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
Presented at the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 2628, 2004.
BACKGROUND: Overexpression of squamous cell carcinomarelated oncogene (SCCRO) is associated with invasive progression and poor outcomes in nonsmall 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 carcinomarelated 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 carcinomarelated 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 carcinomarelated 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 hosttumor effects.
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