title: Nestin: A biomarker of aggressive uterine cancers.
abstract: OBJECTIVE
  Evidence of potential prognostic and predictive value for nestin was investigated in well-annotated uterine cancers (UCs).
  
  
  METHODS
  Nestin expression and previously-published biomarkers were evaluated by immunohistochemistry (IHC) in UC tissue microarrays. Biomarkers were categorized as low vs. high, and nestin was cut at 10% positive staining. Relationship between nestin and clinicopathologic factors, biomarkers and outcome were evaluated using exact/log-rank testing or logistic/Cox modeling.
  
  
  RESULTS
  There were 323 eligible cases, 34% had advanced stage disease, 37% had type II disease, and 5% were carcinosarcomas. High nestin, observed in 19% of cases, was more common in advanced vs. early stage disease, type II cancers or uterine carcinosarcoma vs. type I cancers, grade 3 disease, positive lymphovascular space invasion (LVSI) and tumors >6cm (p<0.05). Nestin was inversely correlated with ER, PR and TFF3, and correlated with p53 and IMP3. Women with high vs. low nestin had worse progression-free survival (PFS) and cancer-specific survival overall, and worse PFS in the subset who received no adjuvant therapy or radiation, or had early stage, type I disease or tumors with both low and high ER, PR, TFF3, PTEN, p53 or IMP3. The relationship between nestin and PFS was independent of stage, LVSI and risk categorization but not type of UC.
  
  
  CONCLUSIONS
  High nestin was more common in UCs with aggressive features and poor outcome. Nestin may represent a predictive biomarker for treatment selection for patients previously considered to be lower risk and a candidate for no or radiation-based adjuvant therapy, and compliment ER/PR testing.
authors.affiliation: Walter Reed National Military Medical Center, Department of Obstetrics and Gynecology, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suites 370 and 375, Annandale, VA 22003, United States.
authors.forename: Erica R
authors.initials: ER
authors.lastname: Hope
authors.affiliation: University of Southern California, Department of Pathology, 1100 N. State Street, Los Angeles, CA 90033, United States.
authors.forename: Paulette
authors.initials: P
authors.lastname: Mhawech-Fauceglia
authors.affiliation: Oregon Health & Science University, Department of Obstetrics and Gynecology, 3181 SW Sam Jackson Park Road, L466, Portland, OR 97239, United States.
authors.forename: Tanja
authors.initials: T
authors.lastname: Pejovic
authors.affiliation: American College of Obstetricians and Gynecologists, 409 125th St. SW, Washington, DC 20024, United States; Uniformed Services University, Department of Obstetrics & Gynecology, 4301 Jones Bridge Road, Bethesda, MD 20814, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Zahn
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suites 370 and 375, Annandale, VA 22003, United States.
authors.forename: Guisong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suites 370 and 375, Annandale, VA 22003, United States; Uniformed Services University, Department of Obstetrics & Gynecology, 4301 Jones Bridge Road, Bethesda, MD 20814, United States; John P. Murtha Cancer Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suites 370 and 375, Annandale, VA 22003, United States; John P. Murtha Cancer Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Inova Fairfax Hospital, Department of Obstetrics & Gynecology, 3300 Gallows Road, Falls Church, VA 22042, United States.
authors.forename: G
authors.initials: G
authors.lastname: Larry Maxwell
authors.affiliation: Walter Reed National Military Medical Center, Department of Obstetrics and Gynecology, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suites 370 and 375, Annandale, VA 22003, United States; Uniformed Services University, Department of Obstetrics & Gynecology, 4301 Jones Bridge Road, Bethesda, MD 20814, United States; John P. Murtha Cancer Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suites 370 and 375, Annandale, VA 22003, United States; Uniformed Services University, Department of Obstetrics & Gynecology, 4301 Jones Bridge Road, Bethesda, MD 20814, United States; John P. Murtha Cancer Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States. Electronic address: DarcyK@WHIRC.org.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.affiliation: Uniformed Services University, Department of Obstetrics & Gynecology, 4301 Jones Bridge Road, Bethesda, MD 20814, United States; John P. Murtha Cancer Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States. Electronic address: viqar.syed@usuhs.edu.
authors.forename: Viqar
authors.initials: V
authors.lastname: Syed
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002296:Carcinosarcoma / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D064231:Nestin / Q000032:analysis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000032:analysis; D010455:Peptides / Q000032:analysis / Q000235:genetics; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D018570:Risk Assessment; D015996:Survival Rate; D046888:Tissue Array Analysis; D000071165:Trefoil Factor-3; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D064231:Nestin; D010455:Peptides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Biomarkers; Immunohistochemistry; Nestin; Predictive; Prognostic; TMA; Uterine cancer