PubMed] [Google Scholar]
- Dobbie J. W. Adrenocortical nodular hyperplasia: the ageing adrenal. J Pathol. 1969 Sep;99(1):1–18. doi: 10.1002/path.1710990102. [DOI] [PubMed] [Google Scholar]
- Feng J., Funk W. D., Wang S. S., Weinrich S. L., Avilion A. A., Chiu C. P., Adams R. R., Chang E., Allsopp R. C., Yu J. The RNA component of human telomerase. Science. 1995 Sep 1;269(5228):1236–1241. doi: 10.1126/science.7544491. [DOI] [PubMed] [Google Scholar]
- Guo W., Burris T. P., Zhang Y. H., Huang B. L., Mason J., Copeland K. C., Kupfer S. R., Pagon R. A., McCabe E. R. Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1996 Jul;81(7):2481–2486. doi: 10.1210/jcem.81.7.8675564. [DOI] [PubMed] [Google Scholar]
- Hahn S. A., Schutte M., Hoque A. T., Moskaluk C. A., da Costa L. T., Rozenblum E., Weinstein C. L., Fischer A., Yeo C. J., Hruban R. H. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996 Jan 19;271(5247):350–353. doi: 10.1126/science.271.5247.350. [DOI] [PubMed] [Google Scholar]
- Henry I., Grandjouan S., Couillin P., Barichard F., Huerre-Jeanpierre C., Glaser T., Philip T., Lenoir G., Chaussain J. L., Junien C. Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma. Proc Natl Acad Sci U S A. 1989 May;86(9):3247–3251. doi: 10.1073/pnas.86.9.3247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirano Y., Fujita K., Suzuki K., Ushiyama T., Ohtawara Y., Tsuda F. Telomerase activity as an indicator of potentially malignant adrenal tumors. Cancer. 1998 Aug 15;83(4):772–776. [PubMed] [Google Scholar]
- Iida A., Blake K., Tunny T., Klemm S., Stowasser M., Hayward N., Gordon R., Nakamura Y., Imai T. Allelic losses on chromosome band 11q13 in aldosterone-producing adrenal tumors. Genes Chromosomes Cancer. 1995 Jan;12(1):73–75. doi: 10.1002/gcc.2870120114. [DOI] [PubMed] [Google Scholar]
- Ilvesmäki V., Kahri A. I., Miettinen P. J., Voutilainen R. Insulin-like growth factors (IGFs) and their receptors in adrenal tumors: high IGF-II expression in functional adrenocortical carcinomas. J Clin Endocrinol Metab. 1993 Sep;77(3):852–858. doi: 10.1210/jcem.77.3.8370710. [DOI] [PubMed] [Google Scholar]
- Kamb A., Gruis N. A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S. V., Stockert E., Day R. S., 3rd, Johnson B. E., Skolnick M. H. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994 Apr 15;264(5157):436–440. doi: 10.1126/science.8153634. [DOI] [PubMed] [Google Scholar]
- Kananen K., Markkula M., Mikola M., Rainio E. M., McNeilly A., Huhtaniemi I. Gonadectomy permits adrenocortical tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene: evidence for negative autoregulation of the inhibin alpha-subunit gene. Mol Endocrinol. 1996 Dec;10(12):1667–1677. doi: 10.1210/mend.10.12.8961275. [DOI] [PubMed] [Google Scholar]
- Karakousis C. P., Rao U., Moore R. Adrenal adenocarcinomas: histologic grading and survival. J Surg Oncol. 1985 Jun;29(2):105–111. doi: 10.1002/jso.2930290208. [DOI] [PubMed] [Google Scholar]
- Kingsley D. M. The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 1994 Jan;8(2):133–146. doi: 10.1101/gad.8.2.133. [DOI] [PubMed] [Google Scholar]
- Kjellman M., Kallioniemi O. P., Karhu R., Hög A., Farnebo L. O., Auer G., Larsson C., Bäckdahl M. Genetic aberrations in adrenocortical tumors detected using comparative genomic hybridization correlate with tumor size and malignancy. Cancer Res. 1996 Sep 15;56(18):4219–4223. [PubMed] [Google Scholar]
- Li F. P., Fraumeni J. F., Jr Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 1969 Oct;71(4):747–752. doi: 10.7326/0003-4819-71-4-747. [DOI] [PubMed] [Google Scholar]
- Macoska J. A., Micale M. A., Sakr W. A., Benson P. D., Wolman S. R. Extensive genetic alterations in prostate cancer revealed by dual PCR and FISH analysis. Genes Chromosomes Cancer. 1993 Oct;8(2):88–97. doi: 10.1002/gcc.2870080205. [DOI] [PubMed] [Google Scholar]
- Matzuk M. M., Finegold M. J., Mather J. P., Krummen L., Lu H., Bradley A. Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8817–8821. doi: 10.1073/pnas.91.19.8817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McBride O. W., Merry D., Givol D. The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13). Proc Natl Acad Sci U S A. 1986 Jan;83(1):130–134. doi: 10.1073/pnas.83.1.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McNicol A. M., Nolan C. E., Struthers A. J., Farquharson M. A., Hermans J., Haak H. R. Expression of p53 in adrenocortical tumours: clinicopathological correlations. J Pathol. 1997 Feb;181(2):146–152. doi: 10.1002/(SICI)1096-9896(199702)181:2<146::AID-PATH744>3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
