Anggorowati Nungki, Ghozali Ahmad, Widodo Irianiwati, Sari Dwi Cahyani Ratna, Mansyur Romi Muhammad, Arfian Nur
Department of Anatomical Pathology, Universitas Gadjah Mada/Sardjito Hospital, Yogyakarta, Indonesia.
Department of Anatomy, Universitas Gadjah Mada/Sardjito Hospital, Yoyakarta, Indonesia.
Iran J Med Sci. 2018 May;43(3):286-295.
Heparanase and endothelin-1/endothelin A receptor (ET-1/ETR) expressions increase in cancer. This condition enhances tumor progression and correlates with poor survival. Limited data are documented regarding the role of heparanase and ET-1/ETR in epithelial ovarian cancer (EOC). We sought to characterize the correlation between heparanase and ET-1/ETR in EOC.
Thirty patients with benign and malignant ovarian neoplasms were recruited in this study. Neoplasm subtypes were diagnosed by pathologists. RNA extraction was done in fresh frozen neoplasms while immunohistochemical (IHC) staining was done on ETAR, heparanase, and proliferation (Ki-67 antigen) in paraffin sections. Reverse transcriptase PCR was done to quantify the expression of preproET-1 (ppET-1), ETAR, and heparanase. ETAR and heparanase histoscores were done based on IHC staining. The Independent Samples Test, ANOVA, and correlations were used for statistical analysis.
Heparanase and ETAR histoscores, ppET-1 and ETAR mRNA levels, and Ki-67 were significantly higher in the group with EOC than in the benign or borderline group, regardless of the histopathological types. The heparanase histoscore correlated with the ETAR histoscore (r=0.484, P=0.007) and the ETAR mRNA level (r=0.551, P=0.003). The level of ppET-1 mRNA correlated with both ETAR mRNA level and ETAR histoscore (r=0.603, P=0.001 and r=0.455, P=028, respectively). The ovarian neoplasms with high ppET-1 mRNA levels also tended to have high heparanase mRNA levels; however, the correlation was weak (r=0.354, P=0.07). Ki-67 correlated with the heparanase and ETAR histoscores (r=0.381, P=0.038 and r=0.477, P=0.008, respectively).
Heparanase and ETAR were upregulated in EOC, and the correlation between heparanase and ETAR expressions was also elucidated in the current study.
硫酸乙酰肝素酶和内皮素-1/内皮素A受体（ET-1/ETR）的表达在癌症中增加。这种情况会促进肿瘤进展，并与不良预后相关。关于硫酸乙酰肝素酶和ET-1/ETR在上皮性卵巢癌（EOC）中的作用，相关数据有限。我们试图明确EOC中硫酸乙酰肝素酶与ET-1/ETR之间的相关性。
本研究招募了30例患有良性和恶性卵巢肿瘤的患者。肿瘤亚型由病理学家诊断。在新鲜冷冻肿瘤中进行RNA提取，同时在石蜡切片上对ETAR、硫酸乙酰肝素酶和增殖标志物（Ki-67抗原）进行免疫组织化学（IHC）染色。进行逆转录聚合酶链反应以定量前内皮素原-1（ppET-1）、ETAR和硫酸乙酰肝素酶的表达。基于IHC染色计算ETAR和硫酸乙酰肝素酶的组织学评分。采用独立样本检验、方差分析和相关性分析进行统计学分析。
无论组织病理学类型如何，EOC组的硫酸乙酰肝素酶和ETAR组织学评分、ppET-1和ETAR mRNA水平以及Ki-67均显著高于良性或交界性组。硫酸乙酰肝素酶组织学评分与ETAR组织学评分（r=0.484，P=0.007）以及ETAR mRNA水平（r=0.551，P=0.003）相关。ppET-1 mRNA水平与ETAR mRNA水平和ETAR组织学评分均相关（分别为r=0.603，P=0.001和r=0.455，P=0.028）。ppET-1 mRNA水平高的卵巢肿瘤往往硫酸乙酰肝素酶mRNA水平也高；然而，相关性较弱（r=0.354，P=0.07）。Ki-67与硫酸乙酰肝素酶和ETAR组织学评分相关（分别为r=0.381，P=0.038和r=0.477，P=0.008）。
EOC中硫酸乙酰肝素酶和ETAR上调，本研究还阐明了硫酸乙酰肝素酶与ETAR表达之间的相关性。
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