Cytologic features associated with BAC were not identified with this specimen. EGFR Status in Responders A total of 22 (75%) of 29 responders had mutations. were not significantly correlated with mutations or response to TKIs with this study. Conclusions Overall, histologic differences exist between tumors that respond to TKIs and those that do not, although sampling affects classification, and there is significant histologic overlap between the 2 groups. Response is definitely strongly associated with mutations. Lung malignancy remains the best cause of tumor death in the United States and worldwide in both men and women.1 The treatment of nonCsmall cell lung cancer (NSCLC) has recently expanded beyond surgery and standard 3,4-Dihydroxymandelic acid chemotherapy with the identification of tumors responsive to tyrosine kinase inhibitors (TKIs). Histopathology, along with careful clinical/molecular correlation, takes on a critical part in the selection of individuals most likely to respond to these fresh small molecule providers. We have previously demonstrated2 that among NSCLCs, adenocarcinoma, and, interestingly, the subtype adenocarcinoma with bronchioloalveolar carcinoma (BAC) features, appear preferentially susceptible to the effects of the TKI gefitinib (Iressa, AstraZeneca, Wilmington, Del). A similar Ncam1 agent, erlotinib (Tarceva, Genentech, South San Francisco, Calif), has also been used with success against the same spectrum of lung carcinomas. Adenocarcinoma with BAC features corresponds to the World 3,4-Dihydroxymandelic acid Health Corporation (WHO) classification of adenocarcinoma, combined subtype having a BAC component. The epidermal growth element receptor (EGFR) is definitely a member of a family of transmembrane glycoproteins that includes HER-2, HER-3, and HER-4 that functions like a receptor tyrosine kinase and is present on and is commonly overexpressed in most NSCLCs. Overexpression in NSCLC ranges from about 40% to 90%. Variations in manifestation may relate to variations in assessment techniques, definition of level of overexpression, and variations in the study populations.3 Providers that interfere with phosphorylation of critical tyrosine residues can block transmission transduction through EGFR. Gefitinib and erlotinib are such providers. The US Food and Drug Administration authorized gefitinib in 2003 as targeted monotherapy for the treatment of individuals with locally advanced or metastatic NSCLC. Use of this drug was subsequently restricted when a trial in lung malignancy individuals failed to display a benefit.4 Erlotinib received authorization in 2004 and is commonly used in NSCLC individuals. We undertook the characterization of the morphologic features of lung adenocarcinomas in individuals who showed response to gefitinib and erlotinib by analyzing tissues acquired for histologic or cytologic analysis prior to initiation of therapy. Our goal was to identify pathologic features among adenocarcinomas that 3,4-Dihydroxymandelic acid are predictive of response to these providers. In light of the recently reported recognition of specific activating mutations in the EGFR TK website underlying responsiveness of NSCLC to gefitinib and erlotinib,5C7 the acknowledgement of morphologic features predictive of treatment response might lead to better understanding of the connection of tumor histology and genotype, and might result in more successful targeted therapy. MATERIALS AND METHODS Case Selection We analyzed tumor material from 52 individuals treated with erlotinib or gefitinib on institutional review boardCapproved protocols. These included 29 instances of adenocarcinoma of the lung from individuals treated with gefitinib (n = 18) or erlotinib (n = 11) who showed response relating to Response Evaluation Criteria In Solid Tumors8 and who experienced cytologic or histologic material available for review. Briefly, Response Evaluation Criteria In Solid Tumors defines partial response in tumor shrinkage as at least a 30% decrease in the sum of the longest diameter of the prospective lesions. The Response Evaluation Criteria In Solid Tumors recommendations were developed to derive response rates from unidimensional measurement of tumor.