Abstract

Abstract Background: One of the most interesting aspects relating to tumor heterogeneity is the relevance and clinical significance of mutant allele frequency (MAF) within a tumor. However, it remains unknown whether epidermal growth factor receptor (EGFR) MAF is associated with clinico-pathological features in patients. The aim of this study is to assess the clinico-pathological features associated with EGFR MAF in patients with non-small cell lung cancer. Methods: Based on a biobanking system in conjunction with our institution, we assessed EGFR substitution mutation status using the pyrosequencing method. Results: A total of 96 non-small cell lung cancer patients were identified as carrying EGFR substitution mutations using pyrosequencing to analyze histological and surgical specimens. In fifty-seven cases (59.4%) surgical specimens were taken and in 39 cases (40.6%) FFPE specimens were used. The median age of patients was 69 years (range: 37-84 years); stage IA/ IB/ IIA/ IIB/ IIIA/ IIIB/ IV, 32 (33.3%)/ 10 (10.4%)/ 7 (7.3%)/ 3 (3.1%)/ 5 (5.2%)/ 2 (2.1%)/ 37 (38.5%); mutation type L858R/ G719X/ L861Q, 85 (88.5%)/ 9 (9.4%)/ 2 (2.1%); histological type adenocarcinoma/ others, 90 (93.8%)/ 6 (6.2%); and median EGFR MAF was 18% (range: 6%-82%). The EGFR MAF did not differ significantly between 51 early stage (stage I, II) patients (53.1%, median: 19%) and 45 late stage (stage III, IV) patients (46.9%, median: 17%) (p = 0.48), 50 smoker patients (52.1%, median: 19%) and 46 never-smoker patients (47.9%, median: 16.5%) (p = 0.28), 58 non-elderly adults (≤ 70) patients (60.4%, median: 18.5%) and 38 elderly (> 70) patients (39.6%, median: 18%) (p = 0.37), and 47 male patients (49.0%, median: 19%) and 49 female patients (51.0%, median: 16.5%) (p = 0.13). However, the EGFR MAF was significantly elevated in 48 patients with moderately differentiated tumors (50.0%, median: 22%) compared to 30 patients with well differentiated tumors (31.3%, median: 13%) (p = 0.02) and 18 patients with poorly differentiated tumors (18.7%, median: 13%) (p = 0.01). Conclusion: EGFR MAF, measured by pyrosequencing, was not significantly associated with differences in clinical background, but was significantly associated with pathological differentiation in patients with non-small cell lung cancer. Citation Format: Akira Ono, Hirotsugu Kenmotsu, Masakuni Serizawa, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Tateaki Naito, Haruyasu Murakami, Yasuhisa Ohde, Masahiro Endo, Takashi Nakajima, Toshiaki Takahashi. Association of clinico-pathological features with epidermal growth factor receptor mutant allele frequency in patients with non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A61.

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