title: Tumoral CD10 expression correlates with high-grade histology and increases risk of recurrence in patients with stage I lung adenocarcinoma.
abstract: OBJECTIVE
  CD10 (neutral endopeptidase) is expressed in various normal and tumor cells, and its biological function can be controlled through enzymatic activity and signaling pathways. We investigated whether CD10 expression predicted disease recurrence and whether it correlated with histologic subtypes of stage I lung adenocarcinoma.
  
  
  METHODS
  We reviewed tumor slides of resected pathologic stage I lung adenocarcinomas (1995-2009). Tumors were classified according to the IASLC/ATS/ERS classification. CD10 immunohistochemistry was performed using tissue microarrays (n=915). We combined the intensity (0-3) and distribution scores (0-2) for CD10 to create a total score (0-5). Risk of recurrence was estimated using competing risks methods.
  
  
  RESULTS
  In the training cohort (n=313), risk of recurrence of patients with high tumoral CD10 (score>1, n=57) was significantly higher (5-year cumulative incidence of recurrence [CIR], 37%) than in those with low CD10 (score≤1; n=256; 5-year CIR, 16%; P<0.001); this finding was confirmed in the validation cohort (n=602, P=0.036). High tumoral CD10 was associated with higher risk of recurrence in acinar (P=0.007) and papillary predominant tumors (P=0.022). High tumoral CD10 was most frequently identified in micropapillary predominant (41%) and solid predominant tumors (34%). On multivariate analysis of intermediate-grade tumors, high tumoral CD10 remained a significant independent risk factor of recurrence (hazard ratio, 1.88; P=0.025).
  
  
  CONCLUSIONS
  In stage I lung adenocarcinoma, tumoral CD10 correlated with high-grade histology and was an independent predictor of recurrence in intermediate-grade tumors.
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Buitrago
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Institute of Clinical Medicine; National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Villena-Vargas
authors.affiliation: Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, United States. Electronic address: adusumip@mskcc.org.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015260:Neprilysin
keywords: Adenocarcinoma; CD10; Histology; Lung; Recurrence