Uppsala University, Department of Immunology, Genetics and Pathology, Sweden; Science for Life Laboratory, Uppsala, Sweden.
Department of Pathology, University of Turku, Turku, Finland; Department of Gynecology and Obstetrics, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital, Turku, Finland; Department of Gynecology and Obstetrics, Turku University Hospital, Turku, Finland.
Gynecol Oncol. 2015 Jun;137(3):529-37. doi: 10.1016/j.ygyno.2015.03.055. Epub 2015 Apr 7.
For endometrial carcinoma, prognostic stratification methods do not satisfactorily identify patients with adverse outcome. Currently, histology, tumor grade and stage are used to tailoring surgical treatment and to determine the need for adjuvant treatment. Low-risk patients are not considered to require adjuvant therapy or staging lymphadenectomy. For patients with intermediate or high risk, some guidelines recommend tailoring adjuvant treatment according to additional negative prognostic factors. Our objective was to evaluate the biomarker potential of the ASRGL1 protein in endometrial carcinoma.
Using The Human Protein Atlas (www.proteinatlas.org), the l-asparaginase (ASRGL1) protein was identified as an endometrial carcinoma biomarker candidate. ASRGL1 expression was immunohistochemically evaluated with an extensively validated antibody on two independent endometrial carcinoma cohorts (n=229 and n=286) arranged as tissue microarrays. Staining results were correlated with clinical features.
Reduced expression of ASRGL1, defined as <75% positively stained tumor cells, was significantly associated with poor prognosis and reduced disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). In multivariate analysis the hazard ratios for disease-specific survival were 3.55 (95% CI=1.10-11.43; p=0.003) and 3.23 (95% CI=1.53-6.81; p=0.002) in the two cohorts, respectively. Of the 48 cases with Grade 3 Stage I tumor all disease-related deaths were associated with low ASRGL1 expression.
Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended.
对于子宫内膜癌，预后分层方法不能令人满意地识别预后不良的患者。目前，组织学、肿瘤分级和分期用于制定手术治疗方案，并确定是否需要辅助治疗。低危患者不被认为需要辅助治疗或分期淋巴结切除术。对于中高危患者，一些指南建议根据额外的预后不良因素来定制辅助治疗。我们的目的是评估 ASRGL1 蛋白在子宫内膜癌中的生物标志物潜力。
使用人类蛋白质图谱（www.proteinatlas.org），鉴定 l-天冬酰胺酶（ASRGL1）蛋白作为子宫内膜癌的生物标志物候选物。使用经过广泛验证的抗体，对两个独立的子宫内膜癌队列（n=229 和 n=286）进行免疫组织化学评估，这些队列被组织成微阵列。将染色结果与临床特征相关联。
ASRGL1 表达减少，定义为<75%的肿瘤细胞呈阳性染色，与子宫内膜样腺癌（EEA）的不良预后和降低的疾病特异性生存率显著相关。在多变量分析中，两个队列中疾病特异性生存率的危险比分别为 3.55（95%CI=1.10-11.43；p=0.003）和 3.23（95%CI=1.53-6.81；p=0.002）。在 48 例 3 级 1 期肿瘤中，所有与疾病相关的死亡都与 ASRGL1 表达降低有关。
在 EEA 中，ASRGL1 的缺失是预后不良的有力生物标志物，保留 ASRGL1 对生存有积极影响。ASRGL1 免疫组化有可能成为除分级和分期外，根据其他预后因素定制辅助治疗的额外预后工具。
