Redox Imaging of Human Breast Cancer Core Biopsies: A Preliminary Investigation

doi:10.1016/j.acra.2013.02.006

Academic Radiology

Volume 20, Issue 6, June 2013, Pages 764-768

https://doi.org/10.1016/j.acra.2013.02.006 Get rights and content

Rationale and Objectives

The clinical gold standard for breast cancer diagnosis relies on invasive biopsies followed by tissue fixation for subsequent histopathological examination. This process renders the specimens to be much less suitable for biochemical or metabolic analysis. Our previous metabolic imaging data in tumor xenograft models showed that the mitochondrial redox state is a sensitive indicator that can distinguish between normal and tumor tissue. In this study, we investigated whether the same redox imaging technique can be applied to core biopsy samples of human breast cancer and whether the mitochondrial redox state may serve as a novel metabolic biomarker that may be used to distinguish between normal and malignant breast tissue in the clinic. Our long-term objective was to identify novel metabolic imaging biomarkers for breast cancer diagnosis.

Materials and Methods

Both normal and cancerous tissue specimens were collected from the cancer-bearing breasts of three patients shortly after surgical resection. Core biopsies and tissue blocks were obtained from tumor and normal adjacent breast tissue, respectively. All specimens were snap-frozen with liquid nitrogen, embedded in chilled mounting medium with flavin adenine dinucleotide and reduced nicotinamide adenine dinucleotide reference standards adjacently placed, and scanned using the Chance redox scanner (ie, cryogenic nicotinamide adenine dinucleotide/oxidized flavoprotein fluorescence imager).

Results

Our preliminary data showed cancerous tissues had up to 10-fold higher oxidized flavoprotein signals and had elevated oxidized redox state compared to the normal tissues from the same patient. A high degree of tumor tissue heterogeneity in the redox indices was observed.

Conclusions

Our finding suggests that the identified redox imaging indices could differentiate between cancer and noncancer breast tissues without subjecting tissues to fixatives. We propose that this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples before tissue fixation.

Section snippets

Methods

Tissue collection from patients was performed according to a protocol approved by the internal review board of the University of Pennsylvania. Patient 1 was a 40-year-old woman with a 2.3-cm poorly differentiated, grade 3, and stage II invasive ductal carcinoma (IDC), with triple negative (TRN) status for estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2), negative nodes. Patient 2 was a 41-year-old woman with a poorly differentiated, grade 3, and stage

Results and discussion

The typical redox images of breast tumor tissue and normal breast tissue are displayed in Figure 1. The top two rows show the redox images of the tumor tissue from patient 1 at different locations. The bottom row contains the redox images of the normal tissue from the same patient. Tissue heterogeneity can be clearly seen in all of the images. We quantified the redox indices using the global averaging method and tabulated the results in Table 1. The first and most notable finding is the high

Conclusions

The mitochondrial redox states of human breast cancer tissue samples measured fluorometrically with the Chance redox scanner showed marked differences between the cancerous and normal tissues. The breast cancer tissue exhibited significantly higher signals of oxidized flavoproteins and more oxidized redox state than the normal tissues. The redox scanning results clearly indicated that the redox state in tumor tissues is heterogeneous. We propose that this novel redox scanning procedure may be

Acknowledgments

This article is dedicated to the memory of Dr. Britton Chance, who devoted himself to the research of this study with excitement and sleepless nights and his profound insights into science as well as his great attention to detail until the last moment of his life. This work was supported by Susan G. Komen Foundation grant KG081069 (L.Z.L.), National Institutes of Health (NIH) grant R01CA155348 (L.Z.L.), National Cancer Institute Cancer Center Support Grant 2-P30-CA-016520-35 (J.T.), Linda and

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Rapid CommunicationRedox Imaging of Human Breast Cancer Core Biopsies: A Preliminary Investigation

Rationale and Objectives

Materials and Methods

Results

Conclusions

Section snippets

Methods

Results and discussion

Conclusions

Acknowledgments

J Biol Chem

Anal Biochem

Biochim Biophys Acta

Respir Physiol

Int J Radiat Oncol Biol Physics

Mitochondrial redox imaging for cancer diagnostic and therapeutic studies

J Innov Optical Health Sci

Predicting melanoma metastatic potential by optical and magnetic resonance imaging

Adv Exp Med Biol

Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential

Proc Natl Acad Sci U S A

Quantitative mitochondrial redox imaging of breast cancer metastatic potential

J Biomed Optics

Rapid Communication
Redox Imaging of Human Breast Cancer Core Biopsies: A Preliminary Investigation