Impact of serum adipokines on tumor mitotic and apoptotic activity in endometrial cancer

Authors

Keywords:

Endometrial cancer, Adipokines, Apoptosis, Immunohistochemistry

Abstract

Aim: Endometrial cancer is the most common malignancy of female genital system. Obesity is one of the most important risk factors in endometrial cancer. Adipose tissue functions just like an endocrine organ by secreting many bioactive substances and contributes to tumor development. The aim of this study was to investigate the correlation between serum adipokine levels and tumor mitotic and apoptotic activity levels in endometrial cancer. 

Methods: We designed a cross-sectional study. After obtaining the approval of Ethics Committee, 38 patients with endometrial cancer admitted between 2014 July-2014 December to Obstetrics and Gynecology outpatient clinic of Ondokuz Mayıs University, Faculty of Medicine were included in the study. Serum leptin and adiponectin levels were measured in 5 cc serum samples taken from the patients preoperatively. The pathology specimens of the patients were semiquantitatively evaluated with immunohistochemical study considering the percentage and intensity of staining for bcl-2 and the percentage of staining for Ki67. Moreover, preoperative estradiol levels, insulin resistance, body fat percentages and body mass index (BMI) values were determined. The Mann Whitney U test, Kruskal Wallis and Spearman's Correlation test were used statistically. The results were considered statistically significant for P<0.05. 

Results: The patients included in the study were between 36-82 years of age and the mean age was 62.5 (10.4) years. The mean BMI value of the patients was 31.1 (4.8) kg/m2 (range: 19-38 kg/m2). According to the FIGO 2010 staging system, the distribution of the patients were as follows: 30 patients (78%) Stage 1, 1 patient (2.6%) Stage 2 and 7 patients (18.4%) Stage 3. Of the patients, 6 (15.8%) had grade 1, 20 (52.6%) had grade 2 and 12 (31.6%) had grade 3. Twenty-seven patients were classified as endometrioid type and 11 patients were classified as nonendometrioid type. There was no statistically significant correlation between serum leptin and adiponectin levels and percentage of Ki-67 immunohistochemical staining in tumoral tissue and bcl-2 score (P=0.05). In the immunohistochemical examination of tumoral tissue, it was found that tumor grade statistically significantly increased as the staining percentage for Ki67 increased (r=0.571, P<0.001). There was no statistically significant correlation between Bcl-2 score and tumor grade or stage (P=0.751). It was found that serum leptin levels significantly increased as BMI increased (r=0.341, P=0.036). As HOMA-IR increased, adiponectin level statistically significantly increased (r=0.393, P=0.015). There was also no statistically significant difference between the endometrioid and non-endometrioid groups in terms of leptin, adiponectin and leptin/adiponectin levels (P=0.554, P=0.652). There was no statistically significant difference between the endometrioid and non-endometrioid groups in terms of median BCL-2 score and Ki-67 percentage (P=0.05). 

Conclusion: There was no correlation between serum leptin and adiponectin levels and Ki-67 immunohistochemical staining percentage and bcl-2 score.

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References

Boden G. Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes. 2011 Apr;18(2):139-43.

Stephenson GD, Rose DP. Breast cancer and obesity: an update. Nutr Cancer. 2003;45(1):1-16.

Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2004 Sep;92(3):347-55.

Huang L, Li C. Leptin: a multifunctional hormone. Cell Res. 2000 Jun;10(2):81-92.

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 May;85(5):1946-50.

Hanley AJ, Bowden D, Wagenknecht LE, Balasubramanyam A, Langfeld C, Saad MF, et al. Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans. J Clin Endocrinol Metab. 2007 Jul;92(7):2665-71.

Finucane FM, Luan J, Wareham NJ, Sharp SJ, O'Rahilly S, Balkau B, et al. Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals. Diabetologia. 2009 Nov;52(11):2345-9.

Oda N, Imamura S, Fujita T, Uchida Y, Inagaki K, Kakizawa H, Hayakawa N, Suzuki A, Takeda J, Horikawa Y, Itoh M. The ratio of leptin to adiponectin can be used as an index of insulin resistance. Metabolism. 2008 Feb;57(2):268-73.

Guadagni F, Roselli M, Martini F, Spila A, Riondino S, D'Alessandro R, et al. Prognostic significance of serum adipokine levels in colorectal cancer patients. Anticancer Res. 2009 Aug;29(8):3321-7.

Chen DC, Chung YF, Yeh YT, Chaung HC, Kuo FC, Fu OY, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006 Jun 8;237(1):109-14.

