title: The expression of p-STAT3 in stage IV melanoma: risk of CNS metastasis and survival.
abstract: OBJECTIVE
  The signal transducer and activator of transcription 3 (STAT3) is a key molecular hub of tumorigenesis and immune suppression. The expression of phosphorylated STAT3 (p-STAT3) has been shown to be higher in melanoma metastasis to the central nervous system (CNS) relative to distant metastasis in the rest of the body (systemic). We sought to determine whether the increased expression of p-STAT3 in non-CNS systemic melanoma metastasis is associated with an increased risk of developing CNS metastasis and is a negative prognostic factor for overall survival time.
  
  
  METHODS
  We retrospectively identified 299 patients with stage IV melanoma. In a tissue microarray of systemic non-CNS metastasis specimens from these patients, we used immunohistochemical analysis to measure the percentage of cells with p-STAT3 expression and Kaplan-Meier survival estimates to analyze the association of p-STAT3 expression with median survival time, time to first CNS metastasis, and development of CNS metastasis.
  
  
  RESULTS
  Lung metastases exhibited the highest level of p-STAT3 expression while spleen lesions had the lowest. The p-STAT3 expression was not associated with an increased risk of developing CNS metastasis or time to CNS metastasis. However, p-STAT3 expression was a negative prognostic factor for overall survival time in patients that did not develop CNS metastasis.
  
  
  CONCLUSIONS
  Stage IV melanoma patients without CNS metastasis treated with p-STAT3 inhibitors in efficacy studies should be stratified based on tumor expression of p-STAT3; however since p-STAT3 expression is not associated with the risk of CNS disease, increased MRI surveillance of the brain is not likely necessary.
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Lee
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Fox
authors.forename: Sherise D
authors.initials: SD
authors.lastname: Ferguson
authors.forename: Roland
authors.initials: R
authors.lastname: Bassett
authors.forename: Ling-Yuan
authors.initials: LY
authors.lastname: Kong
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Schacherer
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grimm
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human