Endometrial cancer and microsatellite instability status

• Authors: Daiva Kanopiene , Jolanta Vidugiriene , Konstantinas Povilas Valuckas , Giedre Smailyte , Saule Uleckiene , Jeff Bacher
• Languages of publication: EN

Abstracts

EN

Microsatellite instability (MSI) is an important
factor in the development of various cancers as an identifier
of a defective DNA mismatch repair system. The objective
of our study was to define the association between
microsatellite instability status and traditional clinicopathologic
characteristics of endometrioid type adenocarcinoma.
Material and methods: MSI status of endometrial
cancer was examined by employing the Promega
MSI Analysis System. This system uses 5 mononucleotide
markers to identify MSI in tumour and normal tissue DNA
(BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide
markers (Penta C and Penta D) for specimen
identification. In this study, we investigated MSI status
in 109 endometrial carcinomas. Results and conclusions:
One hundred (92%) of 109 endometrial cancers showed
endometrioid type histology and only 9 (8%) non-endometrioid
type. MSI-high was found in 17% (17/100)
of endometrioid type adenocarcinomas, in 0% (0/9) of
non-endometrioid carcinomas. Selected clinicopathologic
parameters for endometrioid type adenocarcinomas were
compared to the MSI status which was separated into two
groups – MSI-high and MSI stable. The results showed
that MSI-high status was related to clinicopathologic
parameters such as deep myometrial invasion and higher
histologic grade in endometrioid type adenocarcinomas.

Keywords

EN

Endometrial cancer; Clinicopathologic parameters; Microsatellite instability

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2014
• Volume: 10
• Issue: 1

Dates

online

11 - 11 - 2014

received

13 - 11 - 2013

accepted

29 - 8 - 2014

Contributors

author

Daiva Kanopiene

• Out Patient Clinic, National
  cancer institute, Santariskiu 1, LT-08660, Vilnius, Lithuania

author

Jolanta Vidugiriene

• Promega Corporation, Madison WI, USA

author

Konstantinas Povilas Valuckas

• Radiotherapy and Drug Therapy
  Center, National cancer institute, Santariskiu 1, LT-08660, Vilnius,
  Lithuania

author

Giedre Smailyte

• Scientific Research Center, National cancer institute,
  Santariskiu 1, LT-08660, Vilnius, Lithuania

author

Saule Uleckiene

• Scientific Research Center, National cancer institute,
  Santariskiu 1, LT-08660, Vilnius, Lithuania

