Relationship of p53 molecular abnormalities with flow cytometry and growth factor receptor content in lung cancer.
This study attempts of clarify the oncological significance of the p53 molecular abnormalities and p53 expression in lung cancer (LC) and their relationship with flow cytometry (FC) parameters and epidermal growth factor receptor (EGFR). The study includes 65 samples taken from both LC and normal lung (NL). The p53 molecular abnormalities of exons 4-8 were studied by single strand conformation polymorphisms (SSCP) and the loss of heterozygosity (LOH) of exon 4 by the Metzler method. P53 protein was detected by Western blot. EGFR was determined by a radioligand assay using [125I]EGF. The FC parameters S phase fraction (SPF), DNA index (D.I.), G1G0 and growth rate (G2M + SPF) were evaluated from cellular monosuspensions. The LC with SSCP p53 molecular abnormalities have a significantly higher EGFR content (P < 0.001), SPF (P < 0.007), D.I. (P < 0.017) and a lower proportion of G1G0 cells (P < 0.04) than LC with no molecular abnormalities. No relationship between p53 molecular abnormalities and tumor TN or evolutive events was found. Neither the relationship between the molecular results and p53 expression detected by Western blot nor that of the p53 expression detected by Western with FC parameters or EGFR could be shown. In NL the growth fraction cells decrease significantly (P < 0.05) with the intensity of p53 expression. The lack of biological functionality of p53 with molecular abnormalities seemed to relate to fast growing LC whereas p53 expression detected by Western seemed more related to the wild type of p53.
López-Guerrero
J A
JA
Department of Clinical Biochemistry, Hospital Universitario La Fe, Valencia, Spain.
Bolufer-Gilabert
P
P
Marugán de la Concha
I
I
Barragán-González
E
E
Vera-Sempere
F J
FJ
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational
D066246:ErbB Receptors