Cytochrome c1 as a favorable prognostic marker in estrogen receptor-positive breast carcinoma
Ai Sato1, Kiyoshi Takagi1, Yasuhiro Miki2,3, Ayano Yoshimura1, Mizuki Hara1, Takanori Ishida4, Hironobu Sasano2,5 and Takashi Suzuki1
Departments of 1Pathology and Histotechnology, 2Anatomic Pathology and 4Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 3Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science, Tohoku University and 5Department of Pathology, Tohoku University Hospital, Sendai, Japan
Offprint requests to: Takashi Suzuki, MD, PhD., Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine. 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken, 980-8575 Japan. e-mail: t-suzuki@patholo2.med.tohoku.ac.jp
Summary. Background. Cytochrome c1 (CYC1) is a heme-containing subunit of mitochondria complex III and is mainly involved in cellular energy production. A recent study has demonstrated that CYC1 was overexpressed in breast carcinoma tissues and induced proliferation, migration and invasion of estrogen receptor (ER)-negative breast carcinoma cells. However, the clinical significance of CYC1 protein remains largely unclear in invasive breast carcinoma, and biological functions of CYC1 have not been reported in ER-positive breast carcinoma cells.
Materials and methods. We immunolocalized CYC1 in 172 invasive breast carcinomas and evaluated its clinical significance according to the ER-status. Subsequently, we examined the effects of CYC1 on proliferation, glycolysis and chemosensitivity to paclitaxel, which is one of the most common chemotherapeutic agents in breast cancer, in ER-positive breast carcinoma cells (MCF7 and T47D).
Results. CYC1 immunoreactivity was detected in 47% of ER-positive cases and 30% of ER-negative cases. Immunohistochemical CYC1 status was inversely associated with Ki67 in ER-positive cases, and it was a significantly favorable prognostic factor for both disease-free and breast cancer-specific survival of the patients. On the other hand, no significant association was detected between CYC1 status and clinico-pathological factors in ER-negative cases. In in vitro experiments, MCF7 and T47D cells transfected specific siRNA for CYC1 significantly increased cell proliferation activity, L-lactate production and cell viability after paclitaxel treatment.
Conclusion. These results suggest that CYC1 inhibits cell proliferation, glycolytic activity and increases chemosensitivity to paclitaxel in ER-positive breast carcinoma cells and that CYC1 status is a potent favorable prognostic factor in ER-positive breast cancer patients. Histol Histopathol 34, 1365-1375 (2019)
Key words: Breast Neoplasms, Chemosensitivity, Cytochrome c1, Estrogen Receptor, Prognosis
DOI: 10.14670/HH-18-130