Nucl Med Mol Imaging.  2019 Dec;53(6):396-405. 10.1007/s13139-019-00613-x.

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

• Choi BW
• Jeong YJ
• Park SH
• Oh HK
• Kang S

• KMID: 2469583
• DOI: http://doi.org/10.1007/s13139-019-00613-x

Abstract

PURPOSE
We evaluated the relationship between fluorine-18 fluoro-2-deoxy-glucose (¹â¸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 ¹â¸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 ¹â¸F-FDG uptake and the mitochondrial activity of cancer cells in patients with IDCB, and increased ¹â¸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 ¹â¸F-FDG uptake and post-surgical mitochondrial activity may be used for the prediction of DFS in patients with IDCB.

Keyword

¹⁸F-FDG; Breast cancer; Cytochrome c oxidase; Invasive ductal carcinoma; ReverseWarburg effect; Translocase of outer mitochondrial membrane 20

MeSH Terms

Breast
Breast Neoplasms
Carcinoma, Ductal*
Disease-Free Survival
Electron Transport Complex IV
Humans
Methods
Mitochondrial Membranes
Multivariate Analysis
Positron-Emission Tomography and Computed Tomography
Proportional Hazards Models
Receptors, Progesterone
Recurrence
Electron Transport Complex IV
Receptors, Progesterone