October 31, 2019
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Emerging thyroid cancer test may prevent unnecessary surgeries

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Jialing Zhang, PhD 
Jialing Zhang
Rachel DeHoog 
Rachel DeHoog

Thyroid cancer is among the most curable types of cancer, with relative survival rates close to 100% for localized and regional tumors. Incidence of the malignancy has increased rapidly, with about 52,000 new cases diagnosed each year in the United States, according to American Cancer Society data.
Fine-needle aspiration, which is the current standard in thyroid cancer diagnostics, yields inconclusive results in about one of every five cases. In these cases, patients often undergo a follow-up genetic test, which is prone to false-positive results. This may prompt surgical intervention, which can lead to lifetime hormone replacement therapy and other repercussions and ultimately may prove unnecessary.
FNA [fine-needle aspiration] samples based on cytology is very challenging, and thyroid surgery may be required for the final diagnosis,” Jialing Zhang, PhD, research associate at The University of Texas at Austin, said in an interview with HemOnc Today. “However, in the majority of these surgical cases, the lesion is found to be benign on final histopathology, and the diagnostic surgery was therefore possibly unnecessary.”

Zhang, graduate student Rachel DeHoog and colleagues at The University of Texas at Austin and Baylor College of Medicine, have developed a preoperative thyroid cancer test that is not only faster, but approximately two-thirds more accurate than the current diagnostic tests. Zhang and DeHoog spoke with HemOnc Today about the potential for their test to prevent excessive false-positive results and surgeries.

Question: How did you decide to focus your research on a new test for thyroid cancer?

Zhang: Our team leader, Livia S. Eberlin, PhD, has been working in the mass spectrometry field for over 10 years. In 2015, she joined UT Austin in the chemistry department and started a collaboration with James W. Suliburk, MD, who specializes in the treatment of tumors of the thyroid, parathyroid and adrenal gland at Baylor College of Medicine. According to Dr. Suliburk, finding a way to quickly identify FNA samples would greatly benefit clinics. There is a critical need for new technologies for accurate, timely and comprehensive diagnosis of thyroid FNA biopsies.

Q: Why is FNA so often inconclusive?
DeHoog: Follicular thyroid cancer has cells that look the same as those of a benign thyroid tumor called a follicular adenoma. Because these cells look identical under a microscope, they are impossible to tell apart from an FNA smear alone, as the only difference between these two tumor types is that the follicular carcinoma cells invade the surrounding tissue and bloodstream. This morphologic feature is lost when looking at a smear of cells on a slide. These patients that receive an indeterminate FNA result often require surgery for a final diagnosis, which has additional risk and cost for the patient. However, in most these cases the tumor ends up being benign, and the surgery was not necessary.

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Q: What does the new test entail?

DeHoog: Our test looks at different molecules in the cells of the FNA biopsy samples in order to determine if a thyroid nodule is benign or malignant. This test entails using a technique called desorption electrospray ionization mass spectrometry to analyze the FNA smear directly, without any sample treatment or modification. With this technique, we can detect different lipids and metabolites in the FNA smears and use statistical models that we’ve built to predict if the tumor is benign or malignant. This will allow clinicians to more accurately determine if a patient has cancer and allow patients who ultimately receive a benign diagnosis to avoid an unnecessary surgery.

Q: How does the new test perform vs. the traditional cytology approach?

Zhang: FNA obtains cells from nodules. When examining these cells under a microscope, benign follicular thyroid adenoma and malignant follicular thyroid carcinoma have identical cytological behavior, which is impossible for the pathologist to differentiate. Our new test platform, which is a mass spectrometric system, uses molecular information instead of morphological information to differentiate the two most challenging tumor types.

Q: What is the next step for research?

DeHoog: Our next step is to perform a large, multicenter validation study and test the prediction of our statistical models on a large set of FNA samples. This will allow us to evaluate whether the test can be used to diagnose nodules from patients around the world.

Q: How might this influence clinical practice in the future?

Zhang: With ongoing study and more validation tests, we envision that the new test could serve as a routine analysis for indeterminate FNA samples acquired from clinics. The patients won’t have to wait for a couple of weeks to get the results and will have a clear diagnosis on the same day.

For more information:

Rachel J. DeHoog can be reached at Eberlin Research Group, 105 E. 24th St., Stop A5300, Austin, TX 78712; email: rdehoog@texas.edu.

Jialing Zhang, PhD, can be reached at Eberlin Research Group, 105 E. 24th St., Stop A5300, Austin, TX 78712; email: jialingzhang@utexas.edu.

References:

American Cancer Society. Thyroid cancer survival rates by type and stage. www.cancer.org/cancer/thyroid-cancer/detection-diagnosis-staging/survival-rates.html. Accessed Oct. 28, 2019.

DeHoog RJ, et al. Proc Natl Acad Sci U S A. 2019;doi:10.1073/pnas.1911333116.

Disclosures: DeHoog and Zhang report being inventors on a provisional patent relating to the use of mass spectrometry for diagnosis of thyroid cancer.