Real-world data of EGFR mutation testing in Chinese non-small cell carcinoma: Low tumor cell number and tumor cellularity can be accepted.

INTRODUCTION: Molecular testing on advanced non-small cell lung cancer (NSCLC) often confront of limited specimen.The aim of the study is to compare the mutation frequency in adenocarcinoma samples with poor tumor cell content and the optimal samples, making the optimal strategy of mutation analysis.

METHODS: In this retrospective study, mutation status of EGFR, ALK, ROS1, BRAF, KRAS, RET, HER2, CMET, NRAS and PIK3CA in 1594 NSCLCs were tested by ARMS-PCR and qRT-PCR, consists of 790 cases of surgical specimens, 741 cases of small biopsies, 63 cases of cytology cell blocks. We analyzed the discrepancies in mutation frequency with optimal specimens and the suboptimal ones.

RESULTS: Comparing the gene mutation frequency in optimal and suboptimal samples, only the EGFR mutation rates of surgical samples (12.5 %, 1 out of 8) with < 10 % tumor cellularity was lower than in those with ≥ 10 % (57.1 %, 385 out of 674， p = 0.015). However, surgical specimens with low tumor cellularity (<20 %) were comparable to the qualified samples. The mutation frequency of EGFR in biopsy specimens with poor specimen adequacy( <20 %, <10 %, <5 %, <200, <100, <50) were comparable to the qualified samples. Low tumor cellularity (<20 %, <10 %, <5 %) and low tumor cell number (<200, <100, <50) was not associated with mutational rate for ALK, ROS1, BRAF, KRAS, RET, HER2, CMET, NRAS and PIK3CA mutations in small biopsy samples.

CONCLUSIONS: In clinical practice, specimen with low adequacy could attempt in gene mutation testing, including biopsy and surgical specimen. However, the amount of tumor for molecular testing should be reported and suboptimal samples with a negative EGFR mutation result should be considered for combination using of other mutation test method or repeat testing of an alternate tumor sample, especially for the surgical samples.