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

Byung Wook Choi; Young Ju Jeong; Sung Hwan Park; Hoon Kyu Oh; Sungmin Kang

doi:10.1007/s13139-019-00613-x

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

Nucl Med Mol Imaging. 2019 Dec;53(6):396-405. doi: 10.1007/s13139-019-00613-x. Epub 2019 Oct 28.

Authors

Byung Wook Choi¹, Young Ju Jeong², Sung Hwan Park², Hoon Kyu Oh³, Sungmin Kang¹

Affiliations

¹ 1Department of Nuclear Medicine, Catholic University of Daegu School of Medicine, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu, 42472 Republic of Korea.
² 2Department of Surgery, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.
³ 3Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.

Abstract

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

Keywords: 18F-FDG; Breast cancer; Cytochrome c oxidase; Invasive ductal carcinoma; Reverse Warburg effect; Translocase of outer mitochondrial membrane 20.