Your browser doesn't support javascript.
loading
Asparaginase-like protein 1 as a prognostic tissue biomarker in clinicopathologically and molecularly characterized endometrial cancer.
Loukovaara, Mikko J; Huvila, Jutta K; Pasanen, Annukka M; Bützow, Ralf C.
Affiliation
  • Loukovaara MJ; Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address: mikko.loukovaara@hus.fi.
  • Huvila JK; Department of Biomedicine, University of Turku, Turku University Hospital, Turku, Finland. Electronic address: jkvuor@utu.fi.
  • Pasanen AM; Department of Pathology, Helsinki University Hospital and Research Program in Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: annukka.pasanen@hus.fi.
  • Bützow RC; Department of Pathology and Department of Obstetrics and Gynecology, Helsinki University Hospital and Research Program in Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: ralf.butzow@hus.fi.
Eur J Obstet Gynecol Reprod Biol ; 300: 23-28, 2024 Jul 04.
Article de En | MEDLINE | ID: mdl-38972163
ABSTRACT

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.
Mots clés

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Langue: En Journal: Eur J Obstet Gynecol Reprod Biol Année: 2024 Type de document: Article

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Langue: En Journal: Eur J Obstet Gynecol Reprod Biol Année: 2024 Type de document: Article