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Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2014

01.10.2014 | Original Article – Cancer Research

Estrogen receptor promoter methylation predicts survival in low-grade ovarian carcinoma patients

verfasst von: Verena Kirn, Rong Shi, Sabine Heublein, Julia Knabl, Margit Guenthner-Biller, Ulrich Andergassen, Claudius Fridrich, Wolfram Malter, Jan Harder, Klaus Friese, Doris Mayr, Udo Jeschke

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2014

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Abstract

Purpose

Ovarian carcinoma is the third most common gynecological cancer and only short recurrence-free survival and overall survival times are archived. The role of the estrogen receptor expression is well studied in breast cancer and breast cancer cell lines. Patients with positive estrogen receptor expression have a lower risk for recurrence and a better overall survival. Previous studies have shown that ESR1 methylation influences ovarian cancer development and might thus play a role regarding prognosis of ovarian carcinoma.

Methods

A total of 75 patients were identified that were treated for ovarian carcinoma by debulking surgery and adjuvant standard chemotherapy. Isolation and bisulfite treatment of genomic DNA from serial sections of surgically resected ovarian carcinoma tissue was performed using commercially available kits. For the detection of methylated ESR1 promoter sequences, real-time methylation-specific PCR was used.

Results

Promoter methylation did not show a correlation between clinical–pathological data for all patients. However, within the subgroup of low-grade ovarian carcinoma patients and patients with an ovarian tumor of low malignant potential methylation of the ESR1 promoter inversely correlated with survival (p = 0.031).

