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

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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.

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Authors and Affiliations

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

    Byung Wook Choi & Sungmin Kang

  2. Department of Surgery, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea

    Young Ju Jeong & Sung Hwan Park

  3. Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea

    Hoon Kyu Oh

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Correspondence to Sungmin Kang.

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Conflict of Interest

Byung Wook Choi, Young Ju Jeong, Sung Hwan Park, Hoon Kyu Oh, and Sungmin Kang declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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The institutional review board of our institute approved this retrospective study, and the requirement to obtain informed consent was waived.

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Choi, B.W., Jeong, Y.J., Park, S.H. et al. Reverse Warburg Effect-Related Mitochondrial Activity and 18F-FDG Uptake in Invasive Ductal Carcinoma. Nucl Med Mol Imaging 53, 396–405 (2019). https://doi.org/10.1007/s13139-019-00613-x

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  • DOI: https://doi.org/10.1007/s13139-019-00613-x

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