EGFR, Lung Cancer and Cytology. Maureen F. Zakowski, M.D. Lung cancer is one of the most lethal cancers in Western countries and in Japan.
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1 EGFR, Lung Cancer and Cytology Maureen F. Zakowski, M.D. Lung cancer is one of the most lethal cancers in Western countries and in Japan. It is histopathologically divided into two major sub-groups: Small cell carcinoma and non small cell lung cancer (NSCLC). Adenocarcinoma makes up the largest subset of NSCLC in these countries, having replaced squamous cell carcinoma in the last decade or so. Women, patients with adenocarcinoma (as opposed to other types of NSCLC) of the lung, and never smokers with adenocarcinoma are more likely to have a favorable response to a new class of drugs called tyrosine kinase inhibitors (TKIs). Most of the patients who respond to these agents have a point mutation or deletion of amino acids from the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Treating cells carrying these alterations with TKIs leads to apoptosis and a G1/S arrest in the cell cycle. Tyrosine kinase activity is tightly regulated in normal cells, but is dysregulated due to mutations in some lung cancers, resulting in enhanced proliferation and survival of cancer cells. The tyrosine kinases are candidates for molecularly targeted therapy in cancer, because cancers become dependent on growth signals from the mutant tyrosine kinases. Tyrosine kinases require ATP for their enzymatic activity, and thus small molecules that mimic ATP can bind to mutant kinases and inactivate them. EGFR is a protein found on the surface of cells to which epidermal growth factor (EGF) binds. When EGF attaches to EGFR, it activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply. EGFR is found at abnormally high levels on the surface of many types of cancer cells, which may divide excessively in the presence of EGF. The drugs gefitinib (Iressa) and erlotinib (Tarceva) are TKIs that attach to EGFR and thereby inhibit the
2 attachment of EGF and stop cell division. The gene for EGFR is on chromosome 7. EGFR is also known confusingly as ErbB1, ErbB, oncogene ErbB, and HER1. The paradigm for tyrosine kinase inhibition as treatment for cancer using small-molecule inhibitors was first established in the context of chronic myelogenous leukemia (CML) associated with the BCR-ABL gene rearrangement. Imatinib (Gleevec) is a competitive inhibitor of ATP binding to the ABL kinase, thereby inhibiting the constitutively activated BCR-ABL tyrosine kinase. Imatinib induces complete remission in most patients with CML in stable phase, and also has activity in CML that has progressed to blast crisis. Imatinib is effective in treatment of chronic myelomonocytic leukemia with gene rearrangements and of gastrointestinal stromal cell tumors (GIST) associated with activating mutations in KIT. Several mutations have been identified in EGFR in patients with NSCLC that are associated with clinical response to the small-molecule EGFR inhibitors Iressa or Tarceva, including in-frame deletions such as del L747 E749;A750P in exon 19, or L858R in exon 21. Treatment with the EGFR kinase inhibitor Iressa causes tumor regression in some patients with NSCLC, more frequently in Japan than in the United States. Although the clinical and radiographic responses in these lung cancer patients are often dramatic, most responding patients ultimately develop clinical resistance and relapse of disease. The association of TKI therapy and EGFR mutations in lung cancer comes from the finding of such mutations in tumor samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was sensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggested that EGFR mutations may predict sensitivity to gefitinib. EGFR is often overexpressed on malignant cells, including 40 to 80 percent of patients with NSCLC. The factors that predicted the presence of EGFR mutations are the same factors that predict TKI responsiveness. Those include 40-50% of adenocarcinomas in Asia and 20% of adenocarcinomas in the USA, mostly in never smokers and in women, and often with a BAC
3 component. Mutations are exceedingly rare in squamous cell carcinoma (although they have been found in both components of adeno-squamous carcinoma) and large cell carcinoma. Mutations are present in >80% of tumors that respond to EGFR TKIs and are almost always absent in drug-refractory tumors. Mutations of EGFR are not found in association with KRAS mutations or in mucinous BACs (where KRAS is probably more common). Adenocarcinoma, and particularly adenocarcinoma with a BAC growth component, appears more susceptible to the TKIs. While this has been shown in a number of studies there is still confusion as to the morphologic characteristics of tumors that might predict sensitivity to these new small molecule agents. BAC, by WHO definition, cannot show invasion into lung, blood vessels, or pleura. This is a somewhat controversial definition that deviates from the original Liebow description. Because of this definition, it is commonly thought that cytology plays no role in the identification of BAC. This is not true. There are multiple studies that show features obvious in cytology that correspond to BAC or adenocarcinoma with a BAC component in subsequently resected material. These features include well differentiated appearance, intra nuclear grooves and inclusions, flat arrangements and monolayer sheets of cells. In terms of histomorphology, we found subtle, but rea, differences in the histopathology of responders to TKIs and non responders. The responders tended to be better differentiated adenocarcinomas showing less heterogeneity and more frequently had a BAC component. They also demonstrated little solid tumor growth and no necrosis. Papillary subtype was more frequent in the non responders. In terms of resistance of tumors to TKIs, there are both issues of primary resistance and secondary. Primary resistance is seen in tumors that are refractory to EGFR TKIs from the outset, and that is the majority of patients. The genetic predictors at diagnosis of this are KRAS mutations (common), EGFR mutations not sensitive to EGFR TKIs (rare, ~2%) and BRAF mutations (rare, ~3%). Secondary resistance is found in tumors that are initially sensitive to
