Role of nesfatin in endometrial cancers

Aims: Endometrial cancers (ECs) represent a heterogeneous group of cancers with different types of histology, etiology, and prognosis. The largest risk factors for EC are obesity and diabetes. Nesfatin regulates food intake and glucose homeostasis. The aim of this multicentre study was closer recognition of nesfatin and other molecular factors in ECs. Materials and Methods: Using sections of paraffinembedded preparations and immunohistochemistry, the expression of nesfatin (NESF 1), estrogen receptors (ER α and β1), and progesterone receptor (PR) was examined in 146 cancer patients (115 EC type I and 33 type II). Results: In EC type I, a higher expression of PR, but lower ER β1 was found. No significant difference was detected in NESF 1 and ER α expression between the two types of ECs. ER α expression was higher in early stages of EC, and in more advanced cases ER β1 staining was weaker. In EC types I and II, a high expression of NESF 1 correlated with a high expression of ER α. Lower nesfatin expression correlated with low cells differentiation (grading) in EC type I. A tendency towards high expression of nesfatin was noted in patients with a lack of ER β1 expression. No correlation was found between the expression of NESF 1 and PR in any of the groups. Conclusions: The role of nesfatin in EC is still poorly understood. In EC type I, a high expression of NESF 1 seems to represent a favourable prognostic factor, while in type II its role is still unknown.

Enodmetrial cancer; Nesfatin; Molecular factors

[1] Colombo N., Creutzberg C., Amant F., Bosse T., González-Martín A., Ledermann J., et al.: “ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up”. Int. J. Gynecol. Cancer, 2016, 25, 1.

[2] Murali R., Soslow RA., Weigelt B: “Classification of endometrial carcinoma: more than two types”. Lancet Oncol., 2014, 15, e268.

[3] Globocan 2012: “Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012”. Available at: http://globocan.iarc.fr

[4] Bokhman J.V.: ‘Two pathogenetic types of endometrial carcinoma”. Gynecol. Oncol., 1983, 15, 10.

[5] Tangjitgamol S., Khunnarong J., Srijaipracharoen S.: “Medical morbidities in endometrial cancer patients”. Int. J. Gynecol. Cancer, 2014, 24, 1623.

[6] Huang M., Djordjevic B., Yates MS., Urbauer D., Sun C., Burzawa J., et al.: “Molecular pathogenesis of endometrial cancers in patients with Lynch syndrome”. Cancer, 2013, 119, 3027.

[7] Hapangama D.K., Kamal A.M., Bulmer J.N.: “Estrogen receptor β: the guardian of the endometrium”. Hum. Reprod. Update, 2015, 21, 174.

[8] 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.

[9] Hampel H., Frankel W., Panescu J., Lockman J., Sotamaa K., Fix D., et al.: “Screening for Lynch syndrome (hereditary nonpolyposis Colorectal cancer) among endometrial cancer patients”. Cancer Res., 2006, 66, 7810.

[10] Sho T., Hachisuga T., Nguyen TT., Urabe R., Kurita T., Kagami S., et al.: “Expression of estrogen receptors-α as a prognostic factor in patients with uterine serous carcinoma”. Int. J. Gynecol. Cancer, 2014, 24, 102.

[11] Attias-Geva Z., Bentov I., Kidron D., Amichay K., Sarfstein R., Fishman A., 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, 1570.

[12] Togami S., Sasajima Y., Oi T., Ishikawa M., Onda T., Ikeda S., 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, 926.

[13] Rafii S., Dawson P., Williams S., Pascoe J.S., Nevin J.N., Sundar S., et al.: “Is uterine serous carcinoma a part of hereditary breast cancer syndrome?” J. Clin. Oncol., 31, 2013; abstr 5587.

[14] Bruchim I., Amichay K., Kidron D., Attias Z., Biron-Shental T., Drucker L., et al.: “BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma”. Int. J. Gynecol. Cancer, 2010, 20, 1148.

[15] Setiawan V.W., Yang H.P., Pike M.C., McCann S.E., Yu H., Xiang Y.B., et al.: “Type I and II endometrial cancers: have they different risk factors?” J. Clin. Oncol., 2013, 31, 2607.

[16] ParK J.Y., Nam J.H., Kim Y.T., Kim Y.M, Kim J.H., Kim D.Y., et al.: “Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients”. Virchows Arch., 2013, 462, 289.

[17] The Cancer Genome Atlas Research Network: “Integrated genomic characterization of endometrial carcinoma”. Nature, 2013, 497, 67.

[18] Takagi K., Miki Y., Tanaka S., Hashimoto CH., Watanabe M., Sasano H., et al.: “Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration”. Endocrin. J., 2016, 63, 297.

[19] Zhang Z., Li L., Yang M., Liu H., Boden G., Yang G., et al.: “Increased plasma levels of nesfatin-1 in patients with newly diagnosed type 2 diabetes mellitus”. Exp. Clin. Endocrinol. Diabetes, 2012, 120, 91.

[20] Ademoglu E.N., Gorar S., Carlıoglu A.,Yazıcı H., Dellal F.D., Berberoglu Z., et al.: “Plasma nesfatin-1 levels are increased in patients with polycystic ovary syndrome”. J. Endocrinol. Invest., 2014, 37, 715.

[21] Häring J., Schüler S., Lattrich C., Ortmann O., Treeck O.: “Role of estrogen receptor β in gynecological cancer”. Gynecol. Oncol., 2012, 127, 673.

[22] Chakravarty D., Srinivasan R., Ghosh S., Gopalan S., Rajwanshi A., Majumdar S.: “Estrogen receptor beta1 and the beta2/betacx isoforms in nonneoplastic endometrium and in endometrioid carcinoma”. Int. J. Gynecol. Cancer, 2007, 17, 905.