Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 10, October, p. 1417–1424

doi: 10.17219/acem/70861

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Studies on selected molecular factors in endometrial cancers

Anna Markowska1,A,D,F, Monika Szarszewska2,A,B,C, Jakub Żurawski3,B,C, Stefan Sajdak4,B, Paweł Knapp5,B, Anna Gryboś6,B, Anita Olejek7,B, Wiesława Bednarek8,B, Andrzej Roszak9,B, Marcin Jóźwik10,B, Andrzej Marszałek11,B,C, Violetta Filas11,B,C, Katarzyna Wójcik-Krowiranda12,B, Radosław Mądry2,B, Janina Markowska2,A,E,F, Rafał Sozański13,B

1 Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poland

2 Department of Gynecological Oncology, Poznan University of Medical Sciences, Poland

3 Department of Biology and Environmental Protections, Division of Immunobiochemistry, Poznan University of Medical Sciences, Poland

4 Department of Gynecological Surgery, Poznan University of Medical Sciences, Poland

5 Department of Gynecology and Gynecologic Oncology, Medical University of Bialystok, Poland

6 Department of Gynecology and Obstetrics, Faculty of Health Science, Wroclaw Medical University, Poland

7 Department of Gynecology, Obstetrics and Oncologic Gynecology, Medical University of Silesia, Bytom, Poland

8 Chair and Clinic of Gynecological Oncology, Medical University of Lublin, Poland

9 Department of Electroradiology, Poznan University of Medical Science, Greater Poland Cancer Centre, Poland

10 Chair and Department of Gynecology, Gynecologic Endocrinology and Obstetrics, University of Warmia and Mazury in Olsztyn, Poland

11 Department of Tumor Pathology and Prophylaxis, Poznan University of Medical Sciences, Greater Poland Cancer Center, Poland

12 Department of Gynecological Oncology, Medical University of Lodz, Poland

13 1st Department and Clinic of Gynaecology and Obstetrics, Wroclaw Medical University, Poland

Abstract

Background. Endometrial carcinomas (EC) differ in etiology, clinical course and prognosis.
Objectives. This multi-center study aimed at a closer recognition of molecular factors linked to heterogeneity of EC by evaluating estrogen and progesterone receptors, proteins dependent on MMR genes, proteins linked to poor prognosis and metastases, and mutations in BRCA1.
Material and Methods. Using sections of paraffin-embedded preparations, in 115 patients with EC type I and 31 with EC type II, expression of ERα, ERβ1, PR, MLH1, and MSH2 proteins, as well as ARID1A, c-MET and BRCA1, was estimated by immunohistochemistry using specific antibodies.
Results. Expression of ERβ1 was augmented in EC type II, in poorly differentiated cancers and with growing clinical advancement. An augmented expression of ERα was noted in well-differentiated EC and at lower clinical stage. An increased expression of PR and decreased of MLH1 were detected in type I EC. The expression of ARID1A and c-MET proteins showed no differences between the types of EC, stages of clinical advancement or grading. In 51.6% patients with type II EC, a loss of BRCA1 expression was disclosed; in this group of cancers a decreased expression of ERα was noted.
Conclusion. An augmented expression of ERβ1 was linked to type II EC. A higher expression of ERα in EC cancers was associated with a lower histopathological grade. A decreased expression of MLH1 protein was estimated in EC type I. Type II EC may be connected to BRCA1 mutation.

Key words

endometrial cancer, BRCA1, estrogen receptors, MMR, ARID1A

References (36)

