Clinicopathological characteristics of Japanese patients with breast cancer and MET exon 14 skipping alterations

Aims In non‐small cell lung cancer, alterations in mesenchymal‐epithelial transition ( MET ) have been recognized as novel therapeutic targets. In particular, the MET exon 14 skipping mutation ( METex14s ) is a rare oncogenic driver. Targeted therapy with MET tyrosine kinase inhibitors has recently been approved for this mutation. However, c‐MET expression and METex14s frequency and their clinicopathological effects in Japanese patients with breast cancer (BC) remain unknown. Methods Tissue microarray‐based immunohistochemistry (IHC) was performed to measure c‐MET expression in 930 patients with BC (808 with invasive and 122 with noninvasive BC). Reverse transcription polymerase chain reaction was performed to analyse METex14s in patients exhibiting c‐MET expression. Clinicopathological characteristics, including patient prognosis based on c‐MET expression and METex14s , were elucidated. Results IHC staining revealed c‐MET expression in 91/930 (9.7%) patients. Notably, IHC expression was frequently observed in apocrine carcinomas (11/26 cases). Among the c‐MET IHC‐positive cases, METex14s frequency was 25.9% (14/54 cases) in invasive BC and 54.1% (20/37 cases) in noninvasive BC. Furthermore, 4/11 informative noninvasive and invasive BC cases with apocrine differentiation carried METex14s . The nuclear grade was significantly higher in the METex14s‐ positive group among invasive BC with c‐met IHC expression. Furthermore, patients' age and negative rate for PgR IHC was significantly lower in the METex14s‐ positive group among noninvasive BC. Regarding the factors associated with patient outcomes, both c‐MET IHC staining and METex14s expression did not affect survival, regardless of the hormone receptor status. Conclusion High c‐MET expression and METex14s are common in apocrine carcinoma.