title: Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum.
abstract: Lynch syndrome (HNPCC) is a dominantly inherited disorder characterized by germline defects in DNA mismatch repair (MMR) genes and the development of a variety of cancers, predominantly colorectal and endometrial. We present a 44-year-old woman who was shown to carry the truncating MSH2 gene mutation that had previously been identified in her family. Recently, she had been diagnosed with an undifferentiated carcinoma of the thyroid and an adenoma of her coecum. Although the thyroid carcinoma was not MSI-high (1 out of 5 microsatellites instable), it did show complete loss of immunohistochemical expression for the MSH2 protein, suggesting that this tumour was not coincidental. Although the risks for some tumour types, including breast cancer, soft tissue sarcoma and prostate cancer, are not significantly increased in Lynch syndrome, MMR deficiency in the presence of a corresponding germline defect has been demonstrated in incidental cases of a growing range of tumour types, which is reviewed in this paper. Interestingly, the MSH2-associated tumour spectrum appears to be wider than that of MLH1 and generally the risk for most extra-colonic cancers appears to be higher for MSH2 than for MLH1 mutation carriers. Together with a previously reported case, our findings show that anaplastic thyroid carcinoma can develop in the setting of Lynch syndrome. Uncommon Lynch syndrome-associated tumour types might be useful in the genetic analysis of a Lynch syndrome suspected family if samples from typical Lynch syndrome tumours are unavailable.
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. r.p.stulp@medgen.umcg.nl
authors.forename: Rein P
authors.initials: RP
authors.lastname: Stulp
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Herkert
authors.forename: Arend
authors.initials: A
authors.lastname: Karrenbeld
authors.forename: Bart
authors.initials: B
authors.lastname: Mol
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Vos
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Sijmons
references.citation: J Natl Cancer Inst. 2006 Mar 1;98(5):358-61
references.pmid: 16507833
references.citation: Hum Pathol. 2006 Nov;37(11):1498-502
references.pmid: 16996571
references.citation: J Med Genet. 2007 Jul;44(7):e83
references.pmid: 17601929
references.citation: Hum Mol Genet. 1997 Jan;6(1):105-10
references.pmid: 9002677
references.citation: Am J Hum Genet. 2004 May;74(5):954-64
references.pmid: 15077197
references.citation: Cancer. 2007 Jun 1;109(11):2349-56
references.pmid: 17440981
references.citation: Cancer Res. 1999 Jan 15;59(2):294-7
references.pmid: 9927034
references.citation: Histopathology. 2003 Sep;43(3):297-9
references.pmid: 12940783
references.citation: Gastroenterology. 1996 Apr;110(4):1020-7
references.pmid: 8612988
references.citation: Am J Hum Genet. 2004 Jun;74(6):1262-9
references.pmid: 15098177
references.citation: Cancer Res. 2001 Jun 1;61(11):4541-4
references.pmid: 11389087
references.citation: Am J Gastroenterol. 2005 Aug;100(8):1886-91
references.pmid: 16144131
references.citation: Cancer Res. 1999 Jan 15;59(2):290-3
references.pmid: 9927033
references.citation: Breast Cancer Res Treat. 1999 Jan;53(1):87-91
references.pmid: 10206076
references.citation: Fam Cancer. 2001;1(2):101-5
references.pmid: 14574005
references.citation: Nat Genet. 1997 Oct;17(2):135-6
references.pmid: 9326924
references.citation: Hum Mutat. 2007 Nov;28(11):1084-90
references.pmid: 17557300
references.citation: Eur J Hum Genet. 2006 May;14(5):561-6
references.pmid: 16418736
references.citation: Am J Med Genet A. 2005 Dec 1;139A(2):96-105; discussion 96
references.pmid: 16283678
references.citation: J Med Genet. 2002 May;39(5):335-9
references.pmid: 12011152
references.citation: Eur J Hum Genet. 2008 Jan;16(1):62-72
references.pmid: 17851451
references.citation: Gastroenterology. 2004 Jul;127(1):17-25
references.pmid: 15236168
references.citation: Fam Cancer. 2008;7(3):191-8
references.pmid: 18049911
references.citation: Clin Cancer Res. 2005 Jul 1;11(13):4689-93
references.pmid: 16000562
references.citation: J Natl Cancer Inst. 2004 Feb 18;96(4):261-8
references.pmid: 14970275
references.citation: Hum Genet. 1999 Nov;105(5):437-41
references.pmid: 10598809
references.citation: Fam Cancer. 2004;3(2):123-7
references.pmid: 15340263
references.citation: J Clin Oncol. 2004 Nov 15;22(22):4486-94
references.pmid: 15483016
references.citation: Int J Cancer. 1999 Apr 12;81(2):214-8
references.pmid: 10188721
references.citation: Gastroenterology. 2004 Feb;126(2):576-85
references.pmid: 14762794
references.citation: Mod Pathol. 2004 Aug;17(8):981-9
references.pmid: 15143336
references.citation: Cancer Res. 2002 Jan 15;62(2):359-62
references.pmid: 11809679
references.citation: Gastroenterology. 2005 Aug;129(2):415-21
references.pmid: 16083698
references.citation: Fam Cancer. 2007;6(1):141-5
references.pmid: 17051350
references.citation: Obstet Gynecol. 2007 Aug;110(2 Pt 2):543-5
references.pmid: 17666659
references.citation: Am J Gastroenterol. 2006 Jan;101(1):193-6
references.pmid: 16405554
references.citation: J Med Genet. 2005 Jun;42(6):491-6
references.pmid: 15937084
references.citation: Am J Med Genet A. 2003 Aug 30;121A(2):159-62
references.pmid: 12910497
references.citation: Cancer. 1996 May 1;77(9):1836-43
references.pmid: 8646682
references.citation: N Engl J Med. 1995 Mar 30;332(13):839-47
references.pmid: 7661930
references.citation: Nat Clin Pract Oncol. 2007 Feb;4(2):130-4
references.pmid: 17259933
references.citation: Am J Hum Genet. 2003 Jan;72(1):213-6
references.pmid: 12549480
references.citation: Gut. 2006 Dec;55(12):1781-8
references.pmid: 16636019
references.citation: Genes Chromosomes Cancer. 2000 Dec;29(4):353-5
references.pmid: 11066081
references.citation: Oncogene. 2000 Mar 23;19(13):1719-23
references.pmid: 10763829
references.citation: Cancer Genet Cytogenet. 2004 Dec;155(2):149-51
references.pmid: 15571801
references.citation: Genes Chromosomes Cancer. 1997 Apr;18(4):269-78
references.pmid: 9087566
references.citation: Am J Med Genet A. 2006 Feb 1;140(3):195-9
references.pmid: 16372347
references.citation: Am J Hum Genet. 2002 Jan;70(1):26-37
references.pmid: 11709755
references.citation: J Clin Oncol. 2001 Oct 15;19(20):4074-80
references.pmid: 11600610
references.citation: Hum Pathol. 2005 Dec;36(12):1322-6
references.pmid: 16311127
references.citation: Genes Chromosomes Cancer. 2008 Apr;47(4):326-32
references.pmid: 18181177