  1. Globocan 2012 Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact-sheets-population.asp. Accessed on January 17, 2015.
  2. Ferlay J, Soerjomataram I, Ervik M, et al. Globocan 2012 v. 1.0. http://globocan.iarc.fr. Accessed on January 16, 2015.
  3. Bokhman JV. Two pathogenic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10–17.
  4. Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: Have they different risk factors? J Clin Oncol. 2013;31(20):2607–2618.
  5. Colombo N, Creutzberg C, Amant F, et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, treatment and follow-up. Int J Gynecol Cancer. 2016;25:1–24.
  6. Reid-Nicholson M, Iyengar P, Hummer AJ, Linkov I, Asher M, Soslow RA. Immunophenotypic diversity of endometrial adenocarcinomas: Implications for differential diagnosis. Mod Pathol. 2006;19(8):1091–1100.
  7. Colombo N, Preti E, Landoni F, Carinelli S, Colombo A. Endometrial cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi33–vi38.
  8. Cossio SL, Koehler-Santos P, Pessini SA, et al. Clinical and histomolecular endometrial tumor characterization of patients at-risk for Lynch syndrome in south of Brazil. Fam Cancer. 2010;9(2):131–139.
  9. Huang M, Djordjevic B, Yates MS, et al. Molecular pathogenesis of endometrial cancers in patients with Lynch syndrome. Cancer. 2013;119(16):3027–3033.
  10. Fader AN, Santin AD, Gehrig PA. Early stage uterine serous carcinoma: Management updates and genomic advances. Gynecol Oncol. 2013;129(1):244–250.
  11. Attias-Geva Z, Bentov I, Kidron D, et al. p53 regulates insulin-like growth factor-I receptor gene expression in uterine serous carcinoma and predicts responsiveness to an insulin-like growth factor-I receptor-directed targeted therapy. Eur J Cancer. 2012;48(10):1570–1580.
  12. Kreizman-Shefer H, Pricop J, Goldman S, Elmalah I, Shalev E. Distribution of estrogen and progesterone receptors isoforms in endometrial cancer. Diagn Pathol. 2014;9:77.
  13. Togami S, Sasajima Y, Oi T, et al. Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma. Cancer Sci. 2012;103(5):926–932.
  14. Sho T, Hachisuga T, Nguyen TT, et al. Expression of estrogen receptor-α as a prognostic factor in patients with uterine serous carcinoma. Int J Gynecol Cancer. 2014;24(1):102–106.
  15. Park JY, Nam JH, Kim YT, et al. Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients. Virchows Arch. 2013;462(3):289–296.
  16. Sagae S, Susumu N, Viswanathan AN, Aoki D, Backes FJ, Provencher DM. Gynecologic Cancer InterGroup (GCIG) consensus review for uterine serous carcinoma. Int J Gynecol Cancer. 2014;24(9 Suppl 3):S83–S89.
  17. Hampel H, Frankel W, Panescu J, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006;66(15):7810–7817.
  18. Bischoff J, Ignatov A, Semczuk A, et al. hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases. Clin Exp Metastasis. 2012;29(8):889–900.
  19. Brinton LA, Felix AS, McMeekin DS, et al. Etiologic heterogeneity in endometrial cancer: Evidence from a Gynecologic Oncology Group trial. Gynecol Oncol. 2013;129(2):277–284.
  20. Hayes MP, Ellenson LH. Molecular alterations in uterine serous carcinoma. Gynecol Oncol. 2010;116(2):286–289.
  21. Takeda T, Banno K, Okawa R, et al. ARID1A gene mutation in ovarian and endometrial cancers (Review). Oncol Rep. 2015;35(2):607–613.
  22. Bishop EA, Lengyel ER, Yamada SD, Montag A, Temkin SM. The expression of hepatocyte growth factor (HGF) and c-MET in uterine serous carcinoma. Gynecol Oncol. 2011;121(1):218–223.
  23. Bruchim I, Amichay K, Kidron D, et al. BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma. Int J Gynecol Cancer. 2010;20(7):1148–1153.
  24. Rafii S, Dawson P, Williams S, Pascoe JS, Nevin JE, Sundar S. Is uterine serous carcinoma a part of hereditary breast cancer syndrome? J Clin Oncol. 2013;31 (suppl; abstr 5587). doi: 10.1200/jco.2013.31.15_suppl.5587
  25. Zhao C, Dahlman-Wright K, Gustafsson JA. Estrogen receptor beta: An overview and update. Nucl Recept Signal. 2008;6:e003.
  26. Hapangama DK, Kamal AM, Bulmer JN. Estrogen receptor β: The guardian of the endometrium. Hum Reprod Update. 2015;21(2):174–193.
  27. Chakravarty D, Srinivasan R, Ghosh S, Gopalan S, Rajwanshi A, Majumdar S. Estrogen receptor beta1 and the beta2/betacx isoforms in non-neoplastic endometrium and in endometrioid carcinoma. Int J Gynecol Cancer. 2007;17(4):905–913.
  28. Zhu C, Luo J, Shi H, Xie X, Ding Z. Expression of tubulin, p53, ki67, receptors for estrogen, and progesterone in endometrial cancer. Eur J Gynaecol Oncol. 2009;30(5):514–517.
  29. Lindor NM. Lynch syndrome 101 (years, that is). Am Soc Clin Oncol Educ Book. 2014:27–32. doi: 10.14694/EdBook_AM.2014.34.27
  30. Berends MJW, Hollema H, Wu Y, et al. MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non-hereditary endometrial hyperplasia and cancer. Int J Cancer. 2001;92:398–403.
  31. Bosse T, ter Haar NT, Seeber LM, v Diest PJ, Hes J, Vasen HFA. Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer. Mod Pathol. 2013;26:1525–1535.
  32. Li M, Xin X, Wu T, Hua T, Wang H, Wang H. Stromal cells of endometrial carcinoma promotes proliferation of epithelial cells through the HGF/c-MET/Akt signaling pathway. Tumour Biol. 2015;36(8):6239–6248.
  33. Zhuang XP, Jin WW, Teng XD, Yuan ZZ, Lin QQ, Xu ST. c-MET and RON expression levels in endometrial adenocarcinoma tissue and their relationship with prognosis. Eur J Gynaecol Oncol. 2015;36(3):255–259.
  34. Li M, Xin X, Wu T, Hua T, Wang H. HGF and c-MET in pathogenesis of endometrial carcinoma. Front Biosci. 2015;20:635–643.
  35. Felix AS, Edwards RP, Stone RA, et al. Associations between hepatocyte growth factor, c-MET, and basic fibroblast growth factor and survival in endometrial cancer patients. Br J Cancer. 2012;106(12):2004–2009.
  36. Fan S, Ma YX, Wang C, et al. Role of direct interaction in BRCA1 inhibition of estrogen receptor activity. Oncogene. 2001;20(1):77–87.
© Wroclaw Medical University