4 EGFR TKIs but eventually progress while on therapy. In most cases, there are no good negative predictors, although histology plays a role. Most, if not all, secondary resistance is seen in initial responders and a second EGFR mutation has been identified in about 50% cases. Most of these cases are found to have a T790M or rarely, D761Y. More studies need to be done to better describe tumors that are responsive to TKI therapy to allow interpretation of histologic features of prognostic significance. However, in view of the fact that mutations are almost exclusively found in adenocarcinoma, we at Memorial Hospital have instituted reflex EGFR mutation testing of all surgically resected or sampled adenocarcinomas. At the time of grossing tissue is frozen and set aside on all lung tumors. If adenocarcinoma is identified at sign out, the frozen tumor is sent to our diagnostic molecular laboratory for determination of EGFR mutation status. PCR based assays are done for exon 19 deletions and exon 21 mutations; if these are negative sequencing for KRAS mutations is performed. If KRAS is found to be mutated TKIs are never given. These tests can also be done on archival paraffin embedded tissues, including cell blocks from cytology specimens. It is important to note that cell block material may often have a squamous appearance, even in cases of adenocarcinoma. This seems to be an artifact of processing. As non adenocarcinomas of the lung are not known to harbor EGFR mutations, misidentifying a tumor on cell block as squamous cell carcinoma can lead to the wrong therapy. Cell blocks, when enough tumor is present, are a better source for identifying EGFR mutations than other types of specimens such as Thin Preps, which may not be cellular enough. About 50% tumor is needed in a sample and non tumor tissue can be trimmed away without the need for laser micro dissection. FNA material can also be directly sent to the diagnostic molecular laboratory for analysis of EGFR, usually exons 19 and 21 and for KRAS as well. MSKCC used cytology material for a clinical trial. Patients were biopsied in the interventional radiology suite with a large bore needle. The core was rolled onto glass slides and stained with Diff Quik. When the diagnosis of adenocarcinoma was made, the remaining material was sent for
5 molecular analysis. The core roll served as the only source of diagnostic material pre operatively. After treatment with TKIs and surgery, the lung tumors were again studied for EGFR. There was perfect concordance in mutation identification done on the cytology diagnosed tissue and the surgically resected tissue. We have also begun keeping a tumor bank of cytology material. When Thin Preps are particularly cellular, multiple slides are made and keep uncovered and frozen as a potential source for future studies. EGFR mutation status plays a large role in the determination of new targeted therapies against adenocarcinoma, but the role of histology and cytology remain vital in identifying features that might indicate the need for testing and to select cases for treatment with TKIs in the absence mutations information. Take Home Points The distinction between adenocarcinoma and squamous cell carcinoma is critical in the management of lung cancer patients and must be made in cytologic material as well as histologic Adenocarcinoma, particularly with BAC features, may harbor TKI sensitizing EGFR mutations BAC features can be recognized in cytologic material Molecular analysis for EGFR can be done on cytologic material
6 Reference Hirsch FR, Varella-Garcia M, Bunn PA, Jr., et al. Epidermal growth factor receptor in nonsmall-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003; 21(20): Hirsch FR, Witta S. Biomarkers for prediction of sensitivity to EGFR inhibitors in nonsmall cell lung cancer. Curr Opin Oncol. 2005;17(2): Jemal A, Murray T, Ward E, et al. Cancer statistics, CA Cancer J Clin. 2005;55(1): Kosaka T, Yatabe Y, Endoh H, et al. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004; 64(24): Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004; 350(21): Marchetti A, Buttitta F, Pellegrini S, et al. Bronchioloalveolar lung carcinomas: K-ras mutations are constant events in the mucinous subtype. J Pathol. 1996; 179(3): Marchetti A, Martella C, Felicioni L, et al. EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol. 2005;23(4): Miller VA, Johnson DH, Krug LM, et al. Pilot trial of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib plus carboplatin and paclitaxel in patients with stage IIIB or IV non-small-cell lung cancer. J Clin Oncol. 2003; 21(11): Miller VA, Kris MG, Shah N, et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol. 2004; 22(6): Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304(5676): Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004; 101(36): Pao W, Miller VA. Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J Clin Oncol. 2005; 23(11): Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005; 2(1):e17.. Pao W, Zakowski MF, Cordon-Cardo C, et al. Molecular characteristics of non-small cell lung cancer (NSCLC) patients sensitive to gefitinib (Iressa ). Proc ASCO Annual Meeting, Abstract No
7 Parra HS, Cavina R, Latteri F, et al. Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa', ZD1839) in non-smallcell lung cancer. Br J Cancer. 2004; 91(2): Rusch VW, Reuter VE, Kris MG, et al. Ras oncogene point mutation: an infrequent event in bronchioloalveolar cancer. J Thorac Cardiovasc Surg. 1992; 104(5): Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005; 97(5): Suzuki S, Dobashi Y, Sakurai H, et al. Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas. Cancer. 2005; 103(6): Swinson DE, Cox G, O'Byrne KJ. Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer. Br J Cancer. 2004; 91(7): Tokumo M, Toyooka S, Kiura K, et al. The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res. 2005; 11(3): Liebow AA. Bronchiolo-alveolar carcinoma. Adv Intern Med. 1960;10:
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