Clinical and genetic characteristics of early-stage multiple primary and independent primary lung adenocarcinoma patients

Aims: The difference between multiple primary lung cancers (MPLC) and intrapulmonary metastasis (IM) in patients with lung cancer is vital but controversial. Moreover, the genetic and clinical significance difference between MPLC and independent primary lung cancers (IPLC) patients is unknown.

Methods: This study retrospectively researched clinical and genetic data of MPLC and IPLC patients from January 2019 to May 2021 at the affiliated hospital of Qingdao University, China. Ninety-four tissue samples from 41 early-stage patients with MPLC, and 94 tissue samples from 94 early-stage patients with IPLC were performed to targeted sequencing.

Results: A total of 36 patients (88%) showed inconsistent driver mutations, and five MPLC patients (12%) shared single identical EGFR/BRAF/TP53 hotspot mutations in the early stage. In MPLC patients, high-frequency mutations included EGFR (63%), TP53 (12%), BRAF (12%), KRAS (10%), ERBB2 (4%), PIK3CA (3%), and MET (3%). In IPLC patients, high-frequency mutations included EGFR (55%), TP53(26%), KRAS (13%), MAP2K1 (5%), PIK3CA (4%), ERBB2 (4%), NF1 (4%), RET (3%), and BRAF (2%). The higher BRAF and fewer TP53 mutations may be related to the lower malignancy in MPLC patients.

Conclusions: The accuracy of pathological diagnosis in patients with early-stage MPLC does not need comprehensive molecular evaluation to supplement histology for differentiating early-stage MPLC and IM. Meanwhile, the molecular difference between MPLC and IPLC may be helpful to study the mechanism of MPLC pathogenesis.