난소 상피암에서 현미부수체 불안정성 분석 = Analysis of Microsatellite Instability in Ovarian Epithelial Cancer

다국어 초록 (Multilingual Abstract)

Background : The aim of this study was to clarify the incidence and role of microsatellite instability
(MSI) in sporadic ovarian epithelial cancers (OEC). We investigated the MSI status and
mismatch repair (MMR) protein expression in OEC. Methods : MSI was examined by fluorescence-
based polymerase chain reaction using five NCI panel markers (BAT25, BAT26, D2S123,
D5S346 and D17S250) in 46 cases of OEC. Immunohistochemistry (IHC) for hMLH1 and
hMSH2 was performed. Results : Seven cases (15.2%) exhibited high-frequency MSI (MSIH),
one exhibited low-frequency MSI (MSI-L), and the remaining 38 demonstrated microsatellite
stability (MSS). MSI-H in OEC was not associated with histologic grade, FIGO stage, tumor
size, mitoses or histologic type. Loss of expression of either hMLH1 or hMSH2 was observed
in 4 of the 7 (59.3%) MSI-H cases, whereas 4 of the 39 (10.3%) MSI-L or MSS tumors revealed
loss of expression of MMR proteins. The sensitivity and specificity of immunohistochemistry
for hMLH1 and hMSH2 were 57.1% and 89.7%. Conclusions : Our data suggest that a genetic
defect in the MMR system might play a role in the carcinogenesis of a minor subset of sporadic
OEC however, immunohistochemical testing for hMLH1 and hMSH2 cannot accurately
determine microsatellite instability status in OEC.

참고문헌 (Reference)

1 Chiaravalli AM, "The role of histologicalinvestigation in prognostic evaluation of advanced gastric cancer analysis of histological structure and molecular changes compared with invasive pattern and stage" 439 : 158-169, 2001

2 Shih I, "Ovarian tumorigenesis:a proposed model basedon morphological and molecular genetic analysis" 164 : 1511-1518, 2004

3 Catasus L, "Molecular genetic alterationsin endometrioid carcinomas of the ovary:Similar frequency of betacateninabnormalities but lower rate of microsatellite instability andPTEN alterations than in uterine endometrioid carcinomas" 35 : 1360-1368, 2004

4 Dellas A, "Molecular and clinicopathologicalanalysis of ovarian carcinomas with and without microsatellite instability" 24 : 361-369, 2004

5 Pal T, "Mismatch repair gene expression defectscontribute to microsatellite instability in ovarian carcinoma" 100 : 2485-2486, 2004

6 Geisler JP, "Mismatch repair gene expression defects contribute to microsatelliteinstability in ovarian carcinoma" 98 : 2199-2206, 2003

7 Ueda H, "Microsatellitestatus and immunohistochemical features of ovarian clearcellcarcinoma" 25 : 2785-2788, 2005

8 Allen HJ, "Microsatelliteinstability in ovarian and other pelvic carcinomas" 117 : 163-166, 2000

9 Cha HJ, "Microsatelliteinstability in colorectal carcinomas" 35 : 111-114, 2001

10 Arzimanoglou II, "Microsatelliteinstability differences between familial and sporadic ovarian cancers" 17 : 1799-1804, 1996

11 Gras E, "Microsatellite instability, MLH-1 promoter hypermethylation and frameshift mutations at codingmononucleotide repeat microsatellites in ovarian tumors" 92 : 2829-2836, 2001

12 King BL, "Microsatellite instability inovarian neoplasms" 72 : 376-382, 1995

13 Thibodeau SN, "Microsatellite instability in cancerof the proximal colon" 260 : 816-9, 1993

14 Codegoni AM, "Microsatellite instability andframeshift mutations in genes involved in cell cycle progression orapoptosis in ovarian cancer" 11 : 297-301, 1999

15 Liu J, "Microsatellite instability andexpression of hMLH1 and hMSH2 proteins in ovarian endometrioidcancer" 17 : 75-80, 2004

16 Fujita M, "Microsatellite instability andalterations in the hMSH2 gene in human ovarian cancer" 64 : 361-366, 1995

17 Cai KQ, "Microsatellite instability andalteration of the expression of hMLH1 and hMSH2 in ovarian clearcell carcinoma" 35 : 552-559, 2004

18 Haas CJ, "Microsatellite analysis in serous tumors of the ovary" 18 : 158-162, 1999

19 Hardman RA, "Involvement of mammalianMLH1 in the apoptotic response to peroxide-induced oxidative stress" 61 : 1392-1397, 2001

20 Marcus VA, "Immunohistochemistry forhMLH1 and hMSH2:A practical test for DNA mismatch repair-deficienttumors" 23 : 1248-1255, 1999

21 Lanza G, "Immunohistochemicalpattern of MLH1/MSH2 expression is related toclinical and pathological features in colorectal adenocarcinomas withmicrosatellite instability" 15 : 741-749, 2002

22 Rosen DG, "Immunohistochemical stainingof hMLH1 and hMSH2 reflects microsatellite instability status in ovariancarcinoma" 19 : 1414-1420, 2006

23 Silverberg SG, "Histopathologic grading of ovarian carcinoma:a reviewand proposal" 19 : 7-15, 2000

24 Maxwell GL, "Favorablesurvival associated with microsatellite instability in endometrioidendometrial cancers" 97 : 417-422, 2001

25 Velasco A, "Differential expression of themismatch repair gene hMSH2 in malignant prostate tissue is associatedwith cancer recurrence" 94 : 690-699, 2002

26 Singer G, "Different types of microsatelliteinstability in ovarian carcinoma" 112 : 643-646, 2004

27 Ohwada M, "DNA replication errors are frequentin mucinous cystadenocarcinoma of the ovary" 117 : 61-65, 2000

28 Cawkwell L, "Choice of management strategyfor colorectal cancer based on a diagnostic immunohistochemicaltest for defective mismatch repair" 45 : 409-415, 1999

29 Sood AK, "Application of the nationalcancer institute international criteria for determination of microsatelliteinstability in ovarian cancer" 61 : 4371-4374, 2001

30 Boland CR, "A national cancer instituteworkshop on microsatellite instability for cancer detection andfamilial predisposition:Development of international criteria for thedetermination of microsatellite instability in colorectal cancer" 58 : 5248-5257, 1998