Evaluation of microsatellite instability in women with epithelial ovarian cancer

Caliman,Leonardo  Pandolfi; Carvalho Tavares,Rubens   Lene; Barbosa Piedade,Josiane; Silvano Couto de Assis,Ana   Carolina; de Jesus Dias da Cunha,Karen; da Conceição Braga,Letícia; Silva,Luciana   Maria; da Silva Filho,Agnaldo   Lopes

doi:10.3892/ol.2012.776

Evaluation of microsatellite instability in women with epithelial ovarian cancer

Authors:
- Leonardo Pandolfi Caliman
- Rubens Lene Carvalho Tavares
- Josiane Barbosa Piedade
- Ana Carolina Silvano Couto de Assis
- Karen de Jesus Dias da Cunha
- Letícia da Conceição Braga
- Luciana Maria Silva
- Agnaldo Lopes da Silva Filho
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Affiliations: Department of Obstetrics and Gynecology, Faculty of Medicine, Federal University of Minas Gerais (UFMG), 30130-100, Brazil, Research and Development Center, Ezequiel Dias Foundation, 30510-010, Belo Horizonte, Minas Gerais, Brazil
Published online on: June 27, 2012 https://doi.org/10.3892/ol.2012.776
Pages: 556-560

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Abstract

The function of microsatellite instability (MSI) and the optimal panel of markers for epithelial ovarian cancer (EOC) are not well established. This study aimed to use the National Cancer Institute (NCI) markers BAT25, BAT26, D2S123, D5S346 and D17S250 to evaluate MSI in patients with ovarian serous cystadenocarcinoma, compared with ovarian serous cystadenoma and normal ovaries. A total of 37 patients were divided into three groups, as follows: cystadenocarcinoma (n=13), cystadenoma (n=10) and normal ovaries (n=14). DNA was extracted with TRIzol and quantified by spectrophotometry. MSI was evaluated by polymerase chain reaction (PCR), and classified as high (MSI-H), low (MSI-L) or stable (MSS). FIGO staging was I/II in 23.1% and III/IV in 76.9% of the cystadenocarcinoma group. Polymorphisms were found using at least one marker in 32 women, and were observed with D2S123 (83.7%), D17S250 (81.1%), D5S346 (72.9%), BAT25 (21.6%) and BAT26 (16.2%) markers. In the cystadenocarcinoma group, BAT25, BAT26, D2S123, D5S346 and D17S250 markers were positive in 30.8, 76.9, 53.8, 69.2 and 69.2% of patients, respectively. The same markers were positive in 30, 50, 40, 60 and 30% of the cystadenoma group, and 50, 71.4, 71.4, 64.3 and 63.3% in the normal ovary group, respectively. MSI-H was present in 84.6, 60 and 78.6% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. MSI-L was detected in 0, 30 and 7.1%, and MSS was identified in 15.4, 10 and 14.3% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. The frequency of MSI in both benign epithelial ovarian neoplasms and in normal ovaries was high, as well as in EOC, with no statistically significant difference between the groups. This suggests that MSI may arise as a consequence of the ovulatory process, and not solely as a feature of malignant ovarian tumors.

