RELATIONSHIP OF P53 MOLECULAR ABNORMALITIES WITH FLOW-CYTOMETRY AND GROWTH-FACTOR RECEPTOR CONTENT IN LUNG-CANCER

This study attempts to clarify the oncological significance of the p53 molecular abnormalities and p53 expression in lung cancer (LC) and th eir relationship with flow cytometry (FC) parameters and epidermal gro wth factor receptor (EGFR). The study includes 65 samples taken from b oth LC and normal lung (NL). The p53 molecular abnormalities of exons 4-8 were studied by single strand conformation polymorphisms (SSCP) an d the loss of heterozygosity (LOH) of exon 4 by the Metzler method. P5 3 protein was detected by Western blot. EGFR was determined by a radio ligand assay using [I-125]EGF. The FC parameters S phase fraction (SPF ), DNA index (D.I.), G1G0 and growth rate (G2M + SPF) were evaluated f rom cellular monosuspensions. The LC with SSCP p53 molecular abnormali ties 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. Ne ither the relationship between the molecular results and p53 expressio n 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 fr action cells decrease significantly (P < 0.05) with the intensity of p 53 expression. The lack of biological functionality of p53 with molecu lar abnormalities seemed to relate to fast growing LC whereas p53 expr ession detected by Western seemed more related to the wild type of p53 . (C) 1998 Elsevier Science B.V.