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Drugs of interest to pathologists

Drugs related to surgical pathology

Erlotinib


Author: Him G. Kwee, M.D. (see Reviewers/Authors page)
Revised: 7 November 2011, last major update October 2011
Copyright: (c) 2011, PathologyOutlines.com, Inc.

General
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● Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
● The epidermal growth factor receptor (HER1/ErbB1) is a receptor tyrosine kinase of the ErbB family, which consists of 4 closely related receptors: HER1/ErbB1, HER2/neu/ErbB2, Her3/ErbB3 and HER4/ErbB4
● Upon ligand binding and receptor homo- or heterodimerization and activation (phosphorylation), activated EGFR signals downstream to the P13K/AKT and RAS, RAF and MAPK pathways
● These intracellular signaling pathways regulate key cellular processes such as proliferation and apoptosis (Mod Pathol 2008;21 Suppl 2:S16)

Trade name
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● Tarceva

Clinical information
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Approved by US Food and Drug Administration for:
● Locally advanced or metastatic non-small cell lung carcinoma
● Advanced, unresectable or metastatic pancreatic carcinoma

● Approximate cost: $2200 for 30 tablets of 100 mg, or $3100 for 30 tablets of 150 mg in 2011
● Another EGFR tyrosine kinase inhibitor, gefitinib (Iressa), was partially withdrawn by the FDA in the United States so that no new prescriptions can be made, but it remains in the market in Europe

Diagrams
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Signaling Pathway for EGFR


Use for pathologists
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● Since erlotinib is only used for adenocarcinoma and adenosquamous carcinoma (EGFR mutations are very rare in squamous cell carcinoma), the distinction between adenocarcinoma and squamous cell carcinoma in the lung is important
● Immunohistochemical stains for TTF1, napsinA, p63 and CK5/6 may be helpful to separate the two carcinomas; TTF1 and napsinA are specific for adenocarcinoma, and CK5/6 is specific for squamous cell carcinoma; p63 is sensitive for squamous cell carcinoma, but it can be positive in adenocarcinoma (Am J Surg Pathol 2011;35:15)
● Testing for EGFR mutation of the lung adenocarcinoma should be done by molecular analysis and not by immunohistochemistry
● Erlotinib is ineffective if the signaling pathway is activated by mutations downstream of EGFR, such as in KRAS and BRAF or if resistance mutations develop in EGFR (Mod Pathol 2008;21 Suppl 2:S16)
● If the tumor is small, attempts must be made to maximize the amount of diagnostic tissue for EGFR testing
● Lung adenocarcinomas with EGFR mutations are more predominant in women, Asians and non-smokers; its histologic pattern is predominantly lepidic, papillary or micropapillary and non-mucinous
● The less common mutation in lung adenocarcinoma, the KRAS mutation, is more common in non-Asians, smokers and mucinous adenocarcinoma (J Thorac Oncol 2011;6:244, Arch Pathol Lab Med 2011;135:1329)
● EGFR and KRAS mutations are virtually mutually exclusive

End of Drugs > Drugs related to surgical pathology > Erlotinib


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