Abstract
The aim of this study was to investigate succinate dehydrogenase (SDH) expression in breast cancer according to breast cancer molecular subtype using immunohistochemistry and to assess the clinical implications of SDH expression. Immunohistochemical staining for ER, PR, HER-2, Ki-67, HIF-1α, SDHA, and SDHB was performed on tissue microarrays of 721 breast cancers. According to the immunohistochemistry results for ER, PR, HER-2, and Ki-67 and fluorescence in situ hybridization (FISH) results for HER-2, breast cancer molecular subtypes were classified into luminal A, luminal B, HER-2, and triple-negative breast cancer (TNBC). HER-2 subtype breast cancers most frequently showed high-level expression of SDHA in tumor cells, while the luminal A subtype most frequently showed low or negative expression of SDHA in tumor cells (P = 0.032). Stromal SDHB expression rate was highest in HER-2 subtype and lowest in TNBC (P < 0.001). SDHA-negative breast cancers were associated with younger age at diagnosis (P = 0.012), and SDHB-negative breast cancers with lower histologic grade (P = 0.044) and lower Ki-67 labeling index (LI) (P = 0.046). Tumor phenotypes according to the SDH status were SDHA(+)/SDHB(+) > SDHA(-)/SDHB(-) > SDHA(-)/SDHB(+) > SDHA(+)/SDHB(-) in order of frequency. The stromal phenotypes were SDHA(-)/SDHB(-) > SDHA(+)/SDHB(+) > SDHA(-)/SDHB(+) > SDHA(+)/SDHB(-). In conclusion, loss of SDHA or SDHB expression was observed in about 3% of breast cancers in this study. Low SDH expression status in breast tumor cells was associated with younger age at diagnosis and low-grade histology.