Reverse Warburg Effect-Related Mitochondrial Activity and 18F-FDG Uptake in Invasive Ductal Carcinoma

• Published in: Nuclear medicine and molecular imaging Vol. 53; no. 6; pp. 396 - 405
• Main Authors: Choi, Byung Wook, Jeong, Young Ju, Park, Sung Hwan, Oh, Hoon Kyu, Kang, Sungmin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2019; Springer Nature B.V; 대한핵의학회
• Subjects: Cancer; Cardiology; Correlation analysis; Cytochromes; Fluorine; Fluorine isotopes; Imaging; Medicine; Medicine & Public Health; Multivariate analysis; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Radiology; Statistical models; Tumors; 방사선과학; Cytochrome c oxidase; Reverse Warburg effect; Breast cancer; Invasive ductal carcinoma; Translocase of outer mitochondrial membrane 20; F-FDG
• ISSN: 1869-3474; 1869-3482
• DOI: 10.1007/s13139-019-00613-x

Purpose We evaluated the relationship between fluorine-18 fluoro-2-deoxy-glucose ( 18 F-FDG) uptake and mitochondrial activity in cancer cells and investigated the prognostic implications of this relationship in patients with invasive ductal carcinoma of the breast (IDCB). Methods One hundred forty-six patients with primary IDCB who underwent preoperative 18 F-FDG PET/CT followed by curative surgical resection were enrolled in the current study. Mitochondrial activity of cancer cells was assessed based on translocase of outer mitochondrial membrane 20 (TOMM20) expression and cytochrome C oxidase (COX) activity. A Pearson’s correlation analysis was used to assess the relationship between the maximum standardized uptake value of the primary tumour (pSUVmax) and mitochondrial activity. Clinicopathological factors, including pSUVmax, histological grade, oestrogen receptor (ER), progesterone receptor (PR), and TOMM20 expression; and COX activity, were assessed for the prediction of disease-free survival (DFS) using the Kaplan–Meier method and Cox proportional hazards model. Results Fourteen of the 146 subjects (9.6%) showed tumour recurrence. There was a significant positive correlation between 18 F-FDG uptake and the mitochondrial activity of cancer cells in patients with IDCB, and increased 18 F-FDG uptake and mitochondrial activity were significantly associated with a shorter DFS. Additionally, results from the receiver-operating curve analysis demonstrated that the cut-off values of pSUVmax, TOMM20 expression, and COX activity for the prediction of DFS were 7.76, 4, and 5, respectively. Further, results from the univariate analysis revealed that pSUVmax, TOMM20 expression, PR status, and histologic grade were significantly associated with DFS; however, the multivariate analysis revealed that only pSUVmax was associated with DFS (HR, 6.51; 95% CI, 1.91, 22.20; P  = 0.003). Conclusions The assessment of preoperative 18 F-FDG uptake and post-surgical mitochondrial activity may be used for the prediction of DFS in patients with IDCB.