Gupta Amit, Gupta Sweety, Mani Rishit, Durgapal Prashant, Goyal Bela, Rajput Deepak, Rao Shalinee, Dhar Puneet, Gupta Manoj, Kishore Sanjeev, Kant Ravi
Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.
Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.
J Carcinog. 2021 Jun 9;20:7. doi: 10.4103/jcar.JCar_4_21. eCollection 2021.
Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging.
This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry.
Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 - 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ = 9.886, = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ = 7.017, = 0.037 and χ = 5.861, = 0.033) respectively.
The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.
胆囊癌在全球发病率呈现出显著差异,在某些地区和种族中达到了流行水平。其差异的基础在于环境暴露和致癌的内在遗传易感性的不同。关于胆囊癌(GBC)的基因和分子改变的信息很少。因此,我们评估了GBC中分子标志物的表达,并研究了它们与临床病理分期的相关性。
这项前瞻性观察研究于2017年7月至2020年7月对新诊断的GBC患者进行。在完成全面分期检查后,通过免疫组织化学检测GBC活检样本石蜡块中分子标志物雌激素受体(ER)、孕激素受体(PR)、p53、p16、人表皮生长因子受体2(HER 2-neu)、生存素、zeste同源物2增强子(EZH2)和环氧化酶-2(COX-2)的表达。
本研究纳入了50例新诊断的胆囊癌患者。年龄范围为29 - 69岁(平均53.42岁)。p53是最常见的阳性标志物,74%的患者呈阳性,生存素为58%,COX-2为44%,p16为42%,而Her 2 neu和EZH-2各有16%的患者呈阳性。GBC患者中无一例ER或PR呈阳性。在组织学分级和Her 2 neu的分布方面,各亚组之间存在显著差异(χ = 9.886,P = 0.014),但与其他标志物无关。此外,p16和p53的分布与分期分别存在显著差异(χ = 7.017,P = 0.037和χ = 5.86I,P = 0.033)。
本研究显示了分子标志物Her2 neu、p53、p16、生存素、COX-2和EZH-2在GBC中的表达。现在时机已到,建立这种高致死性恶性肿瘤的早期生物标志物也是当务之急。它未来可用于疾病的早期检测和靶向治疗。