Asparaginase-like protein 1 as a prognostic tissue biomarker in clinicopathologically and molecularly characterized endometrial cancer.

OBJECTIVE: Prognostic stratification of endometrial cancer involves the assessment of stage, uterine risk factors, and molecular classification. This process can be further refined through annotation of prognostic biomarkers, notably L1 cell adhesion molecule (L1CAM) and hormonal receptors. Loss of asparaginase-like protein 1 (ASRGL1) has been shown to correlate with poor outcome in endometrial cancer. Our objective was to assess prognostication of endometrial cancer by ASRGL1 in conjunction with other available methodologies. STUDY DESIGN: This was a retrospective study of patients who underwent primary treatment at a single tertiary center. Tumors were molecularly classified by the Proactive Molecular Risk Classifier for Endometrial Cancer. Expression of ASRGL1, L1CAM, estrogen receptor, and progesterone receptor was determined by immunohistochemistry. ASRGL1 expression intensity was scored into four classes. RESULTS: In a cohort of 775 patients, monitored for a median time of 81 months, ASRGL1 expression intensity was related to improved disease-specific survival in a dose-dependent manner (P < 0.001). Low expression levels were associated with stage II-IV disease and presence of uterine factors, i.e. high grade, lymphovascular space invasion, and deep myometrial invasion (P < 0.001 for all). Among the molecular subgroups, low expression was most prevalent in p53 abnormal carcinomas (P < 0.001). Low ASRGL1 was associated with positive L1CAM expression and negative estrogen and progesterone receptor expression (P < 0.001 for all). After adjustment for stage and uterine factors, strong ASRGL1 staining intensity was associated with a lower risk for cancer-related deaths (hazard ratio 0.56, 95 % confidence interval 0.32-0.97; P = 0.038). ASRGL1 was not associated with the outcome when adjusted for stage, molecular subgroups, L1CAM, and hormonal receptors. When analyzed separately within the different molecular subgroups, ASRGL1 showed an association with disease-specific survival specifically in "no specific molecular profile" subtype carcinomas (P < 0.001). However, this association became nonsignificant upon controlling for confounders. CONCLUSIONS: Low ASRGL1 expression intensity correlates with poor survival in endometrial cancer. ASRGL1 contributes to more accurate prognostication when controlled for stage and uterine factors. However, when adjusted for stage and other biomarkers, including molecular subgroups, ASRGL1 does not improve prognostic stratification.

Increased expression of ASRGL1 in invasive ductal carcinoma and its association with estrogen-progesterone receptor status of tumors.

AIMS: Human asparaginase-like protein 1 (ASRGL1) is closely related to tumor growth. ASRGL1 can significantly promote cell proliferation and suppress apoptosis. To date, high levels of expression of ASRGL1 have been reported in various tumors, but the function of ASRGL1 in carcinogenesis is still not well understood. In this study, we aimed to immunohistochemically investigate the expression of ASRGL1 in non-neoplastic breast tissue and invasive ductal carcinoma. METHODS AND RESULTS: ASRGL1 was evaluated immunohistochemically in 148 invasive ductal carcinomas and 105 nonneoplastic breast tissue samples to assess the impact on breast cancer development and its association with clinicopathologic features. ASRGL1 was observed positive in 63 (42.6%) and negative in 85 (57.4%) invasive ductal carcinoma. In nonneoplastic breast tissue, 24 (22.9%) cases were ASRGL1 positive and 81 (77.1%) were negative. A significant difference was observed between invasive ductal carcinoma and nonneoplastic breast tissue in terms of ASRGL1 expression, and ASRGL1 expression was increased in invasive ductal carcinoma (P = .001). Most estrogen receptor-negative tumors and progesterone receptor-negative tumors were also negative with ASRGL1 and the difference was significant (P = .006 and P = .001, respectively). The correlation between the ASRGL1 expression of the tumors and event-free survival or overall survival was not significant (P>.05). CONCLUSIONS: ASRGL1 may play a role in increasing cell proliferation and breast cancer development. ASRGL-1 expression in breast cancer closely correlates with the hormone receptor status of the tumor. In breast cancer, ASRGL-1 expression does not contribute to predicting tumor behavior.

Asparaginase-like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study.

OBJECTIVE: Correct preoperative identification of high-risk patients is important to optimise surgical treatment and improve survival. We wanted to explore if asparaginase-like protein 1 (ASRGL1) expression in curettage could predict lymph node metastases and poor outcome, potentially improving preoperative risk stratification. DESIGN: Multicentre study. SETTING: Ten hospitals in Norway, Sweden and Belgium. POPULATION: Women diagnosed with endometrial carcinoma. METHODS: ASRGL1 expression in curettage specimens from 1144 women was determined by immunohistochemistry. MAIN OUTCOME MEASURES: ASRGL1 status related to disease-specific survival, lymph node status, preoperative imaging parameters and clinicopathological data. RESULTS: ASRGL1 expression had independent prognostic value in multivariate survival analyses, both in the whole patient population (hazard ratio (HR) 1.63, 95% CI 1.11-2.37, P = 0.012) and in the low-risk curettage histology subgroup (HR 2.54, 95% CI 1.44-4.47, P = 0.001). Lymph node metastases were more frequent in women with low expression of ASRGL1 compared with women with high ASRGL1 levels (23% versus 10%, P < 0.001), and low ASRGL1 level was found to independently predict lymph node metastases (odds ratio 2.07, 95% CI 1.27-3.38, P = 0.003). CONCLUSIONS: Low expression of ASRGL1 in curettage independently predicts lymph node metastases and poor disease-specific survival. TWEETABLE ABSTRACT: Low ASRGL1 expression in curettage predicts lymph node metastasis and poor survival in endometrial carcinoma.