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Ann Thorac Surg 2004;78:1734-1741
© 2004 The Society of Thoracic Surgeons
a Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
b Department of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
c Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
d Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
e Department of Thoracic Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
f Department of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Accepted for publication May 17, 2004.
* Address reprint requests to Dr Singh, Memorial Sloan-Kettering Cancer Center, Head and Neck Surgery, 1275 York Ave, New York, NY 10021, USA
singhb{at}mskcc.org
Presented at the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 26–28, 2004.
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.
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