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ISSN: 1734-1922
Archives of Medical Science
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1/2017
vol. 13
 
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abstract:
Basic research

Leptin receptor expression during the progression of endometrial carcinoma is correlated with estrogen and progesterone receptors

Luis Fernando Méndez-López, Angel Zavala-Pompa, Elva I. Cortés-Gutiérrez, Ricardo M. Cerda-Flores, Martha I. Davila-Rodriguez

Arch Med Sci 2017; 13, 1: 228–235
Online publish date: 2016/12/19
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Introduction: The hormone leptin, which is produced in the adipose tissue, may influence tumorigenesis directly via its receptor (Ob-R). Thus, a role for Ob-R in endometrial carcinogenesis has been proposed. However, most studies neither included samples of the entire histological progression of endometrial carcinoma nor examined Ob-R jointly with the estrogen and progesterone receptors (ER and PR, respectively).

Material and methods: To determine the fluctuations of Ob-R, ER, and PR during the histological progression of endometrial carcinoma, we assessed their expression via immunohistochemistry (IHC) in six histological types of endometrium (proliferative, secretory, nonatypical and atypical hyperplasia, and endometrioid and nonendometrioid endometrial carcinoma), in which we performed histopathological and digital scoring for the quantification of receptors.

Results: We found that Ob-R expression was positively correlated with that of ER and PR (r = 1, p < 0.001; r = 0.943, p < 0.005, respectively), and there was a significant difference in Ob-R expression among proliferative normal endometrium, hyperplasias, and carcinomas, according to their relative digitally scored Ob-R expression (p < 0.001). In addition, we observed that Ob-R expression in the secretory endometrium was more similar to that of carcinomas than to its proliferative counterpart.

Conclusions: These results indicate that Ob-R expression fluctuates during endometrial carcinogenesis in correlation with ER and PR, suggesting that Ob-R expression in vivo is highly dependent on estrogen and progesterone activities in the endometrium and on its ER and PR status, as suggested previously by in vitro studies.
keywords:

