SCCRO expression correlates with invasive progression in bronchioloalveolar carcinoma.
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.
Sarkaria
Inderpal S
IS
Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Pham
DuyKhanh
D
Ghossein
Ronald A
RA
Talbot
Simon G
SG
Hezel
Michael
M
Dudas
Maria E
ME
Ebright
Michael I
MI
Chuai
Shaokun
S
Memoli
Natalie
N
Venkatraman
Ennapadam S
ES
Miller
Vincent A
VA
Kris
Mark G
MG
Zakowski
Maureen F
MF
Rusch
Valerie W
VW
Singh
Bhuvanesh
B
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
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins