Department of Pathology, Acharya Harihar Post-graduate Institute of Cancer, Cuttack, Odisha, India.
Division of Molecular Epidemiology and Public Health, ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, India.
J Gastrointest Cancer. 2024 Sep;55(3):1154-1164. doi: 10.1007/s12029-024-01045-3. Epub 2024 May 18.
Gallbladder cancer (GBC) is a highly aggressive malignant tumor with a poor prognosis. Despite being first described two centuries ago, there are no targeted therapies available beyond conventional cytotoxic therapy. Epidemiological studies have shown that the incidence of gallbladder cancer is higher in females than males. This suggests that the gallbladder may be a female sex hormone-responsive organ, and these hormones might be involved in the pathogenesis of gallbladder cancer. Therefore, we aimed to analyze the expression of ERα and PR in GBC and correlate their expression with clinicopathological variables and overall survival.
A total of 235 histopathologically diagnosed GBC cases were included in this hospital-based cross-sectional study. Clinicopathological data were collected, and the expression of ERα and PR was evaluated by immunohistochemistry.
The mean age of this study population was 55.47 ± 8.45 with range 28-87 years. Females were predominated over male with a male-to-female ratio of 1:3.5. Positive nuclear expression of the ERα and PR was found in 13 (5.5%) and eight (3.4%) cases, respectively. Apart from nuclear staining, cytoplasmic expression of ERα and PR was found in three (1.2%) and 31 (13.2%) cases, respectively. Higher percentage of positive nuclear expression of ER was found in < 50 years age (p value = 0.04), parity > 4 (p value = 0.02), advanced pT stage (T3) (p value = 0.01), lymphovascular invasion (p value = 0.02), and liver invasion (p value = 0.04) which were statistically significant. Higher percentage of PR expression was also observed in < 50 years age (p value = 0.01), and tumor associated with gallstone (p value = 0.04). There was no significant correlation between cytoplasmic expression of ER, PR, and clinicopathological variables. In multivariate analysis, there was no significant correlation between ER or PR positive expression and overall survival.
Although nuclear expression of ERα was significantly associated with progressive disease factors but the positive expression was found in very small percentage of GBC cases. So anti-hormone therapy might be an option in patient with ER α positive gallbladder carcinoma.
胆囊癌(GBC)是一种侵袭性强、预后差的恶性肿瘤。尽管这种肿瘤在两个世纪前就被首次描述,但除了传统细胞毒性治疗外,目前还没有靶向治疗方法。流行病学研究表明,女性胆囊癌的发病率高于男性。这表明胆囊可能是一种女性性激素反应性器官,这些激素可能参与胆囊癌的发病机制。因此,我们旨在分析 ERα 和 PR 在 GBC 中的表达,并将其表达与临床病理变量和总生存期相关联。
本研究为基于医院的病例对照研究,共纳入 235 例经组织病理学诊断的 GBC 病例。收集临床病理资料,采用免疫组织化学法检测 ERα 和 PR 的表达。
该研究人群的平均年龄为 55.47±8.45 岁,范围为 28-87 岁。女性多于男性,男女比例为 1:3.5。分别有 13 例(5.5%)和 8 例(3.4%)患者的 ERα 和 PR 出现核阳性表达。除核染色外,分别有 3 例(1.2%)和 31 例(13.2%)患者的 ERα 和 PR 出现细胞质表达。在年龄<50 岁(p 值=0.04)、产次>4(p 值=0.02)、pT 期较晚(T3)(p 值=0.01)、淋巴管血管侵犯(p 值=0.02)和肝侵犯(p 值=0.04)患者中,ER 核阳性表达的百分比更高,具有统计学意义。在年龄<50 岁(p 值=0.01)和肿瘤与胆石相关的患者中(p 值=0.04),PR 表达也更高。ER 和 PR 的细胞质表达与临床病理变量之间无显著相关性。在多变量分析中,ER 或 PR 阳性表达与总生存期无显著相关性。
尽管 ERα 的核表达与进展性疾病因素显著相关,但在 GBC 病例中阳性表达的比例非常小。因此,对于 ERα 阳性的胆囊癌患者,抗激素治疗可能是一种选择。