- Murphy D. S., Hoare S. F., Going J. J., Mallon E. E., George W. D., Kaye S. B., Brown R., Black D. M., Keith W. N. Characterization of extensive genetic alterations in ductal carcinoma in situ by fluorescence in situ hybridization and molecular analysis. J Natl Cancer Inst. 1995 Nov 15;87(22):1694–1704. doi: 10.1093/jnci/87.22.1694. [DOI] [PubMed] [Google Scholar]
- Ohgaki H., Kleihues P., Heitz P. U. p53 mutations in sporadic adrenocortical tumors. Int J Cancer. 1993 May 28;54(3):408–410. doi: 10.1002/ijc.2910540310. [DOI] [PubMed] [Google Scholar]
- Poddighe P. J., Ramaekers F. C., Hopman A. H. Interphase cytogenetics of tumours. J Pathol. 1992 Mar;166(3):215–224. doi: 10.1002/path.1711660303. [DOI] [PubMed] [Google Scholar]
- Prinz R. A., Brooks M. H., Churchill R., Graner J. L., Lawrence A. M., Paloyan E., Sparagana M. Incidental asymptomatic adrenal masses detected by computed tomographic scanning. Is operation required? JAMA. 1982 Aug 13;248(6):701–704. [PubMed] [Google Scholar]
- Ried T. Interphase cytogenetics and its role in molecular diagnostics of solid tumors. Am J Pathol. 1998 Feb;152(2):325–327. [PMC free article] [PubMed] [Google Scholar]
- Rosenberg C., Della-Rosa V. A., Latronico A. C., Mendonça B. B., Vianna-Morgante A. M. Selection of adrenal tumor cells in culture demonstrated by interphase cytogenetics. Cancer Genet Cytogenet. 1995 Jan;79(1):36–40. doi: 10.1016/0165-4608(94)00079-q. [DOI] [PubMed] [Google Scholar]
- Sasano N., Takezawa Y., Sato H., Horikawa N. Micro-angiography of normal and pathologic human adrenals in prenatal and aging course. Tohoku J Exp Med. 1971 Jun;104(2):129–141. doi: 10.1620/tjem.104.129. [DOI] [PubMed] [Google Scholar]
- Shackney S. E., Smith C. A., Miller B. W., Burholt D. R., Murtha K., Giles H. R., Ketterer D. M., Pollice A. A. Model for the genetic evolution of human solid tumors. Cancer Res. 1989 Jun 15;49(12):3344–3354. [PubMed] [Google Scholar]
- Skogseid B., Larsson C., Lindgren P. G., Kvanta E., Rastad J., Theodorsson E., Wide L., Wilander E., Oberg K. Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 1992 Jul;75(1):76–81. doi: 10.1210/jcem.75.1.1352309. [DOI] [PubMed] [Google Scholar]
- Sneige N., Sahin A., Dinh M., El-Naggar A. Interphase cytogenetics in mammographically detected breast lesions. Hum Pathol. 1996 Apr;27(4):330–335. doi: 10.1016/s0046-8177(96)90104-5. [DOI] [PubMed] [Google Scholar]
- Srivastava S., Zou Z. Q., Pirollo K., Blattner W., Chang E. H. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990 Dec 20;348(6303):747–749. doi: 10.1038/348747a0. [DOI] [PubMed] [Google Scholar]
- Thompson N. W., Cheung P. S. Diagnosis and treatment of functioning and nonfunctioning adrenocortical neoplasms including incidentalomas. Surg Clin North Am. 1987 Apr;67(2):423–436. doi: 10.1016/s0039-6109(16)44193-9. [DOI] [PubMed] [Google Scholar]
- Visscher D. W., Wallis T. L., Crissman J. D. Evaluation of chromosome aneuploidy in tissue sections of preinvasive breast carcinomas using interphase cytogenetics. Cancer. 1996 Jan 15;77(2):315–320. doi: 10.1002/(SICI)1097-0142(19960115)77:2<315::AID-CNCR14>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
- Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
- Weksberg R., Teshima I., Williams B. R., Greenberg C. R., Pueschel S. M., Chernos J. E., Fowlow S. B., Hoyme E., Anderson I. J., Whiteman D. A. Molecular characterization of cytogenetic alterations associated with the Beckwith-Wiedemann syndrome (BWS) phenotype refines the localization and suggests the gene for BWS is imprinted. Hum Mol Genet. 1993 May;2(5):549–556. doi: 10.1093/hmg/2.5.549. [DOI] [PubMed] [Google Scholar]
- Yano T., Linehan M., Anglard P., Lerman M. I., Daniel L. N., Stein C. A., Robertson C. N., LaRocca R., Zbar B. Genetic changes in human adrenocortical carcinomas. J Natl Cancer Inst. 1989 Apr 5;81(7):518–523. doi: 10.1093/jnci/81.7.518. [DOI] [PubMed] [Google Scholar]
- van Slooten H., Schaberg A., Smeenk D., Moolenaar A. J. Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer. 1985 Feb 15;55(4):766–773. doi: 10.1002/1097-0142(19850215)55:4<766::aid-cncr2820550414>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]