Fox Chase Researcher Finds Genetic Differences in Rare Kidney Cancer Subtype That Could Lead to More Effective Treatment

Dr. Wei
Shuanzeng “Sam” Wei, MD, PhD, led a study which found that TFE3-rearranged renal cell carcinoma is a rare subtype of kidney cancer that can be misdiagnosed that was published in Modern Pathology.

PHILADELPHIA (February 22, 2024) — TFE3-rearranged renal cell carcinoma (rRCC) is a rare subtype of kidney cancer that can be misdiagnosed. This can affect treatment decisions and lead to patients receiving the wrong type of treatment. Now, a recently published study by scientists at Fox Chase Cancer Center identifies key genetic markers that can be used to distinguish rRCC from other cancers and also confirms which therapies are likely to be most effective. 

The findings are an important step towards more accurately diagnosing rRCC so that patients can receive the correct treatment for their cancer subtype, said corresponding author Shuanzeng “Sam” Wei, MD, PhD, an Associate Professor in the Department of Pathology at Fox Chase.

“If you can’t get correct diagnosis of this tumor, you cannot treat the patient correctly. I believe this will really affect patient management,” added Wei, who is also Medical Director of the Clinical Genomics Laboratory at Fox Chase.

Previous studies have provided clues that rRCC tumors are likely to be PD-L1 positive compared to other kidney cancer subtypes, suggesting that immune checkpoint inhibitors targeting this pathway could be an effective treatment.

However, rRCC is often misdiagnosed as two morphologically similar cancer subtypes: clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Figuring out how to correctly tell the difference is key to making sure patients receive the appropriate therapy for their type of cancer, Wei said.

For the new study, researchers from Fox Chase and several other institutions looked at a private database of tumor samples that had undergone molecular profiling over a 16-year period. This allowed them to analyze data from 20 patients with rRCC, a relatively large group, given the rarity of the disease. They compared this data set with 20 cases of pRCC and 392 cases of ccRCC.

They confirmed that PD-L1 positivity is indeed more likely in rRCC and found other genetic differences that could be used to make an accurate diagnosis. “We found 50% of TFE3-rearranged tumors — rRCC — were PD-L1 positive,” Wei said. “In contrast, papillary was only 19% and clear cell only 12%.” The findings, he added, show that immune checkpoint inhibitors should play an important role in the management of rRCC tumors.

Researchers also identified eight unique fusion genes in the rRCC tumors, one which has never been seen before. These could also be used to positively identify the subtype, he said.

The study, “Molecular Characterization of TFE3-Rearranged Renal Cell Carcinoma: A Comparative Study With Papillary and Clear Cell Renal Cell Carcinomas,” was published in Modern Pathology, the official journal of the United States and Canadian Academy of Pathology.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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