title: The incidence of EGFR-activating mutations in bone metastases of lung adenocarcinoma.
abstract: Poor prognosis of lung adenocarcinoma is associated with early occurrence of distant metastases. This type of non-small-cell lung carcinoma more frequently involves EGFR gene abnormalities, which determine the efficacy of EGFR tyrosine kinase inhibitor therapies (EGFR TKIs). It is probable that genetic abnormalities present in primary tumor will also be present in metastases. Unfortunately little is known about the incidence of these mutations in the metastases and about the effectiveness of molecularly targeted therapy in such patients. Formalin-fixed, paraffin-embedded tumor tissue was prepared from 431 samples of primary adenocarcinoma, 61 of adenocarcinoma central nervous system (CNS) metastases and 8 of adenocarcinoma bone metastases. The presence of exon 19 deletions was examined using the PCR technique and amplified PCR product fragment length analysis. The ASP-PCR technique was used to evaluate the L858R substitutions in exon 21, and the results were analyzed using ALF Express II sequencer. In the adenocarcinoma metastases to bone obtained from 8 patients, deletions in exon 19 of the EGFR gene were revealed in 3 smoking men and one non-smoking woman, while L858R substitution in exon 21 was found in one smoking woman and one man of unknown smoking status. The incidence of EGFR gene mutations in the bone metastases was 75%, in the primary adenocarcinoma--12.8%, and in the adenocarcinoma metastases to CNS--14.75%. Five patients with EGFR gene mutation revealed in bone metastases were treated with EGFR TKIs; the majority of them had a satisfactory response to therapy.
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland, krapa@poczta.onet.pl.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.forename: Marcin
authors.initials: M
authors.lastname: Nicoś
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Tomasz
authors.initials: T
authors.lastname: Powrózek
authors.forename: Kamila
authors.initials: K
authors.lastname: Wojas-Krawczyk
authors.forename: Sylwia
authors.initials: S
authors.lastname: Sura
authors.forename: Bożena
authors.initials: B
authors.lastname: Jarosz
authors.forename: Justyna
authors.initials: J
authors.lastname: Szumiło
authors.forename: Edward
authors.initials: E
authors.lastname: Warda
authors.forename: Tomasz
authors.initials: T
authors.lastname: Mazurkiewicz
authors.forename: Marek
authors.initials: M
authors.lastname: Sawicki
authors.forename: Janusz
authors.initials: J
authors.lastname: Milanowski
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012907:Smoking / Q000235:genetics
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors