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British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Apr;77(8):1337–1342. doi: 10.1038/bjc.1998.223

Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected by interphase cytogenetics: basic findings and clinical aspects.

N Zojer 1, M Fiegl 1, L Müllauer 1, A Chott 1, S Roka 1, J Ackermann 1, M Raderer 1, H Kaufmann 1, A Reiner 1, H Huber 1, J Drach 1
PMCID: PMC2150163  PMID: 9579843

Abstract

To date, cytogenetic studies on pancreatic carcinoma are rare, and little is known about the frequency of cytogenetic aberrations in primary carcinomas compared with metastatic tumour cells. We therefore evaluated the frequency of chromosomal aberrations in 12 primary pancreatic carcinomas and in effusion specimens from 25 patients with pancreatic cancer by using interphase fluorescence in situ hybridization (FISH) and a panel of four centromeric probes. Hyperdiploidy and chromosomal imbalances, predominantly affecting chromosome 8, were a constant finding in metastatic effusion cells, whereas concordant gain of chromosomes or relative loss of chromosome 18 characterized primary pancreatic carcinomas. The potential role of oncogenes located on chromosome 8 for pancreatic cancer progression was further investigated by double-hybridization studies of aneuploid effusion cells with a probe to 8q24 (MYC) and a centromeric probe to chromosome 8, which demonstrated amplification of the MYC oncogene in two of ten cases (20%). Finally, a potential application of basic findings in the clinical setting was tested by searching for micrometastatic cells in effusions from pancreatic cancer patients primarily negative by FISH. Two-colour FISH in combination with extensive screening (>10,000 nuclei) seems to be a useful tool to unequivocally identify micrometastatic cells by demonstrating hyperdiploidy and intranuclear chromosomal heterogeneity.

