Tissue microarray for protein profiling in non-small cell lung cancer (NSCLC):

Discovery and validation of novel biomarkers for prediction of recurrence and treatment response. Poster at International Association for the Study of Lung Cancer World Conference on Lung Cancer 2006

F. Robert, B.Z. Ring, R.S. Seitz, M.T. Schreeder, M. DeShazo, V.V.B. Reddy, R.B. Diasio, H. Ezzeldin, D.E. Carey, D-T. Chen., D.T. Ross
Applied Genomic Inc. (AGI), Sunnyvale, CA and Huntsville, AL, University of Alabama at Birmingham Comprehensive Cancer Center (UAB), Birmingham, AL, Comprehensive Institute of Huntsville (CCIH), Huntsville, AL.

Abstract

Background: Gene expression profiles have revealed biologically distinct groups of NSCLC with different clinical parameters and outcomes. AGI generated novel antibodies targeted by gene expression data to develop immunohistochemical (IHC) -based diagnostic tests stratifying NSCLC by histology, gender, smoking status, stage, sites of metastases and recurrent disease.

Methods: Several hundred novel affinity-purified rabbit anti-peptide antisera were screened by IHC for robust differential staining of NSCLC cases. A selected panel of 43 was tested on tissue arrays which contained more than 500 paraffin block cores from NSCLC tumor specimens. The first analysis was performed in 329 early stages cases with a mean follow-up of 3.3 years. Univariate analysis was used to identify reagents with an association with outcome. This subset of reagents was then used in Cox proportional hazard and regression tree analysis to build models for prediction of early recurrence. These predictor algorithms were validated by 10-fold crossvalidation and tested on independent set of 84 stage III/IV patients.

Results: Fifteen individual reagents showed an association with early or delayed recurrence (p<0.1). Algorithms using a panel of eight antibodies identified patients at high risk of recurrence in stage I/II patients (p<0.01). This algorithm was dependent upon first classifying patients as adenocarcinoma or squamous cell carcinoma. The predictive power of these models was confirmed on a cohort of stage III/IV patients at UAB (p<0.05).

Conclusions: Novel subtypes of NSCLC associated with poor outcome are distinguished by a panel of IHC antisera. These reagents should prove useful for patient stratification in care of early stage NCLSC. Further analysis in an expanded patient population with assessment of the epidermal growth factor receptor mutation status is ongoing.

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