Per-Henrik D Edqvist1, Jutta Huvila2, Björn Forsström3, Lauri Talve4, Olli Carpén5, Helga B Salvesen6, Camilla Krakstad7, Seija Grénman8, Henrik Johannesson9, Oscar Ljungqvist9, Mathias Uhlén3, Fredrik Pontén10, Annika Auranen8. 1. Uppsala University, Department of Immunology, Genetics and Pathology, Sweden; Science for Life Laboratory, Uppsala, Sweden. Electronic address: Per-henrik.edqvist@igp.uu.se. 2. 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. 3. Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden. 4. Department of Pathology, Turku University Hospital, Turku, Finland. 5. Department of Pathology, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital, Turku, Finland. 6. Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway. 7. Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway. 8. Department of Gynecology and Obstetrics, University of Turku, Turku, Finland; Department of Gynecology and Obstetrics, Turku University Hospital, Turku, Finland. 9. Atlas Antibodies AB, AlbaNova University Center, 106 91 Stockholm, Sweden. 10. Uppsala University, Department of Immunology, Genetics and Pathology, Sweden; Science for Life Laboratory, Uppsala, Sweden.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Elena A Pudova; Elena N Lukyanova; Kirill M Nyushko; Dmitry S Mikhaylenko; Andrew R Zaretsky; Anastasiya V Snezhkina; Maria V Savvateeva; Anastasiya A Kobelyatskaya; Nataliya V Melnikova; Nadezhda N Volchenko; Gennady D Efremov; Kseniya M Klimina; Anastasiya A Belova; Marina V Kiseleva; Andrey D Kaprin; Boris Y Alekseev; George S Krasnov; Anna V Kudryavtseva Journal: Front Genet Date: 2019-08-09 Impact factor: 4.599
Authors: Patrick Micke; Carina Strell; Johanna Mattsson; Alfonso Martín-Bernabé; Hans Brunnström; Jutta Huvila; Malin Sund; Fredrik Wärnberg; Fredrik Ponten; Bengt Glimelius; Ina Hrynchyk; Siarhei Mauchanski; Salome Khelashvili; Gemma Garcia-Vicién; David G Molleví; Per-Henrik Edqvist; Aine O Reilly; Sara Corvigno; Hanna Dahlstrand; Johan Botling; Ulrika Segersten; Agnieszka Krzyzanowska; Anders Bjartell; Jacob Elebro; Margareta Heby; Sebastian Lundgren; Charlotta Hedner; David Borg; Jenny Brändstedt; Hanna Sartor; Per-Uno Malmström; Martin Johansson; Björn Nodin; Max Backman; Cecilia Lindskog; Karin Jirström; Artur Mezheyeuski Journal: EBioMedicine Date: 2021-03-08 Impact factor: 8.143