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

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.

Keywords

• Endometrial cancer,Adipokines,Apoptosis,Immunohistochemistry

Endometrial kanserde serum adipokinlerin tümör mitotik ve apoptotik aktiviteye etkisi

Öz

Amaç: Endometrial kanser, kadın genital sisteminin en sık görülen malignitesidir. Obezite, endometrial kanserde en önemli risk faktörlerinden biridir. Adipoz doku, birçok biyoaktif madde salgılayarak tıpkı bir endokrin organı gibi işlev görür ve tümör gelişimine katkıda bulunur. Endometrium kanserinde serum adipokin seviyeleri ile tümör mitotik ve apopitotik aktivite düzeyleri arasındaki ilişkinin araştırılması amaçlanmıştır.

Yöntemler: Kesitsel bir çalışma tasarladık. Etik Kurul onayı alındıktan sonra 2014 Temmuz-2014 Aralık tarihleri arasında Ondokuz Mayıs Üniversitesi Tıp Fakültesi Kadın Hastalıkları ve Doğum polikliniğine endometriyal kanserli 38 hasta dahil edildi. Hastalardan preoperatif alınan 5 cc serum örneğinde serum leptin ve adiponektin seviyesi ölçüldü. Hastaların patoloji spesmenleri immünhistokimyasal çalışma ile bcl-2 için boyanma yüzdesi ve şiddeti ve Ki67 için boyanma yüzdesi gözönüne alınarak semikantitatif olarak değerlendirildi. Ayrıca hastaların preoperatif östradiol seviyesi, insülin direnci, vücut yağ oranları ve body mass index (BMI) değerleri belirlendi. İstatistiksel olarak Mann Whitney U Kruskal Wallis ve Spearman’ın Korelasyon testi kullanıldı. P<0,05 için sonuçlar istatistiksel olarak anlamlı kabul edildi.

Bulgular: Çalışmaya alınan hastalar 36-82 yaşlar arasında olup yaş ortalaması 62,5 (10,4) idi. Hastaların ortalama BMI değeri 31,1 (4,8) kg/m2 idi (Aralık: 19-38 kg/m2). FIGO 2010 evreleme sistemine göre 30 hasta (%78) Evre 1, 1 hasta (%2,6) Evre 2,7 hasta (%18,4) Evre 3 olarak dağılım göstermekte idi. Hastaların 6 tanesi (%15,8) grade 1, 20 tanesi (%52,6) grade 2 ve 12 tanesi (%31,6) grade 3 olarak dağılım göstermekte idi. 27 hasta endometrioid tip kalan 11 hasta nonendometrioid tip olarak sınıflandırıldı. Serum leptin ve adiponektin düzeyi ile tümöral dokuda Ki-67 immünhistokimyasal boyanma yüzdesi ve bcl-2 skoru arasında istatistiksel anlamlı korelasyon saptanmadı (P=0,751). Tümöral doku immünhistokimyasal incelemesinde Ki67 için boyanma yüzdesi arttıkça tümörün grade’i de istatistiksel anlamlı olarak arttığı belirlendi (r=0,571 P<0,001). Bcl-2 skoru ile tümör grade veya evresi arasında istatistiksel anlamlı korelasyon saptanmadı (p>0.05). BMI arttıkça serum leptin düzeylerinin istatistiksel anlamlı olarak arttığı saptandı (r=0,341, P=0,036). HOMA-IR arttıkça adiponektin düzeyi istatistiksel anlamlı olarak artmaktaydı (r=0,393, P=0,015). Endometrioid ve non-endometrioid gruplar arasında da; leptin, adiponektin ve leptin/adiponektin düzeyleri yönünden istatistiksel olarak anlamlı farklılık görülmedi (P=0,554, P=0,652). Endometrioid ve non-endometrioid grupları arasında medyan BCL-2 skoru ve Ki-67 yüzdesi yönünden istatistiksel olarak anlamlı farklılık görülmedi (P=0,05).

Sonuç: Serum leptin ve adiponektin düzeyi ile tümöral dokuda Ki-67 immünhistokimyasal boyanma yüzdesi ve bcl-2 skoru arasında istatistiksel anlamlı korelasyon yoktur.

Anahtar Kelimeler

• Endometrium kanseri,Adipokin,Apopitozis,İmmunohistokimya

Kaynakça

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