Background: p53 mutations are common in lung cancer, and have also been described in EGFR mutated
patients. The impact of p53 mutations in EGFR M+ patients is controversial, especially
if classified as “disruptive” and “non-disruptive” according to their functional effect
on the p53 protein as proposed by Poeta and colleagues. The aim of the study was therefore
to systematically analyze EGFR and p53 mutations within a cohort of patients with
lung cancer stage IV (UICC 7), to correlate alterations with clinical characteristics
and to investigate a potential impact of p53 mutations on treatment outcome.
Methods: 267 patients from a single center diagnosed with lung cancer stage IV were studied
for the presence of EGFR as well as inactivating p53 mutations. Methods for the detection
of EGFR mutations included Sanger Sequencing and hybridization based COBAS testing.
P53 mutations were detected by Sanger Sequencing. Clinical characteristics including
smoking status were available for all patients.
Results: 267 consecutive patients at the lung cancer center of the Pius-Hospital Oldenburg
were studied. The overall EGFR mutation rate was 19% (51/267) in all patients, 80%
(41/51) showing common mutations of exon 19 or 21. P53 disruptive mutation showed
in 16% (8/51) and p53 nondisruptive mutation occurred in 11% (22/51) whereas p53 WT
was found in 47% (24/51). In 8/51 (16%) patients p53 analysis was not successful.
OS was 37 months in p53 disruptive mutation and p53 WT patients compared to 19 months
in p53 nondisruptive mutation (p < 0,05). PFS on 1st line TKI therapy was 18 months
in p53 disruptive mutation and p53 WT patients and 6 months in p53 nondisruptive mutation
(p < 0,024). Similar results could be shown in the EGFR common but not in the uncommon
mutation subgroup.
Conclusion: Significant differences in PFS and OS in EGFR M+ patients were observed depending
on p53 mutation status. P53 mutational status is only predictive when disruptive and
non-disruptive P53 mutations are differentiated. P53 should be tested prospectively
in EGFR M+ patients as management on 1st line TKI may be different.