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1	Silva-Filho AL, Carmo GA, Athayde GR, Assis ME, Almeida RC, Leal RH, Lamaita RM, Santos-Júnior JL and Castro e Silva JG: Safe fertility-preserving management in gynecological malignancies. Arch Gynecol Obstet. 275:321–330. 2007. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar
3	Dorigo O and Berek JS: Personalizing CA125 levels for ovarian cancer screening. Cancer Prev Res (Phila). 4:1356–1359. 2011. View Article : Google Scholar : PubMed/NCBI
4	Brewer MA, Johnson K, Follen M, Gershenson D and Bast R Jr: Prevention of ovarian cancer: intraepithelial neoplasia. Clin Cancer Res. 9:20–30. 2003.PubMed/NCBI
5	Roett MA and Evans P: Ovarian cancer: an overview. Am Fam Physician. 80:609–616. 2009.
6	Feeley KM and Wells M: Precursor lesions of ovarian epithelial malignancy. Histopathology. 38:87–95. 2001. View Article : Google Scholar : PubMed/NCBI
7	Dubeau L: The cell of origin of ovarian epithelial tumours. Lancet Oncol. 9:1191–1197. 2008. View Article : Google Scholar : PubMed/NCBI
8	Berek JS, Chalas E, Edelson M, Moore DH, Burke WM, Cliby WA and Berchuck A; Society of Gynecologic Oncologists Clinical Practice Committee. Prophylactic and risk-reducing bilateral salpingo-oophorectomy: recommendations based on risk of ovarian cancer. Obstet Gynecol. 116:733–743. 2010. View Article : Google Scholar : PubMed/NCBI
9	Pal T, Permuth-Wey J and Sellers TA: A review of the clinical relevance of mismatch-repair deficiency in ovarian cancer. Cancer. 113:733–742. 2008. View Article : Google Scholar : PubMed/NCBI
10	Sidransky D: Emerging molecular markers of cancer. Nat Rev Cancer. 2:210–219. 2002. View Article : Google Scholar
11	Sood AK, Holmes R, Hendrix MJ and Buller RE: Application of the National Cancer Institute international criteria for determination of microsatellite instability in ovarian cancer. Cancer Res. 61:4371–4374. 2001.PubMed/NCBI
12	Singer G, Kallinowski T, Hartmann A, Dietmaier W, Wild PJ, Schraml P, Sauter G, Mihatsch MJ and Moch H: Different types of microsatellite instability in ovarian carcinoma. Int J Cancer. 112:643–646. 2004. View Article : Google Scholar : PubMed/NCBI
13	Fathalla MF: Incessant ovulation-a factor in ovarian neoplasia? Lancet. 2:1631971. View Article : Google Scholar : PubMed/NCBI
14	Hennessy BT, Coleman RL and Markman M: Ovarian cancer. Lancet. 374:1371–1382. 2009. View Article : Google Scholar : PubMed/NCBI
15	Massey A, Offman J, Macpherson P and Karran P: DNA mismatch repair and acquired cisplatin resistance in E. coli and human ovarian carcinoma cells. DNA Repair (Amst). 2:73–89. 2003. View Article : Google Scholar : PubMed/NCBI
16	Crijnen TE, Janssen-Heijnen ML, Gelderblom H, Morreau J, Nooij MA, Kenter GG and Vasen HF: Survival of patients with ovarian cancer due to a mismatch repair defect. Fam Cancer. 4:301–305. 2005. View Article : Google Scholar : PubMed/NCBI
17	Lawes DA, SenGupta S and Boulos PB: The clinical importance and prognostic implications of microsatellite instability in sporadic cancer. Eur J Surg Oncol. 29:201–212. 2003. View Article : Google Scholar : PubMed/NCBI
18	Vaughn CP, Lyon E and Samowitz WZ: Confirmation of single exon deletions in MLH1 and MSH2 using quantitative polymerase chain reaction. J Mol Diagn. 10:355–360. 2008. View Article : Google Scholar : PubMed/NCBI
19	Lu Y, Liu XS, Wang YX, Song HY and Zhong N: Study of microsatellite instability in epithelial ovarian tumors. Beijing Da Xue Xue Bao. 38:62–65. 2006.PubMed/NCBI
20	Yoon BS, Kim YT, Kim JH, Kim SW, Nam EJ, Cho NH, Kim JW and Kim S: Clinical significance of microsatellite instability in sporadic epithelial ovarian tumors. Yonsei Med J. 49:272–278. 2008. View Article : Google Scholar : PubMed/NCBI
21	Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, Redston M and Gallinger S: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 342:69–77. 2000. View Article : Google Scholar : PubMed/NCBI
22	Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M and Gallinger S: Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 349:247–257. 2003. View Article : Google Scholar : PubMed/NCBI
23	Sakamoto-Hojo ET and Balajee AS: Targeting poly (ADP) ribose polymerase I (PARP-1) and PARP-1 interacting proteins for cancer treatment. Anticancer Agents Med Chem. 8:402–416. 2008. View Article : Google Scholar : PubMed/NCBI
24	Murphy MA and Wentzensen N: Frequency of mismatch repair deficiency in ovarian cancer: a systematic review. International Journal of Cancer. 129:1914–1922. 2011. View Article : Google Scholar : PubMed/NCBI
25	Guppy AE, Nathan PD and Rustin GJ: Epithelial ovarian cancer: a review of current management. Clin Oncol (R Coll Radiol). 17:399–411. 2005. View Article : Google Scholar : PubMed/NCBI