Expression of ABC transporters, p53, Bax, Bcl-2 in an archival sample of non-small cell lung cancer bearing a deletion in the EGFR gene.
EGFR mutations have been correlated to responsiveness to treatment with tyrosine kinase inhibitors. These drugs are themselves substrates for ABC transporters. In the present work we describe the immunohistochemical profile of an archival sample from a male Brazilian patient with no Asian ancestry and never smoker, diagnosed with non-small cell lung cancer. This tumor was found to contain an in-frame hemi- or homozygous deletion, E746-A750 in exon 19 of the EGFR gene. Immunohistochemistry revealed a relatively weak staining for the ABC transporter subfamily ABCC1 and strongly for ABCB1. The cytoplasm stained positively for Bax and the nucleus stained for p53, but was negative for Bcl-2. Antibody against acetylated lysine revealed staining in both, cytoplasm and nucleus of tumor cells in contrast to normal cells which were essentially negative. The overall immunohistochemistry pattern obtained for this sample indicates that the del E746-A750 mutation may have down-regulated the expression of ABCC1. The results also suggest that the NSCLC analyzed displayed a transcriptionally active chromatin as judged by the results obtained with the anti-acetylated lysine antibody.
Amoêdo
Nivea Dias
ND
IInstituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Ilha do Fundão, CEP 21941-590, Rio de Janeiro, Brazil.
Castelo-Branco
Morgana Teixeira Lima
MT
Paschoal
Marcos Eduardo Machado
ME
Pezzuto
Paula
P
Esperança
Anna Beatriz Telles
AB
Rumjanek
Vivian M
VM
Rumjanek
Franklin David
FD
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D018070:Biological Specimen Banks; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000502:physiology; D018773:Genes, erbB-1; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D012189:Retrospective Studies; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D051028:bcl-2-Associated X Protein