title: Immunohistochemical overexpression of platelet-derived growth factor receptor-beta (PDGFR-β) is associated with PDGFRB gene copy number gain in sarcomatoid non-small-cell lung cancer.
abstract: Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We conducted immunohistochemical and fluorescence in situ hybridization studies of PDGF-B/PDGFR-b on archived surgically resected specimens and showed high PDGFR-b IHC expression and gene copy number gain. Further studies are warranted to determine whether PDGFR-b is a feasible therapeutic target in this population.
  
  
  BACKGROUND
  Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We hypothesized that the PDGF-B/PDGF-Rβ pathway may be dysregulated in sarcomatoid lung cancer.
  
  
  METHODS
  We conducted immunohistochemical (IHC) and gene copy number gain studies of PDGF-B/PDGFR-β on archived surgically resected specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and stage-matched. Biomarkers were correlated to patient demographics, tumor characteristics, and survival.
  
  
  RESULTS
  Sarcomatoid tumors had higher PDGFR-β IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No difference was seen between the two groups of PDGF-B IHC expression; and neither PDGF-B nor PDGFR-β IHC levels correlated with gender, age, clinical or pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated by FISH using three ways: presence of amplification, gene copy number gain, and gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013). Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher gene copy ratios above 1.83. Higher PDGFR-β IHC expression in tumor cells was associated with gene copy number gain (P = 0.021) and higher gene copy ratio status (P = 0.005).
  
  
  CONCLUSIONS
  This is the first study to demonstrate high PDGFR-β IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and suggests that further studies are warranted to determine whether PDGFR-β is a feasible therapeutic target in this population.
authors: Department of Thoracic and Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. astsao@mdanderson.org
authors: Anne S
authors: AS
authors: Tsao
authors: Wei
authors: W
authors: Wei
authors: Elisabetta
authors: E
authors: Kuhn
authors: Loreto
authors: L
authors: Spencer
authors: Luisa M
authors: LM
authors: Solis
authors: Milind
authors: M
authors: Suraokar
authors: J Jack
authors: JJ
authors: Lee
authors: Waun Ki
authors: WK
authors: Hong
authors: Ignacio I
authors: II
authors: Wistuba
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002296:Carcinosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D020797:Receptor, Platelet-Derived Growth Factor beta