title: Epidermal growth factor receptor, C-kit, and Her2/neu immunostaining in advanced or recurrent thymic epithelial neoplasms staged according to the 2004 World Health Organization in patients treated with octreotide and prednisone: an Eastern Cooperative Oncology Group study.
abstract: BACKGROUND
  Advanced or recurrent nonresectable thymic epithelial tumors show only a modest response to standard chemotherapy. A recent study using octreotide and prednisone in thymic tumors, Eastern Cooperative Oncology Group study E1C97, was conducted to verify the activity of octreotide for thymic tumors. The aim of this study was to determine whether epidermal growth factor receptor (EGFR) immunoreactivity correlated with outcomes and to identify new biologic markers for potential targeted therapy. Three markers, EGFR, C-kit, and Her2/neu, were selected for evaluation in patients with advanced thymic epithelial tumors treated on E1C97.
  
  
  METHODS
  Of the 42 patients entered onto E1C97, 34 patients (World Health Organization [WHO] categories: type A = 1, type AB = 1, type B1 = 10, type B2 = 11 type B3 = 8, and type C = 3) had sufficient tissue available for immunohistologic study. Each tumor was assessed to have 0, 1+, 2+, or 3+ immunoreactivity in the cytoplasm or membranes of the neoplastic cells for Her2/neu and EGFR and for the presence or absence of C-kit immunoreactivity.
  
  
  RESULTS
  EGFR immunoreactivity of 2+ or 3+ was associated with more aggressive thymic tumors (WHO types B2 and B3). However, strong EGFR immunoreactivity was not consistently seen with thymic carcinoma. The presence of EGFR within cells was associated with a significantly improved progression-free survival (PFS) and a trend for overall survival (OS). Twelve patients demonstrated C-kit immunoreactivity; the lack of C-kit immunoreactivity was significantly associated with superior PFS but not OS. Her2/neu immunoreactivity was uniformly negative for all tumors evaluated. There was no association between response and biomarker status.
  
  
  CONCLUSIONS
  High EGFR immunoreactivity is seen in more aggressive thymic neoplasms as classified according to the 2004 WHO, but regardless of classification, the presence of EGFR in tumor cells (1+, 2+, and 3+) is associated with improved performance free survival (PFS) and a trend for better OS. In contrast, the absence of C-kit immunoreactivity was associated with improved PFS. These data suggest that EGFR and C-kit may be prognostic, and further studies of these markers in subcategories of thymic malignancies is warranted.
authors.affiliation: Department of Pathology, UMDNJ-NJMS, Newark, New Jersey, USA. aisnersc@verizon.net
authors.forename: Seena C
authors.initials: SC
authors.lastname: Aisner
authors.forename: Suzanne
authors.initials: S
authors.lastname: Dahlberg
authors.forename: Meera R
authors.initials: MR
authors.lastname: Hameed
authors.forename: David S
authors.initials: DS
authors.lastname: Ettinger
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
authors.forename: Joseph
authors.initials: J
authors.lastname: Aisner
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Loehrer
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015282:Octreotide / Q000008:administration & dosage*; D011241:Prednisone / Q000008:administration & dosage*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D013953:Thymus Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014944:World Health Organization
chemical_list: D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D015282:Octreotide; D011241:Prednisone; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human