title: Synuclein-γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study.
abstract: Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023).
  
  
  
  High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression-free survival were assessed using log-rank tests and Cox proportional-hazards models, which also were adjusted for age, race, and stage.
  
  
  
  The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log-rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91-1.9 in adjusted Cox model). The progression-free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log-rank P = .0081; HR, 1.36; 95% CI, 0.96-1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54-11.45]; p16: HR, 1.95 [95% CI, 1.01-3.75]) and progression-free survival (p53: HR, 2.16 [95% CI, 1.09-4.27]; p16: HR, 1.53 [95% CI, 0.87-2.69]) compared with low levels.
  
  
  
  This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144-1155. © 2016 American Cancer Society.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois.
authors.forename: Abigail D
authors.initials: AD
authors.lastname: Winder
authors.affiliation: Division of Surgical Pathology, Department of Pathology, Northwestern University, Chicago, Illinois.
authors.forename: Kruti P
authors.initials: KP
authors.lastname: Maniar
authors.affiliation: Division of Surgical Pathology, Department of Pathology, Northwestern University, Chicago, Illinois.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
authors.affiliation: Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Dachao
authors.initials: D
authors.lastname: Liu
authors.affiliation: Division of Biostatistics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Scholtens
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois.
authors.forename: John R
authors.initials: JR
authors.lastname: Lurain
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Spectrum Health, Grand Rapids, Michigan.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Schink
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Buttin
authors.affiliation: Statistics and Data Management Center, NRG Oncology, Buffalo, New York.|Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Filiaci
authors.affiliation: Statistics and Data Management Center, NRG Oncology, Buffalo, New York.|Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
authors.affiliation: Biopathology Center and Gynecologic Oncology Group Tissue Bank, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Nilsa C
authors.initials: NC
authors.lastname: Ramirez
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Kay
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Pathology, University of Kansas School of Medicine and Medical Center, Kansas City, Kansas.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.|Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Lieberman
authors.affiliation: Department of Gynecologic Oncology, The Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.affiliation: Division of Gynecologic Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Powell
authors.affiliation: Division of Gynecologic Oncology, Ohio State University and James Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Floor J
authors.initials: FJ
authors.lastname: Backes
authors.affiliation: Division of Obstetrics and Gynecology, Women and Infants Hospital, Providence, Rhode Island.
authors.forename: Cara A
authors.initials: CA
authors.lastname: Mathews
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Medicine, Stony Brook University Medical Center, Stony Brook, New York.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Pearl
authors.affiliation: Department of Obstetrics/Gynecology, Division of Gynecology Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Angeles Alvarez
authors.initials: AA
authors.lastname: Secord
authors.affiliation: Division of Hematology/Oncology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois.
authors.forename: David J
authors.initials: DJ
authors.lastname: Peace
authors.affiliation: Division of Gynecologic Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: William T
authors.initials: WT
authors.lastname: Creasman
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois.
authors.forename: J Julie
authors.initials: JJ
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D051845:gamma-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051845:gamma-Synuclein
keywords: endometrial cancer; p16; p53; synuclein-γ (SNCG); uterine serous carcinoma