Ob-R, endometrial carcinoma, immunohistochemistry

references:
Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004; 4: 579-91.
Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, Escudero-De los Rios P, Salmeron-Castro J, Hernandez-Avila M. Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Res 1999; 59: 3658-62.
Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev 2002; 11: 1531-43.
Gottwald L, Dukowicz A, Piekarski J, et al. Isolated metastasis to the foot as an extremely rare presenting feature of primary endometrial cancer. Arch Med Sci 2012; 8: 172-4.
Lessey BA, Killam AP, Metzger DA, Haney AF, Greene GL, McCarty KS Jr. Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle. J Clin Endocrinol Metab 1988; 67: 334-40.
Stępień M, Stępień A, Banach M, et al. New obesity indices and adipokines in normotensive patients and patients with hypertension comparative pilot analysis. Angiology 2014; 65: 333-42.
Huang L, Li C. Leptin: a multifunctional hormone. Cell Res 2000; 10: 81-92.
Stępień M, Wlazeł RN, Paradowski M, et al. Serum concentrations of adiponectin, leptin, resistin, ghrelin and insulin and their association with obesity indices in obese normo-and hypertensive patients – pilot study. Arch Med Sci 2012; 8: 431-6.
Gao J, Tian J, Lv Y, et al. Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer Sci 2009; 100: 389-95.
Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol 2000; 199: 15-24.
Petridou E, Belechri M, Dessypris N, et al. Leptin and body mass index in relation to endometrial cancer risk. Ann Nutr Metab 2002; 46: 147-51.
Carino C, Olawaiye AB, Cherfils S, et al. Leptin regulation of proangiogenic molecules in benign and cancerous endometrial cells. Int J Cancer 2008; 123: 2782-90.
Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83: 1263-71.
Yuan SS, Tsai KB, Chung YF, et al. Aberrant expression and possible involvement of the leptin receptor in endometrial cancer. Gynecol Oncol 2004; 92: 769-75.
Bogusiewicz M, Semczuk A, Gogacz M, Skomra D, Jakowicki JA, Rechberger T. Lack of correlation between leptin receptor expression and PI3-K/Akt signaling pathway proteins immunostaining in endometrioid-type endometrial carcinomas. Cancer Lett 2006; 238: 61-8.
Jongen V, Briet J, de Jong R, et al. Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol 2009; 112: 537-42.
Kitawaki J, Koshiba H, Ishihara H, Kusuki I, Tsukamoto K, Honjo H. Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle. J Clin Endocrinol Metab 2000; 85: 1946-50.
Koda M, Sulkowska M, Wincewicz A, et al. Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer. Ann N Y Acad Sci 2007; 1095: 90-8.
Méndez-López LF, Dávila-Rodríguez MI, Zavala-Pompa A, Torres-López E, González-Martínez BE, López-Cabanillas-Lomelí M. Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients. Biomed Rep 2013; 1: 659-63.
Gates EJ, Hirschfield L, Matthews RP, Yap OW. Body mass index as a prognostic factor in endometrioid adenocarcinoma of the endometrium. J Natl Med Assoc 2006; 98: 1814-22.
Silverberg SG. Problems in the differential diagnosis of endometrial hyperplasia and carcinoma. Mod Pathol 2000; 13: 309-27.
Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol 1975; 122: 262-3.
Lacey JV, Jr Mutter GL, Nucci MR, et al. Risk of subsequent endometrial carcinoma associated with endometrial intraepithelial neoplasia classification of endometrial biopsies. Cancer 2008; 113: 2073-81.
Mazur MT, Kurman R. Diagnosis of endometrial biopsies and curettings: a practical approach (Second ed.). Springer Science and Business Media, New York 2005.
van Diest PJ, van Dam P, Henzen-Logmans SC, et al. A scoring system for immunohistochemical staining: consensus report of the task force for basic research of the EORTC-GCCG. European Organization for Research and Treatment of Cancer-Gynaecological Cancer Cooperative Group. J Clin Pathol 1997; 50: 801-4.
Pedrycz A, Siermontowski P. Influence of L-arginine on expression of HSP70 and p-53 proteins – early biomarkers of cellular danger in renal tubular cells. Immunohistochemical assessment. Arch Med Sci 2013; 9: 719-23.
Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol 2001; 23: 291-9.
Cornish TC, Haluska MK. Color deconvolution for the analysis of tissue microarrays. Anal Quant Cytol Histol 2009; 31: 304-12.
Wells M. Hyperplasias of the endometrium. Elsevier Churchill Livingstone, Philadelphia 2004.
Gry M, Rimini R, Strömberg S, et al. Correlations between RNA and protein expression profiles in 23 human cell lines. BMC Genomics 2009; 10: 365.
Koshiba H, Kitawaki J, Ishihara H, et al. Progesterone inhibition of functional leptin receptor mRNA expression in human endometrium. Mol Hum Reprod 2001; 7: 567-72.
Henderson BE, Feigelson HS. Hormonal carcinogenesis. Carcinogenesis 2000; 21: 427-33.
Shimizu H, Shimomura Y, Nakanishi Y, et al. Estrogen increases in vivo leptin production in rats and human subjects. J Endocrinol 1997; 154: 285-92.
Duggal PS, Van Der Hoek KH, Milner CR, et al. The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology 2000; 141: 1971-6.
Lacey JV Jr, Ioffe OB, Ronnett BM, et al. Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan. Br J Cancer 2008; 98: 45-53.
Balmer NN, Richer JK, Spoelstra NS, Torkko KC, Lyle PL, Singh M. Steroid receptor coactivator AIB1 in endometrial carcinoma, hyperplasia and normal endometrium: correlation with clinicopathologic parameters and biomarkers. Mod Pathol 2006; 19: 1593-605.
Auwerx J, Staels B. Leptin. Lancet 1988; 351: 737-42.
Li M, Zhao L, Qi W, et al. Clinical implications and prognostic value of five biomarkers in endometrial carcinoma. Chin German J Clin Oncol 2013; 12: 586-91.
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