Conclusions

Although small numbers of ovarian carcinoma patients were analyzed, methylation status might be useful as a prognostic marker within the subgroup of low-grade ovarian carcinoma patients. Further studies should investigate a larger cohort and also address the use of demethylation agents with respect to improve patient’s prognosis in this subgroup of ovarian carcinoma patients.
Literatur
Zurück zum Zitat Eads CA, Lord RV, Kurumboor SK, Wickramasinghe K, Skinner ML, Long TI, Peters JH, DeMeester TR, Danenberg KD, Danenberg PV, Laird PW, Skinner KA (2000) Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Cancer Res 60:5021–5026PubMed Eads CA, Lord RV, Kurumboor SK, Wickramasinghe K, Skinner ML, Long TI, Peters JH, DeMeester TR, Danenberg KD, Danenberg PV, Laird PW, Skinner KA (2000) Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Cancer Res 60:5021–5026PubMed
Zurück zum Zitat Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61:3225–3229PubMed Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61:3225–3229PubMed
Zurück zum Zitat Harder J, Engelstaedter V, Usadel H, Lassmann S, Werner M, Baier P, Otto F, Varbanova M, Schaeffner E, Olschewski M, Blum HE, Opitz OG (2009) CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer 100(2):360–365. doi:10.1038/sj.bjc.6604859 PubMedCrossRefPubMedCentral Harder J, Engelstaedter V, Usadel H, Lassmann S, Werner M, Baier P, Otto F, Varbanova M, Schaeffner E, Olschewski M, Blum HE, Opitz OG (2009) CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer 100(2):360–365. doi:10.​1038/​sj.​bjc.​6604859 PubMedCrossRefPubMedCentral
Zurück zum Zitat Houshdaran S, Hawley S, Palmer C, Campan M, Olsen MN, Ventura AP, Knudsen BS, Drescher CW, Urban ND, Brown PO, Laird PW (2012) DNA Methylation profiles of ovarian epithelial carcinoma tumors and cell lines. PLoS ONE 5(2):e9359. doi:10.1371/journal.pone.0009359 CrossRef Houshdaran S, Hawley S, Palmer C, Campan M, Olsen MN, Ventura AP, Knudsen BS, Drescher CW, Urban ND, Brown PO, Laird PW (2012) DNA Methylation profiles of ovarian epithelial carcinoma tumors and cell lines. PLoS ONE 5(2):e9359. doi:10.​1371/​journal.​pone.​0009359 CrossRef
Zurück zum Zitat Huang YW, Jansen RA, Fabbri E, Potter D, Liyanarachchi S, Chan MW, Liu JC, Crijns AP, Brown R, Nephew KP, van der Zee AG, Cohn DE, Yan PS, Huang TH, Lin HJ (2009) Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncol Rep 22(4):853–861PubMedPubMedCentral Huang YW, Jansen RA, Fabbri E, Potter D, Liyanarachchi S, Chan MW, Liu JC, Crijns AP, Brown R, Nephew KP, van der Zee AG, Cohn DE, Yan PS, Huang TH, Lin HJ (2009) Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncol Rep 22(4):853–861PubMedPubMedCentral
Zurück zum Zitat Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7(4):536–540PubMedCrossRef Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7(4):536–540PubMedCrossRef
Zurück zum Zitat Issa JP, Zehnbauer BA, Civin CI, Collector MI, Sharkis SJ, Davidson NE, Kaufmann SH, Baylin SB (1996) The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. Cancer Res 56(5):973–977PubMed Issa JP, Zehnbauer BA, Civin CI, Collector MI, Sharkis SJ, Davidson NE, Kaufmann SH, Baylin SB (1996) The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. Cancer Res 56(5):973–977PubMed
Zurück zum Zitat Lapidus RG, Ferguson AT, Ottaviano YL, Parl FE, Smith HS, Weitzman SA, Baylin SB, Issa JP, Davidson NE (1996) Methylation of estrogen and progesterone receptor gene 5′ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res 2(5):805–810PubMed Lapidus RG, Ferguson AT, Ottaviano YL, Parl FE, Smith HS, Weitzman SA, Baylin SB, Issa JP, Davidson NE (1996) Methylation of estrogen and progesterone receptor gene 5′ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res 2(5):805–810PubMed
Zurück zum Zitat Lapidus RG, Nass SJ, Davidson NE (1998a) The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mammary Gland Biol Neoplasia 3(1):85–94PubMedCrossRef Lapidus RG, Nass SJ, Davidson NE (1998a) The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mammary Gland Biol Neoplasia 3(1):85–94PubMedCrossRef
Zurück zum Zitat Lapidus RG, Nass SJ, Butash KA, Parl FF, Weitzman SA, Graff JG, Herman JG, Davidson NE (1998b) Mapping of ER gene CpG island methylation-specific polymerase chain reaction. Cancer Res 58(12):2515–2519PubMed Lapidus RG, Nass SJ, Butash KA, Parl FF, Weitzman SA, Graff JG, Herman JG, Davidson NE (1998b) Mapping of ER gene CpG island methylation-specific polymerase chain reaction. Cancer Res 58(12):2515–2519PubMed
Zurück zum Zitat Lenhard M, Lennerova T, Heublein S, Ditsch N, Himsl I, Mayr D, Friese K, Jeschke U (2012) Steroid hormone receptor expression in ovarian cancer: progesterone receptor B as prognostic marker for patient survival. BMC Cancer 12:553PubMedCrossRefPubMedCentral Lenhard M, Lennerova T, Heublein S, Ditsch N, Himsl I, Mayr D, Friese K, Jeschke U (2012) Steroid hormone receptor expression in ovarian cancer: progesterone receptor B as prognostic marker for patient survival. BMC Cancer 12:553PubMedCrossRefPubMedCentral
Zurück zum Zitat McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and IV ovarian cancer. New Eng J Med 334:1–6PubMedCrossRef McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and IV ovarian cancer. New Eng J Med 334:1–6PubMedCrossRef
