Which of the following is NOT a known predictive or prognostic tumor marker for adenocarcinoma?
A. EGFREstablishing a clear histologic diagnosis early in the evaluation and management of lung cancer is critical to effective treatment. Molecular signatures are also key determinants of treatment algorithms for adenocarcinoma and will likely become important for squamous cell carcinoma as well. Currently, differentiation between adenocarcinoma and squamous cell carcinoma in cytologic specimens or small biopsy specimens is imperative in patients with advanced stage disease, as treatment with pemetrexed or bevacizumab-based chemotherapy is associated with improved progression-free survival in patients with adenocarcinoma but not squamous cell cancer. Furthermore, life-threatening hemorrhage has occurred in patients with squamous cell carcinoma who were treated with bevacizumab. Finally, EGFR mutation predicts response to EGFR tumor kinase inhibitors and is now recommended as first-line therapy in advanced adenocarcinoma. Because adequate tissue is required for histologic assessment and molecular testing, each institution should have a clear, multidisciplinary approach to patient evaluation, tissue acquisition, tissue handling/processing, and tissue analysis. In many cases, tumor morphology differentiates adenocarcinoma from the other histologic subtypes. If no clear morphology can be identified, then additional testing for one immunohistochemistry marker for adenocarcinoma and one for squamous cell carcinoma will usually enable differentiation. Immunohistochemistry for neuroendocrine markers is reserved for lesions exhibiting neuroendocrine morphology. Additional molecular testing should be performed on all adenocarcinoma specimens for known predictive and prognostic tumor markers ( eg, EGFR, KRAS, and EML4-ALK fusion gene). Ideally, use of tissue sections and cell block material is limited to the minimum necessary at each decision point. This emphasizes the importance of a multidisciplinary approach; surgeons and radiologists must work in direct cooperation with the cytopathologist to ensure that tissue samples are adequate for morphologic diagnosis as well as providing sufficient cellular material to enable molecular testing.