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  1. Bardi G., Aman P., Johansson B., Pandis N., Mandahl N., Bak-Jensen E., Björkman A., Sjögren H. O., Andrén-Sandberg A., Mitelman F. Cytogenetic characterization of a periampullary adenocarcinoma of the pancreas, its liver metastasis, and a cell line established from the metastasis and a cell line established from the metastasis in a patient with Gardner's syndrome. Cancer Genet Cytogenet. 1994 Aug;76(1):29–32. doi: 10.1016/0165-4608(94)90065-5. [DOI] [PubMed] [Google Scholar]
  2. Bardi G., Johansson B., Pandis N., Mandahl N., Bak-Jensen E., Andrén-Sandberg A., Mitelman F., Heim S. Karyotypic abnormalities in tumours of the pancreas. Br J Cancer. 1993 May;67(5):1106–1112. doi: 10.1038/bjc.1993.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bugalho M. J., Roque L., Sobrinho L. G., Hoog A., Nunes J. F., Almeida J. M., Leitão C. N., Santos J. R., Pereira M. C., Santos M. A. Calcitonin-producing insulinoma: clinical, immunocytochemical and cytogenetical study. Clin Endocrinol (Oxf) 1994 Aug;41(2):257–260. doi: 10.1111/j.1365-2265.1994.tb02539.x. [DOI] [PubMed] [Google Scholar]
  4. Bullerdiek J., Bartnitzke S., Kahrs E., Schloot W. Further evidence for nonrandom chromosome changes in carcinoma cells--a report of 28 cases. Cancer Genet Cytogenet. 1985 Mar 1;16(1):33–43. doi: 10.1016/0165-4608(85)90075-5. [DOI] [PubMed] [Google Scholar]
  5. Casalone R., Meriggi F., Forni E., Pasquali F. Cytogenetic findings in a case of anaplastic carcinoma of the pancreas. Cancer Genet Cytogenet. 1987 Dec;29(2):253–259. doi: 10.1016/0165-4608(87)90236-6. [DOI] [PubMed] [Google Scholar]
  6. Cote R. J., Rosen P. P., Lesser M. L., Old L. J., Osborne M. P. Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. J Clin Oncol. 1991 Oct;9(10):1749–1756. doi: 10.1200/JCO.1991.9.10.1749. [DOI] [PubMed] [Google Scholar]
  7. Danner D. B., Hruban R. H., Pitt H. A., Hayashi R., Griffin C. A., Perlman E. J. Primitive neuroectodermal tumor arising in the pancreas. Mod Pathol. 1994 Feb;7(2):200–204. [PubMed] [Google Scholar]
  8. Drach J., Angerler J., Schuster J., Rothermundt C., Thalhammer R., Haas O. A., Jäger U., Fiegl M., Geissler K., Ludwig H. Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance. Blood. 1995 Nov 15;86(10):3915–3921. [PubMed] [Google Scholar]
  9. Dutrillaux B., Gerbault-Seureau M., Remvikos Y., Zafrani B., Prieur M. Breast cancer genetic evolution: I. Data from cytogenetics and DNA content. Breast Cancer Res Treat. 1991 Nov;19(3):245–255. doi: 10.1007/BF01961161. [DOI] [PubMed] [Google Scholar]
  10. Fiegl M., Tueni C., Schenk T., Jakesz R., Gnant M., Reiner A., Rudas M., Pirc-Danoewinata H., Marosi C., Huber H. Interphase cytogenetics reveals a high incidence of aneuploidy and intra-tumour heterogeneity in breast cancer. Br J Cancer. 1995 Jul;72(1):51–55. doi: 10.1038/bjc.1995.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fukushige S., Waldman F. M., Kimura M., Abe T., Furukawa T., Sunamura M., Kobari M., Horii A. Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma. Genes Chromosomes Cancer. 1997 Jul;19(3):161–169. doi: 10.1002/(sici)1098-2264(199707)19:3<161::aid-gcc5>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  12. Gorunova L., Johansson B., Dawiskiba S., Andrén-Sandberg A., Jin Y., Mandahl N., Heim S., Mitelman F. Massive cytogenetic heterogeneity in a pancreatic carcinoma: fifty-four karyotypically unrelated clones. Genes Chromosomes Cancer. 1995 Dec;14(4):259–266. doi: 10.1002/gcc.2870140404. [DOI] [PubMed] [Google Scholar]
  13. Grant L. D., Lauwers G. Y., Meloni A. M., Stone J. F., Betz J. L., Vogel S., Sandberg A. A. Unbalanced chromosomal translocation, der(17)t(13;17)(q14;p11) in a solid and cystic papillary epithelial neoplasm of the pancreas. Am J Surg Pathol. 1996 Mar;20(3):339–345. doi: 10.1097/00000478-199603000-00011. [DOI] [PubMed] [Google Scholar]
  14. Griffin C. A., Hruban R. H., Long P. P., Morsberger L. A., Douna-Issa F., Yeo C. J. Chromosome abnormalities in pancreatic adenocarcinoma. Genes Chromosomes Cancer. 1994 Feb;9(2):93–100. doi: 10.1002/gcc.2870090204. [DOI] [PubMed] [Google Scholar]
  15. Griffin C. A., Hruban R. H., Morsberger L. A., Ellingham T., Long P. P., Jaffee E. M., Hauda K. M., Bohlander S. K., Yeo C. J. Consistent chromosome abnormalities in adenocarcinoma of the pancreas. Cancer Res. 1995 Jun 1;55(11):2394–2399. [PubMed] [Google Scholar]
  16. 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]
  17. Jenkins R. B., Qian J., Lieber M. M., Bostwick D. G. Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization. Cancer Res. 1997 Feb 1;57(3):524–531. [PubMed] [Google Scholar]