Zurück zum Zitat Montavon C, Glos BS, Warton K, Barton CA, Statham AL, Scurry JP, Tabor B, Nguyen TV, Qu W, Samimi G, Hacker NF, Sutherland RL, Clark SJ, O‘Brien PM (2012) Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer. Gynecol Oncol 124:582–588. doi:10.1016/j.ygyno.2011.11.026 PubMedCrossRef Montavon C, Glos BS, Warton K, Barton CA, Statham AL, Scurry JP, Tabor B, Nguyen TV, Qu W, Samimi G, Hacker NF, Sutherland RL, Clark SJ, O‘Brien PM (2012) Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer. Gynecol Oncol 124:582–588. doi:10.​1016/​j.​ygyno.​2011.​11.​026 PubMedCrossRef
Zurück zum Zitat Newcomb PA, Longnecker MP, Storer BE, Mittendorf R, Baron J, Clapp RW, Bogdan G, Willett WC (1995) Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women. Am J Epidemiol 142(8):788–795PubMed Newcomb PA, Longnecker MP, Storer BE, Mittendorf R, Baron J, Clapp RW, Bogdan G, Willett WC (1995) Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women. Am J Epidemiol 142(8):788–795PubMed
Zurück zum Zitat O’Doherty AM, Church SW, Russel SE, Nelson J, Hickey I (2002) Methylation status of oestrogen receptor alpha gene promoter sequence in human ovarian epithelial cell lines. Br J Cancer 86(2):282–284PubMedCrossRefPubMedCentral O’Doherty AM, Church SW, Russel SE, Nelson J, Hickey I (2002) Methylation status of oestrogen receptor alpha gene promoter sequence in human ovarian epithelial cell lines. Br J Cancer 86(2):282–284PubMedCrossRefPubMedCentral
Zurück zum Zitat Shaw D, Clamp A, Jayson GC (2013) Angiogenesis as a target for the treatment of ovarian cancer. Curr Opin Oncol 25(5):558–565PubMedCrossRef Shaw D, Clamp A, Jayson GC (2013) Angiogenesis as a target for the treatment of ovarian cancer. Curr Opin Oncol 25(5):558–565PubMedCrossRef
Zurück zum Zitat Shi IM, Chen L, Wang C, Gu J, Davidson B, Cope L, Kurman RJ, Xuan J, Wang TL (2010) Distinct DNA methylation profiles in ovarian serous neoplasms and their implications in ovarian carcinogenesis. Am J Obstet Gynecol 203(6):584.e1–584.e22. doi:10.1016/j.ajog.2010.08.003 Shi IM, Chen L, Wang C, Gu J, Davidson B, Cope L, Kurman RJ, Xuan J, Wang TL (2010) Distinct DNA methylation profiles in ovarian serous neoplasms and their implications in ovarian carcinogenesis. Am J Obstet Gynecol 203(6):584.e1–584.e22. doi:10.​1016/​j.​ajog.​2010.​08.​003
Zurück zum Zitat Teodoridis JM, Hall J, Marsh S, Kannall HD, Smyth C, Curto J, Siddiqui N, Gabra H, McLeod HL, Strathdee G, Brown R (2005) CpG Island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res 65(19):8961–8967PubMedCrossRef Teodoridis JM, Hall J, Marsh S, Kannall HD, Smyth C, Curto J, Siddiqui N, Gabra H, McLeod HL, Strathdee G, Brown R (2005) CpG Island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res 65(19):8961–8967PubMedCrossRef
Zurück zum Zitat Wei SH, Balch C, Paik HH, Kim YS, Baldwin RL, Liyanarchchi S, Li L, Wang Z, Wan JC, Davuluri RV, Karlan BY, Gifford G, Brown R, Kim S, Huang TH, Nephew KP (2006) Prognostik DNA methylation biomarkers in ovarian cancer. Clin Cancer Res 12(9):2788–2794PubMedCrossRef Wei SH, Balch C, Paik HH, Kim YS, Baldwin RL, Liyanarchchi S, Li L, Wang Z, Wan JC, Davuluri RV, Karlan BY, Gifford G, Brown R, Kim S, Huang TH, Nephew KP (2006) Prognostik DNA methylation biomarkers in ovarian cancer. Clin Cancer Res 12(9):2788–2794PubMedCrossRef
Zurück zum Zitat Wiley A, Katsaros D, Chen H, Rigault de la Longrais IA, Beeghly A, Puopolo M, Singal R, Zhang Y, Amoako A, Zelterman D, Yu H (2006) Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential. Cancer 107(2):299–308PubMedCrossRef Wiley A, Katsaros D, Chen H, Rigault de la Longrais IA, Beeghly A, Puopolo M, Singal R, Zhang Y, Amoako A, Zelterman D, Yu H (2006) Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential. Cancer 107(2):299–308PubMedCrossRef
Zurück zum Zitat Yang HJ, Liu VWS, Wang Y, Tsang PC, Ngan HY (2006) Differential DNA methylation profiles in gynecological cancers and correlation with clinic-pathological data. BMC Cancer 6:212PubMedCrossRefPubMedCentral Yang HJ, Liu VWS, Wang Y, Tsang PC, Ngan HY (2006) Differential DNA methylation profiles in gynecological cancers and correlation with clinic-pathological data. BMC Cancer 6:212PubMedCrossRefPubMedCentral
Zurück zum Zitat Yap OWS, Bhat G, Liu L, Tollefsbol TO (2009) Epigenetic modifications of the estrogen receptor β gene in epithelial ovarian cancer cells. Anticancer Res 29(1):139–144PubMedPubMedCentral Yap OWS, Bhat G, Liu L, Tollefsbol TO (2009) Epigenetic modifications of the estrogen receptor β gene in epithelial ovarian cancer cells. Anticancer Res 29(1):139–144PubMedPubMedCentral
Metadaten
Titel
Estrogen receptor promoter methylation predicts survival in low-grade ovarian carcinoma patients
verfasst von
Verena Kirn
Rong Shi
Sabine Heublein
Julia Knabl
Margit Guenthner-Biller
Ulrich Andergassen
Claudius Fridrich
Wolfram Malter
Jan Harder
Klaus Friese
Doris Mayr
Udo Jeschke
Publikationsdatum
01.10.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2014
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1729-9

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