Xu GF, Zhu F, Liu CX, Li H, Shi M. [Study on serum leptin level of urban resident and the relationship between body mass index, blood lipid, insulin and leptin level]. Wei Sheng Yan Jiu. 2005 Mar;34(2):205-7.

Sierra-Honigmann MR, Nath AK, Murakami C, García-Cardeña G, Papapetropoulos A, Sessa WC, et al. Biological action of leptin as an angiogenic factor. Science. 1998 Sep 11;281(5383):1683-6.

Ashizawa N, Yahata T, Quan J, Adachi S, Yoshihara K, Tanaka K. Serum leptin-adiponectin ratio and endometrial cancer risk in postmenopausal female subjects. Gynecol Oncol. 2010 Oct;119(1):65-9.

Gao J, Tian J, Lv Y, Shi F, Kong F, Shi H, Zhao L. Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer Sci. 2009 Mar;100(3):389-95.

Cong L, Gasser J, Zhao J, Yang B, Li F, Zhao AZ. Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. Endocr Relat Cancer. 2007 Sep;14(3):713-20.

Yu Ma, Zhiwei Liu, Yan Zhang, et al. Serum leptin, adiponectin and endometrial cancer risk in Chinese women. J Gynecol Oncol. 2013 Oct; 24(4):336–41.

Friedenreich CM, Langley AR, Speidel TP, et al. Case-control study of markers of insulin resistance and endometrial cancer risk. Endocr Relat Cancer. 2012 Nov 9;19(6):785-92.

Cymbaluk A, Chudecka-Głaz A, Rzepka-Górska I, et al. Leptin levels in serum depending on Body Mass Index in patients with endometrial hyperplasia and cancer. Eur J Obstet Gynecol Reprod Biol. 2008 Jan;136(1):74-7.

Mihu D, Ciortea R, Mihu CM, et al. Abdominal adiposity through adipocyte secretion products, a risk factor for endometrial cancer. Gynecol Endocrinol. 2013 May;29(5):448-51.

Sharma D, Saxena NK, Vertino PM. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr Relat Cancer. 2006 Jun;13(2):629-40.

Henderson GS, Brown KA, Perkins SL, et al. bcl-2 is down-regulated in atypical endometrial hyperplasia and adenocarcinoma. Mod Pathol. 1996 Apr;9(4):430-8.

Vaskivuo TE , Stenbäck F, Tapanainen JS. Apoptosis and apoptosis-related factors Bcl-2, Bax, tumor necrosis factor-alpha, and NF-kappaB in human endometrial hyperplasia and carcinoma. Cancer. 2002 Oct 1;95(7):1463-71.

Zheng Y, Peng Z, Wang H. A study of Bcl-2 expression in normal endometrium and endometrial carcinoma. Hua Xi Yi Ke Da Xue Xue Bao. 1999 Mar;30(1):92-5.

Canlorbe G, Laas E, Bendifallah S, et al. Contribution of immunohistochemical profile in assessing histological grade of endometrial cancer. Anticancer Res. 2013 May;33(5):2191-8.

Pinheiro A, Antunes A Jr, Andrade L, et al. Expression of hormone receptors, Bcl 2, Cox 2 and Ki67 in benign endometrial polyps and their association with obesity. Mol Med Rep. 2014 Jun;9(6):2335-41.

Villavicencio A, Aguilar G, Argüello G, et al. The effect of overweight and obesity on proliferation and activation of AKT and ERK in human endometria. Gynecol Oncol. 2010 Apr;117(1):96-102.

Yuan Y, Zhang J, Cai L, et al. Leptin induces cell proliferation and reduces cell apoptosis by activating c-myc in cervical cancer. Oncol Rep. 2013 Jun;29(6):2291-6.

Jeong YJ, Bong JG, Park SH, et al. Expression of leptin, leptin receptor, adiponectin, and adiponectin receptor in ductal carcinoma in situ and invasive breast cancer. J Breast Cancer. 2011 Jun;14(2):96-103.

Vona-Davis L, Rose DP, Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer. 2007 Jun;14(2):189-206.

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Published

2019-07-29

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Research Article

How to Cite

1.
Özdemir A, Karlı P, Kökçü A, Kefeli M. Impact of serum adipokines on tumor mitotic and apoptotic activity in endometrial cancer. J Surg Med [Internet]. 2019 Jul. 29 [cited 2023 Feb. 6];3(7):469-75. Available from: https://jsurgmed.com/article/view/581498