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Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

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Pathology & Oncology Research

Abstract

To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ER-alpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.

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References

  1. Nephew KP, Choi CM, Polek TC, et al: Expression of fos and jun proto-oncogenes in benign versus malignant human uterine tissue. Gynecol Oncol 76: 388–396, 2000

    Article  PubMed  CAS  Google Scholar 

  2. Shiozawa T, Miyamoto T, Kashima H, et al: Estrogen-induced proliferation of normal endometrial glandular cells is initiated by transcriptional activation of cyclin D1 via binding of c-jun to an AP-1 sequence. Oncogene 23: 8603–8610, 2004

    Article  PubMed  CAS  Google Scholar 

  3. Udou T, Hachisuga T, Tsujioka H, Kawarabayashi T: The role of c-jun protein in proliferation and apoptosis of the endometrium throughout the menstrual cycle. Gynecol Obstet Invest 57: 121–126, 2004

    Article  PubMed  CAS  Google Scholar 

  4. Yamashita S, Takayanagi A, Shimizu N: Temporal and cell-type specific expression of c-fos and c-jun protooncogenes in the mouse uterus after estrogen stimulation. Endocrinology 137: 5468–5475, 1996

    Article  PubMed  CAS  Google Scholar 

  5. Subramaniam M, Harris SA, Rasmussen K, Speisberg TC: Rapid down-regulation of c-jun protooncogene transcription by progesterone in the avian oviduct. Endocrinology 133: 2049–2054, 1993

    Article  PubMed  CAS  Google Scholar 

  6. Webb DK, Moulton BC, Khan SA: Estrogen induced expression of the c-jun proto-oncogene in the immature and mature rat uterus. Biochem Biophys Res Commun 168: 721–726, 1990

    Article  PubMed  CAS  Google Scholar 

  7. Morishita S, Niwa K, Ichigo S, et al: Overexpressions of c-fos/jun mRNA and their oncoproteins (Fos/Jun) in the mouse uterus treated with three natural estrogens. Cancer Lett 97: 225–231, 1995

    Article  PubMed  CAS  Google Scholar 

  8. Fujimoto J, Hori M, Ichigo S, et al: Clinical implication of fos and jun expressions and protein kinase activity in endometrial cancers. Eur J Gynaecol Oncol 16: 138–146, 1995

    PubMed  CAS  Google Scholar 

  9. Kumar V, Abbas AK, Fausto N: Robbins and Cotran Pathologic Basis of Disease. Elsevier Saunders, Philadelphia, 2005

    Google Scholar 

  10. Salmi A, Heikkilä P, Lintula S, Rutanen EM: Cellular localization of c-jun messenger ribonucleic acid and protein and their relation to the proliferation marker Ki-67 in the human endometrium. J Clin Endocrinol Metab 83: 1788–1796, 1998

    Article  PubMed  CAS  Google Scholar 

  11. Wisdom R, Johnson RS, Moore C: C-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J 18: 188–197, 1999

    Article  PubMed  CAS  Google Scholar 

  12. Vogt PK, Bos TJ: The oncogene jun and nuclear signaling. TIBS 14: 172–175, 1989

    PubMed  CAS  Google Scholar 

  13. Travers MT, Knowler JT: Oestrogen-induced expression of oncogenes in the immature rat uterus. FEBS Letters 211: 27–30, 1987

    Article  PubMed  CAS  Google Scholar 

  14. Huet-Hudson YM, Andrews GK, Dey SK: Cell type-specific localization of c-myc protein in the mouse uterus: modulation by steroid hormones and analysis of the periimplantation period. Endocrinology 125: 1683–1690, 1989

    PubMed  CAS  Google Scholar 

  15. Cole MD: The myc oncogene: its role in transformation and differentiation. Ann Rev Genet 20:361–384, 1986

    Article  PubMed  CAS  Google Scholar 

  16. Fujimoto J, Hori M, Ichigo S, et al: Tissue differences in the expression of mRNAs of Ha-ras, c-myc, fos and jun in human uterine endometrium, myometrium and leiomyoma under the influence of estrogen/progesterone. Tumor Biol 15: 311–317, 1994

    CAS  Google Scholar 

  17. Salmi A, Carpen O, Rutanen E: The association between c-fos and c-jun expression and estrogen and progesterone receptors is lost in human endometrial cancer. Tumor Biol 20: 202–211, 1999

    Article  CAS  Google Scholar 

  18. Murphy LJ, Murphy LC, Friesen HG: Estrogen induction of Nmyc and c-myc proto-oncogene expression in the rat uterus. Endocrinology 120: 1882–1888, 1987

    PubMed  CAS  Google Scholar 

  19. Silverberg SG: Hyperplasia and carcinoma of the endometrium. Semin Diagn Pathol 5: 135–153, 1988

    PubMed  CAS  Google Scholar 

  20. Silverberg SG, Kurman RJ: Tumors of the uterine corpus and gestational trophoblastic disease. AFIP, Washington DC, 1992

    Google Scholar 

  21. Mikuta JJ: International Federation of Gynecology and Obstetrics Staging of Endometrial Cancer 1988. Cancer 71: 1460–1463, 1993

    PubMed  CAS  Google Scholar 

  22. Salmi A, Rutanen F: C-fos and c-jun expression in human endometrium and myometrium. Mol Cell Endocrinol 117: 233–240, 1996

    Article  PubMed  CAS  Google Scholar 

  23. Thornton JG, Wells M: Oestrogen receptor in glands and stroma of normal and neoplastic human endometrium: a combined biochemical, immunohistochemical, and morphometric study. J Clin Pathol 40: 1437–1442, 1987

    Article  PubMed  CAS  Google Scholar 

  24. Huang SJ, Cheng L, Lewin KJ, Fu YS: Immunohistochemical estrogen receptor assessment in hyperplastic, neoplastic, and physiologic endometria. Pathol Res Pract 187: 487–495, 1991

    PubMed  CAS  Google Scholar 

  25. Papadimitriou CS, Athanasiadou S, Stylianidou A, et al: Immnohistochemical detection of estrogen receptors on paraffin sections of normal, hyperplastic and carcinomatous endometrium. Oncology 49:196–202, 1992

    PubMed  CAS  Google Scholar 

  26. Nunobiki O, Taniguchi E, Ishii A, et al: Significance of hormone receptor status and tumor vessels in normal, hyperplastic and neoplastic endometrium. Pathol Int 53: 846–852, 2003

    Article  PubMed  CAS  Google Scholar 

  27. Neis KJ, Brandner P, Ulrich-Winkelspecht K: The oestrogen receptor (ER) in normal and abnormal uterine tissue. Eur J Cancer 36: S27–36, 2000

    Article  Google Scholar 

  28. Uchikawa J, Shiozawa T, Shih H, et al: Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression. Cancer 98: 2207–2213, 2003

    Article  PubMed  CAS  Google Scholar 

  29. Snijders MP, De Goeij AF, Koudstaal J, et al: Oestrogen and progesterone receptor immunocytochemistry in human hyperplastic and neoplastic endometrium. J Pathol 166: 171–177, 1992

    Article  PubMed  CAS  Google Scholar 

  30. Punnonen R, Mattila J, Kuoppala T, Koivula T: DNA ploidy, cell proliferation and steroid hormone receptors in endometrial hyperplasia and early adenocarcinoma. J Cancer Res Clin Oncol 119:426–429, 1993

    Article  PubMed  CAS  Google Scholar 

  31. Sivridis E, Giatromanolaki A: Prognostic aspects on endometrial hyperplasia and neoplasia. Virchows Arch 439: 118–126, 2001

    Article  PubMed  CAS  Google Scholar 

  32. Carcangiu ML, Chambers JT, Voynick IM, et al: Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part I: Clinical and histologic correlations. Am J Clin Pathol 94: 247–254, 1990.

    PubMed  CAS  Google Scholar 

  33. Chambers JT, Carcangiu ML, Voynick IM, Schwartz PE: Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part II: Correlation between biochemical and immunohistochemical methods and survival. Am J Clin Pathol 94: 255–260, 1990

    PubMed  CAS  Google Scholar 

  34. Bigsby RM, Li A: Differentially regulated immediate early genes in the rat uterus. Endocrinology 134: 1820–1826, 1994

    Article  PubMed  CAS  Google Scholar 

  35. Nephew KP, Tang M, Khan SA: Estrogen differentially affects c-jun expression in uterine tissue compartments. Endocrinology 134: 1827–1834, 1994

    Article  PubMed  CAS  Google Scholar 

  36. Yokoyama Y, Sagara M, Sato S, Saito Y: Value of glutathione Stransferase π and the oncogene products c-jun, c-fos, H-ras, and c-myc as a prognostic indicator in endometrial carcinomas. Gynecol Oncol 68: 280–287, 1998

    Article  PubMed  CAS  Google Scholar 

  37. Odom LD, Barrett JM, Pantazis CG, et al: Immunocytochemical study of ras and myc proto-oncogene polypeptide expression in the human menstrual cycle. Am J Obstet Gynecol 161: 1663–1668, 1989

    PubMed  CAS  Google Scholar 

  38. Jack AS, Kerr IB, Evan G, Lee FD: The distribution of the cmyc oncogene product in malignant lymphomas and various normal tissues as demonstrated by immunocytochemistry. Br J Cancer 53: 713–719, 1986

    PubMed  CAS  Google Scholar 

  39. Schenken RS, Johnson JV, Riehl RM: C-myc protooncogene polypeptide expression in endometriosis. Am J Obstet Gynecol 164: 1031–1037, 1991

    PubMed  CAS  Google Scholar 

  40. Bai MK, Costopoulos JS, Christoforidou BP, Papadimitriou CS: Immunohistochemical detection of the c-myc oncogene product in normal, hyperplastic and carcinomatous endometrium. Oncology 51: 314–319, 1994

    Article  PubMed  CAS  Google Scholar 

  41. Loke SL, Neckers LM, Schwab G, Jaffe ES: C-myc protein in normal tissue: Effects of fixation on its apparent subcellular disribution. Am J Pathol 131: 29–37, 1988

    PubMed  CAS  Google Scholar 

  42. Sato S, Ito K, Ozawa N, Yajima A, Sasano H: Expression of cmyc, epidermal growth factor receptor and c-erbB-2 in human endometrial carcinoma and cervical adenocarcinoma. Tohoku J Exp Med 165: 137–145, 1991

    Article  PubMed  CAS  Google Scholar 

  43. Watson TV, Curling OM, Munn CF, Hudson CN: Oncogene expression in ovarian cancer: A pilot study of c-myc oncoprotein in serous papillary cancer. Gynecol Oncol 28: 137–150, 1987

    Article  PubMed  CAS  Google Scholar 

  44. Monk BJ, Chapman JA, Johnson GA, et al: Correlation of cmyc and HER-2/neu amplification and expression with histopathologic variables in uterine corpus cancer. Am J Obstet Gynecol 171: 1193–1198, 1994

    PubMed  CAS  Google Scholar 

  45. Borst MP, Baker VV, Dixon D, et al: Oncogene alterations in endometrial carcinoma. Gynecol Oncol 38: 364–366, 1990

    Article  PubMed  CAS  Google Scholar 

  46. Ambros RA: C-myc gene expression in stage I endometrioid adenocarcinoma of the uterus. Materia Medica Polona 24: 76–78, 1992

    PubMed  CAS  Google Scholar 

  47. Geisler JP, Geisler HE, Manahan KJ, et al: Nuclear and cytoplasmic c-myc staining in endometrial carcinoma and their relationship to survival. Int J Gynecol Cancer 14: 133–137, 2004

    Article  PubMed  CAS  Google Scholar 

  48. Sasano H, Comerford J, Wilkinson DS, et al: Serous papillary adenocarcinoma of the endometrium. Analysis of proto-oncogene amplification, flow cytometry, estrogen and progesterone receptors, and immunohistochemistry. Cancer 65: 1545–1551, 1990

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, University of Ankara, Ankara, Turkey

    Sema Bircan, Arzu Ensari, Sibel Ozturk & Nural Erdogan

  2. Department of Gynecological Oncology, School of Medicine, University of Ankara, Ankara, Turkey

    Ilkkan Dundar & Firat Ortac

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  1. Sema Bircan
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Correspondence to Sema Bircan.

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Bircan, S., Ensari, A., Ozturk, S. et al. Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium. Pathol. Oncol. Res. 11, 32–39 (2005). https://doi.org/10.1007/BF03032403

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  • DOI: https://doi.org/10.1007/BF03032403

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