title: SCCRO expression correlates with invasive progression in bronchioloalveolar carcinoma.
abstract: BACKGROUND
  Overexpression of squamous cell carcinoma-related oncogene (SCCRO) is associated with invasive progression and poor outcomes in non-small cell lung cancer. We assessed the role of SCCRO as a tumor marker in bronchioloalveolar carcinoma (BAC), a subtype of adenocarcinoma exhibiting evidence of histologic tumor progression. We hypothesized that SCCRO expression would correlate with invasive tumor phenotypes and worse survival in BAC.
  
  
  METHODS
  We classified 150 tumors as pure BAC, BAC with focal invasion, or adenocarcinoma with BAC features. A tissue microarray was constructed from areas of benign lung, BAC, and invasive adenocarcinoma in these tumors. Squamous cell carcinoma-related oncogene expression was graded by immunohistochemistry from 0 to 3 (absent, low, moderate, or high), with positive SCCRO phenotype defined as grade 3. Squamous cell carcinoma-related oncogene specificity was determined by Wilcoxon rank test and area under the receiver-operator curve, survival by the Kaplan-Meier method, and correlation with prognostic factors by log-rank test.
  
  
  RESULTS
  Of the 86.0% (129 of 150) of specimens suitable for analysis, positive SCCRO phenotype was seen in 16.3% (21 of 129) and was 100.0% specific for tumor versus benign tissue (area under receiver-operator curve, 0.92). Positive SCCRO phenotype was greater in tumors with increasing degrees of invasive histologic type (7.0% pure BAC, 13.6% BAC with focal invasion, and 28.6% adenocarcinoma with BAC features; p = 0.02). Low-level SCCRO expression was present in 83.9% (99 of 118) of benign tissues and correlated with tobacco use and poor survival (p = 0.05).
  
  
  CONCLUSIONS
  Squamous cell carcinoma-related oncogene is a marker of invasive tumor progression in BAC. Low-level expression in adjacent benign lung predicts worse survival, and may represent field cancerization or host-tumor effects.
authors.affiliation: Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Sarkaria
authors.forename: DuyKhanh
authors.initials: D
authors.lastname: Pham
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Ghossein
authors.forename: Simon G
authors.initials: SG
authors.lastname: Talbot
authors.forename: Michael
authors.initials: M
authors.lastname: Hezel
authors.forename: Maria E
authors.initials: ME
authors.lastname: Dudas
authors.forename: Michael I
authors.initials: MI
authors.lastname: Ebright
authors.forename: Shaokun
authors.initials: S
authors.lastname: Chuai
authors.forename: Natalie
authors.initials: N
authors.lastname: Memoli
authors.forename: Ennapadam S
authors.initials: ES
authors.lastname: Venkatraman
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D015993:Life Tables; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D010641:Phenotype; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D012907:Smoking; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins