title: Expression of activated and latent signal transducer and activator of transcription 3 in 303 non-small cell lung carcinomas and 44 malignant mesotheliomas: possible role for chemotherapeutic intervention.
abstract: BACKGROUND
  Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse human cancers and plays a critical role in tumor cell survival, proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis. The phosphorylated active form of STAT3 (pSTAT3) mediates its effects via nuclear transcriptional activity. However, it was recently observed that the nonphosphorylated, cytoplasmic, inactive form of STAT3 is involved in cell motility and consequently tumor invasion. It appears that, although STAT3 is not absolutely required for tumor formation, tumors that develop in the presence of STAT3 become dependent on its expression for their survival, making it a potential therapeutic target.
  
  
  OBJECTIVE
  To investigate the possible utility of STAT3 as a future therapeutic target in non-small cell lung carcinoma (NSCLC) and malignant mesothelioma (MM).
  
  
  METHODS
  Immunohistochemical expression of MIB-1, STAT3, and pSTAT3 was assessed in 303 NSCLC and 44 MM archival cases.
  
  
  RESULTS
  A more conspicuous expression of inactive STAT3 (91.44% in NSCLC and 79.5% in MM cases) was present compared with the nuclear activated form pSTAT3 (60.53% in NSCLC and 61.4% in MM cases). MIB-1 did not correlate with the expression of STAT3 or pSTAT3.
  
  
  CONCLUSIONS
  The strong expression of cytoplasmic inactive STAT3 in NSCLC and MM cases implies a major role for STAT3 in tumor motility, invasion, and metastasis via a nontranscriptional pathway. We conclude that STAT3 and pSTAT3 are up-regulated in a high percentage of NSCLCs and MMs, regardless of tumor type, age, sex, smoking status, stage and grade of tumor, or survival, providing a basis for therapeutic intervention.
authors.affiliation: Department of Pathology, University of Texas Health Sciences Center, San Antonio, USA.
authors.forename: Rosane de Oliveira Duarte
authors.initials: Rde O
authors.lastname: Achcar
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.forename: Jaishree
authors.initials: J
authors.lastname: Jagirdar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*