author

Jeff Bacher

• Promega Corporation, Madison WI, USA

References

• [1] Weiderpass E, Labreche F. Malignant tumors of the femalereproductive system. Saf Health Work 2012; 3:166-180[Crossref]
• [2] Bray F, Loos AH, Oostindier M, Weiderpass E. Geographic andtemporal variations in cancer of the corpus uteri: incidence andmortality in pre- and postmenopausal women in Europe. Int JCancer 2005; 117:123-131[Crossref]
• [3] Sherman ME. Theories of endometrial carcinogenesis: amultidisciplinary approach. Mod Pathol 2000; 13:295-308[Crossref]
• [4] Basil JB, Goodfellow PJ, Rader JS, Mutch DG, Herzog TJ.Clinical significance of microsatellite instability in endometrialcarcinoma. Cancer 2000; 89:1758-1764[Crossref]
• [5] Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, LongacreTA, et al. Uterine papillary serous and clear cell carcinomaspredict for poorer survival compared to grade 3 endometrioidcorpus cancers. Br J Cancer 2006; 94:642-646
• [6] Liu FS. Molecular carcinogenesis of endometrial cancer. TaiwanJ Obstet Gynecol 2007; 46:26-32[Crossref]
• [7] Tinelli A, Mezzolla V, Leo G, Pisano M, Storelli F, Alemanno G,et al. Microsatellite instability (MSI) as genomic markers inendometrial cancer: toward scientific evidences. Mini Rev MedChem 2010; 10:1356-1365[Crossref]
• [8] Weigelt B, Banerjee S. Molecular targets and targetedtherapeutics in endometrial cancer. Curr Opin Oncol 2012;24:554-563[Crossref][WoS]
• [9] Ellegren H. Microsatellites: simple sequences with complexevolution. Nat Rev Genet 2004; 5:435-445[Crossref]
• [10] Li YC, Korol AB, Fahima T, Nevo E. Microsatellites withingenes: structure, function, and evolution. Mol Biol Evol 2004;21:991-1007[Crossref]
• [11] Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, EshlemanJR, Burt RW, et al. A National Cancer Institute Workshop onMicrosatellite Instability for cancer detection and familialpredisposition: development of international criteria for thedetermination of microsatellite instability in colorectal cancer.Cancer Res 1998; 58:5248-5257
• [12] Meyer LA, Broaddus RR, Lu KH. Endometrial cancer and Lynchsyndrome: clinical and pathologic considerations. CancerControl 2009; 16:14-22
• [13] Zaanan A, Meunier K, Sangar F, Flejou JF, Praz F. Microsatelliteinstability in colorectal cancer: from molecular oncogenicmechanisms to clinical implications. Cell Oncol (Dordr) 2011;34:155-176[WoS][Crossref]
• [14] Karamurzin Y, Zeng Z, Stadler ZK, Zhang L, Ouansafi I,Al-Ahmadie HA, et al. Unusual DNA mismatch repair-deficienttumors in Lynch syndrome: a report of new cases and review ofthe literature. Hum Pathol 2012; 43:1677-1687[Crossref][WoS]
• [15] Leenen CH, van Lier MG, van Doorn HC, van Leerdam ME, KooiSG, de Waard J, et al. Prospective evaluation of molecularscreening for Lynch syndrome in patients with endometrialcancer </= 70 years. Gynecol Oncol 2012; 125:414-420[WoS][Crossref]
• [16] van Lier MG, Wagner A, van Leerdam ME, Biermann K, KuipersEJ, Steyerberg EW, et al. A review on the molecular diagnosticsof Lynch syndrome: a central role for the pathology laboratory. JCell Mol Med 2010; 14:181-197[Crossref][WoS]
• [17] Schneider R, Schneider C, Kloor M, Furst A, Moslein G. Lynchsyndrome: clinical, pathological, and genetic insights.Langenbecks Arch Surg 2012; 397:513-525[Crossref][WoS]
• [18] Bartley AN, Luthra R, Saraiya DS, Urbauer DL, BroaddusRR. Identification of cancer patients with Lynch syndrome:clinically significant discordances and problems intissue-based mismatch repair testing. Cancer Prev Res (Phila)2012; 5:320-327[Crossref][WoS]
• [19] Popat S, Hubner R, Houlston RS. Systematic review of microsatelliteinstability and colorectal cancer prognosis. J Clin Oncol2005; 23:609-618[Crossref]
• [20] Boland CR, Goel A. Microsatellite instability in colorectalcancer. Gastroenterology 2010; 138:2073-87 e3[Crossref][WoS]
• [21] Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, FrenchAJ, Goldberg RM, et al. Tumor microsatellite-instabilitystatus as a predictor of benefit from fluorouracil-basedadjuvant chemotherapy for colon cancer. N Engl J Med 2003;349:247-257[Crossref]
• [22] Bertagnolli MM, Niedzwiecki D, Compton CC, Hahn HP, HallM, Damas B, et al. Microsatellite instability predicts improvedresponse to adjuvant therapy with irinotecan, fluorouracil,and leucovorin in stage III colon cancer: Cancer and LeukemiaGroup B Protocol 89803. J Clin Oncol 2009; 27:1814-1821[WoS][Crossref]
• [23] MacDonald ND, Salvesen HB, Ryan A, Iversen OE, Akslen LA,Jacobs IJ. Frequency and prognostic impact of microsatelliteinstability in a large population-based study of endometrialcarcinomas. Cancer Res 2000; 60:1750-1752
• [24] Maxwell GL, Risinger JI, Alvarez AA, Barrett JC, Berchuck A.Favorable survival associated with microsatellite instabilityin endometrioid endometrial cancers. Obstet Gynecol 2001;97:417-422
• [25] Goodfellow PJ, Buttin BM, Herzog TJ, Rader JS, Gibb RK,Swisher E, et al. Prevalence of defective DNA mismatch repairand MSH6 mutation in an unselected series of endometrialcancers. Proc Natl Acad Sci U S A 2003; 100:5908-5913[Crossref]
• [26] An HJ, Kim KI, Kim JY, Shim JY, Kang H, Kim TH, et al.Microsatellite instability in endometrioid type endometrialadenocarcinoma is associated with poor prognostic indicators.Am J Surg Pathol 2007; 31:846-8453[Crossref]
• [27] Black D, Soslow RA, Levine DA, Tornos C, Chen SC, HummerAJ, et al. Clinicopathologic significance of defective DNAmismatch repair in endometrial carcinoma. J Clin Oncol 2006;24:1745-1753[Crossref]
• [28] Baldinu P, Cossu A, Manca A, Satta MP, Pisano M, Casula M, etal. Microsatellite instability and mutation analysis of candidategenes in unselected sardinian patients with endometrialcarcinoma. Cancer 2002; 94:3157-3168[Crossref]
• [29] Hirasawa A, Aoki D, Inoue J, Imoto I, Susumu N, Sugano K,et al. Unfavorable prognostic factors associated with highfrequency of microsatellite instability and comparative genomichybridization analysis in endometrial cancer. Clin Cancer Res2003; 9:5675-5682
• [30] Buttin BM, Powell MA, Mutch DG, Rader JS, Herzog TJ,Gibb RK, et al. Increased risk for hereditary nonpolyposiscolorectal cancer-associated synchronous and metachronousmalignancies in patients with microsatellite instability-positiveendometrial carcinoma lacking MLH1 promoter methylation.Clin Cancer Res 2004; 10:481-490[Crossref]
• [31] Steinbakk A, Malpica A, Slewa A, Gudlaugsson E, JanssenEA, Arends M, et al. High frequency microsatellite instabilityhas a prognostic value in endometrial endometrioidadenocarcinoma, but only in FIGO stage 1 cases. Cell Oncol(Dordr) 2011; 34:457-465[WoS][Crossref]
• [32] Zighelboim I, Goodfellow PJ, Gao F, Gibb RK, Powell MA, RaderJS, et al. Microsatellite instability and epigenetic inactivation ofMLH1 and outcome of patients with endometrial carcinomas ofthe endometrioid type. J Clin Oncol 2007; 25:2042-2048[Crossref]
• [33] Murphy KM, Zhang S, Geiger T, Hafez MJ, Bacher J, Berg KD, etal. Comparison of the microsatellite instability analysis systemand the Bethesda panel for the determination of microsatelliteinstability in colorectal cancers. J Mol Diagn 2006; 8:305-311[Crossref]
• [34] Wong YF, Cheung TH, Lo KW, Yim SF, Chan LK, Buhard O, et al.Detection of microsatellite instability in endometrial cancer:advantages of a panel of five mononucleotide repeats over theNational Cancer Institute panel of markers. Carcinogenesis2006; 27:951-955[Crossref]

Identifiers

DOI

10.1515/med-2015-0005