[1637] ERK Immunostaining Predicts EGFR and/or KRAS Mutation in Lung Adenocarcinomas, and Can Be Used To Prescreen Tumors for Subsequent Molecular Testing

MB Ruzinova, V Joshi, D Jackman, P Janne, NI Lindeman. Brigham and Women's Hospital, Boston, MA; Beigham and Women's Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA

Background: Somatic mutations in the gene for the epidermal growth factor receptor (EGFR) are found in 20% of lung adenocarcinomas and are associated with clinical response to the tyrosine kinase inhibitors (TKIs) gefitinib (Iressa) and erlotinib (Tarceva). Another 30% of lung adenocarcinomas harbor activating mutations in KRAS, the GTPase involved in signaling downstream of EGFR, but in contrast to EGFR mutations, KRAS mutations confer resistance to TKIs. Molecular analysis of both genes is needed to guide TKI therapy, but molecular analysis is costly and not widely available, and a simpler technique is desirable. Since both EGFR and KRAS mutations lead to increased levels of a common downstream effector, extracellular signal regulated kinase (ERK), IHC for ERK may be useful to select tumors to refer for molecular testing.
Design: ERK expression was studied by immunohistochemistry on a microarray containing 5 cores from each of 29 lung adenocarcinomas, and correlated with the mutational status of EGFR and KRAS determined by direct sequencing of corresponding tissue from dissected unstained 5-micron paraffin-sections.
Results: ERK immunoreactivity was seen in 15/20 (75% sensitivity) tumors with either EGFR or KRAS mutation, and in only 3/9 tumors without mutation in either gene (67% specificity). Positive predictive value in this selected population was 83.3% (15/18) . All three of the patients with ERK positivity but neither EGFR nor KRAS mutation failed to respond to TKI treatment, suggesting that perhaps an alteration in another signaling molecule downstream of KRAS (e.g., BRAF) may be the oncogenic stimulus in these tumors.
Conclusions: ERK immunostaining may be a useful predictive tool to identify tumors that have mutations in either EGFR or KRAS, and should go on to molecular testing of these genes. Larger studies are needed to confirm this result.
Category: Pulmonary

Tuesday, March 10, 2009 1:00 PM

Poster Session IV # 235, Tuesday Afternoon