  18. Johansson B., Bardi G., Heim S., Mandahl N., Mertens F., Bak-Jensen E., Andrén-Sandberg A., Mitelman F. Nonrandom chromosomal rearrangements in pancreatic carcinomas. Cancer. 1992 Apr 1;69(7):1674–1681. doi: 10.1002/1097-0142(19920401)69:7<1674::aid-cncr2820690706>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  19. Juhl H., Stritzel M., Wroblewski A., Henne-Bruns D., Kremer B., Schmiegel W., Neumaier M., Wagener C., Schreiber H. W., Kalthoff H. Immunocytological detection of micrometastatic cells: comparative evaluation of findings in the peritoneal cavity and the bone marrow of gastric, colorectal and pancreatic cancer patients. Int J Cancer. 1994 May 1;57(3):330–335. doi: 10.1002/ijc.2910570307. [DOI] [PubMed] [Google Scholar]
  20. Lindemann F., Schlimok G., Dirschedl P., Witte J., Riethmüller G. Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients. Lancet. 1992 Sep 19;340(8821):685–689. doi: 10.1016/0140-6736(92)92230-d. [DOI] [PubMed] [Google Scholar]
  21. Litle V. R., Warren R. S., Moore D., 2nd, Pallavicini M. G. Molecular cytogenetic analysis of cytokeratin 20-labeled cells in primary tumors and bone marrow aspirates from colorectal carcinoma patients. Cancer. 1997 May 1;79(9):1664–1670. [PubMed] [Google Scholar]
  22. Long P. P., Hruban R. H., Lo R., Yeo C. J., Morsberger L. A., Griffin C. A. Chromosome analysis of nine endocrine neoplasms of the pancreas. Cancer Genet Cytogenet. 1994 Oct;77(1):55–59. doi: 10.1016/0165-4608(94)90149-x. [DOI] [PubMed] [Google Scholar]
  23. Ott G., Kalla J., Ott M. M., Schryen B., Katzenberger T., Müller J. G., Müller-Hermelink H. K. Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones. Blood. 1997 Feb 15;89(4):1421–1429. [PubMed] [Google Scholar]
  24. Sakorafas G. H., Lazaris A., Tsiotou A. G., Koullias G., Glinatsis M. T., Golematis B. C. Oncogenes in cancer of the pancreas. Eur J Surg Oncol. 1995 Jun;21(3):251–253. doi: 10.1016/s0748-7983(95)91294-0. [DOI] [PubMed] [Google Scholar]
  25. Scappaticci S., Brandi M. L., Capra E., Cortinovis M., Maraschio P., Fraccaro M. Cytogenetics of multiple endocrine neoplasia syndrome. II. Chromosome abnormalities in an insulinoma and a glucagonoma from two subjects with MEN1. Cancer Genet Cytogenet. 1992 Oct 1;63(1):17–21. doi: 10.1016/0165-4608(92)90057-f. [DOI] [PubMed] [Google Scholar]
  26. Schenk T., Ackermann J., Brunner C., Schenk P., Zojer N., Roka S., Drach J. Detection of chromosomal aneuploidy by interphase fluorescence in situ hybridization in bronchoscopically gained cells from lung cancer patients. Chest. 1997 Jun;111(6):1691–1696. doi: 10.1378/chest.111.6.1691. [DOI] [PubMed] [Google Scholar]
  27. Soder A. I., Hopman A. H., Ramaekers F. C., Conradt C., Bosch F. X. Distinct nonrandom patterns of chromosomal aberrations in the progression of squamous cell carcinomas of the head and neck. Cancer Res. 1995 Nov 1;55(21):5030–5037. [PubMed] [Google Scholar]
  28. Solinas-Toldo S., Wallrapp C., Müller-Pillasch F., Bentz M., Gress T., Lichter P. Mapping of chromosomal imbalances in pancreatic carcinoma by comparative genomic hybridization. Cancer Res. 1996 Aug 15;56(16):3803–3807. [PubMed] [Google Scholar]
  29. Teyssier J. R. Nonrandom chromosomal changes in human solid tumors: application of an improved culture method. J Natl Cancer Inst. 1987 Dec;79(6):1189–1198. [PubMed] [Google Scholar]
  30. Wiley J., Posekany K., Riley R., Holbrook T., Silverman J., Joshi V., Bowyer S. Cytogenetic and flow cytometric analysis of a pancreatoblastoma. Cancer Genet Cytogenet. 1995 Feb;79(2):115–118. doi: 10.1016/0165-4608(94)00117-t. [DOI] [PubMed] [Google Scholar]
  31. Yamada H., Sakamoto H., Taira M., Nishimura S., Shimosato Y., Terada M., Sugimura T. Amplifications of both c-Ki-ras with a point mutation and c-myc in a primary pancreatic cancer and its metastatic tumors in lymph nodes. Jpn J Cancer Res. 1986 Apr;77(4):370–375. [PubMed] [Google Scholar]
  32. Zojer N., Fiegl M., Angerler J., Müllauer L., Gsur A., Roka S., Pecherstorfer M., Huber H., Drach J. Interphase fluorescence in situ hybridization improves the detection of malignant cells in effusions from breast cancer patients. Br J Cancer. 1997;75(3):403–407. doi: 10.1038/bjc.1997.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. van der Riet-Fox M. F., Retief A. E., van Niekerk W. A. Chromosome changes in 17 human neoplasms studied with banding. Cancer. 1979 Dec;44(6):2108–2119. doi: 10.1002/1097-0142(197912)44:6<2108::aid-cncr2820440622>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]

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