Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Uppsala, Sweden.
Gynecol Oncol. 2018 Jan;148(1):197-203. doi: 10.1016/j.ygyno.2017.10.025. Epub 2017 Oct 31.
Loss of Asparaginase-like protein 1 (ASRGL1) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGL1 expression in endometrial carcinoma precursor lesion and metastases.
782 primary endometrial carcinomas, 90 precursor lesions (complex atypical hyperplasia), and 179 metastases (from 87 patients) were evaluated for ASRGL1 expression by immunohistochemistry in relation to clinical and histopathological data. ASRGL1 mRNA level was investigated in 237 primary tumors and related to survival and ASRGL1 protein expression.
Low expression of ASRGL1 protein and ASRGL1 mRNA predicted poor disease specific survival (P<0.001). In multivariate survival analyses ASRGL1 had independent prognostic value both in the whole patient cohort (Hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.04-2.26, P=0.031) and within the endometrioid subgroup (HR: 2.64, CI: 1.47-4.74, P=0.001). Low ASRGL1 expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGL1 was lost in the majority of metastatic lesions.
In a prospective setting ASRGL1 validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival, and is demonstrated for the first time to have independent prognostic value in the entire endometrial carcinoma patient population.
天冬酰胺酶样蛋白 1（ASRGL1）的缺失被认为是子宫内膜癌的一种预后生物标志物。我们的目的是在一个前瞻性收集的独立患者队列中验证这一点，并评估 ASRGL1 在子宫内膜癌前病变和转移中的表达。
通过免疫组织化学方法，评估了 782 例原发性子宫内膜癌、90 例前病变（复杂不典型增生）和 179 例转移（来自 87 例患者）的 ASRGL1 表达情况，并与临床和组织病理学数据相关联。在 237 例原发性肿瘤中检测了 ASRGL1mRNA 水平，并与生存和 ASRGL1 蛋白表达相关联。
ASRGL1 蛋白和 ASRGL1mRNA 的低表达预测疾病特异性生存不良（P<0.001）。在多变量生存分析中，ASRGL1 在整个患者队列（风险比（HR）：1.53，95%置信区间（CI）：1.04-2.26，P=0.031）和子宫内膜样亚组（HR：2.64，CI：1.47-4.74，P=0.001）中均具有独立的预后价值。与高级别子宫内膜样和非子宫内膜样原发性肿瘤相比，低级别子宫内膜样原发性肿瘤患者中 ASRGL1 低表达的频率较低，并且大多数转移性病变中丢失了 ASRGL1。
在前瞻性研究中，ASRGL1 验证为子宫内膜癌的一种强有力的预后生物标志物。ASRGL1 的缺失与侵袭性疾病和不良生存相关，并且首次在整个子宫内膜癌患者人群中显示出独立的预后价值。
