Study: 'Optical biomarkers' may have utility in RCC

Madison, WI-A novel optical imaging technology is showing promise as a potential diagnostic tool for renal cell carcinoma (RCC).

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Second-harmonic generation (SHG) images are obtained with multiphoton microscopy of biopsy tissue from renal tumors, and analyses of these “optical biomarkers” using new digital technology and software reveals extracellular matrix-based differences between benign and malignant tissue as well as between tumor grades, reported first author Sara L. Best, MD, at the 2014 World Congress of Endourology and SWL in Taipei, Taiwan.

Dr. Best“Benign and malignant renal tumors can be differentiated using standard histopathology evaluation, but those techniques lack accuracy for determining Fuhrman grade when assessing small tissue samples such as those obtained from a tumor biopsy. In contrast to Fuhrman grading that is largely based on nuclear features, SHG signals are collagen based and have been shown to have prognostic value for predicting survival in patients with other malignancies, including breast and ovarian cancer,” said Dr. Best, assistant professor of urology at the University of Wisconsin School of Medicine and Public Health, Madison.

“These initial findings from SHG imaging of renal tissue are encouraging and support further investigation to determine if this technique can provide useful information for predicting the aggressiveness of renal cell carcinoma.”

The SHG image analysis is performed using Curvelet transform-based software, which was developed by researchers at the University of Wisconsin’s Laboratory for Optical and Computational Instrumentation. The software automatically extracts collagen fibers in the image, quantifies how well the fibers are aligned with respect to each other, and quantifies the information, converting it to a numerical value known as the alignment coefficient.

Capture of SHG images from the renal tissue samples was done using five-micron sections cut from tissue microarrays that were constructed from 0.6-mm biopsy cores of benign renal tissue and grades 1 to 4 RCC.

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“It is exciting that SHG signal was generated from small tissue samples that are similar in diameter to those obtained in renal tumor biopsy. SHG imaging also has other features that make it attractive as a diagnostic tool. It does not destroy the sample, and it is a flexible platform that can be used to study fresh tissue, stained tissue fixed on pathology slides, and even living cells in culture,” said Dr. Best.

Findings from the different specimens evaluated in the study showed significantly greater linear alignment of the collagen fibers comparing the high-grade RCC samples to both low-grade RCC and benign tissue.

“This finding is consistent with what has been reported using SHG to analyze other types of cancer, where aligned collagen fibers have been found to serve as a ‘scaffold’ for cancer cell migration,” Dr. Best said.

Corroboration that the optical biomarkers generated by SHG imaging are collagen based was the fact that standard histologic staining showed absence of collagen in tissue specimens generating very low signal.

Currently, the authors are planning studies to determine whether the SHG biomarkers correlate to clinical outcomes in patients with RCC.

“Our hope is to establish clinical relevancy so that the biomarker information could be used together with other prognostic information to improve individualized management plans for patients with renal tumors,” Dr. Best said.

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