TFE3-rearranged renal cell carcinoma has certain genetic markers that make it different from other types of kidney cancers, research found.
TFE3-rearranged renal cell carcinoma (rRCC), a rare subtype of kidney cancer, has been found to possess distinct genetic markers which distinguish it from similar kidney cancer subtypes clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) — findings which could potentially identify effective treatments and help avoid misdiagnoses, according to an expert.
“Since they are different tumors, I think the treatment should be different. And also, the diagnosis … sometimes it is difficult. Sometimes we need immunohistochemistry and molecular testing to confirm a diagnosis. And that’s the reason we have [released] this paper, we have clear-cut marker changes between the three tumors,” said Dr. Shuanzeng “Sam” Wei, an associate professor in the Department of Pathology and medical director of the Clinical Genomics Laboratory at Fox Chase Cancer Center in Philadelphia.
Wei and his colleagues, who published their findings in Modern Pathology, studied 20 patients with rRCC, 20 patients with pRCC and 392 patients with ccRCC, drawing on a database of tumor samples that underwent molecular profiling across a 16-year span, according to a news release from Fox Chase Cancer Center.
Researchers found patients with rRCC to be younger and more frequently female (median age 44.5 years, 75% female) than patients with pRCC (68.5 years, 25% female) and ccRCC (62 years, 27.8% female). They found eight unique fusion genes present in rRCC tumors, including one that was previously unidentified — distinguishing features that could be used to ensure proper diagnosis and potentially develop treatments.
“This tumor is very rare,” said Wei. “So far, the standardized treatment for this tumor has not been established. … Basically, this tumor was treated just with the therapy we [use when we] treat a patient with a clear cell renal cell carcinoma. But right now, we know from [the findings in] this paper the tumor is totally different from the molecular changes. … We need to develop more effective therapy for this tumor. But [for] the more effective therapy, we may need some time.”
However, Wei and his fellow researchers found 50% occurrence of PD-L1 positivity among patients with rRCC, versus 19% among patients with pRCC and 12.2% among patients with ccRCC.
PD-L1, as defined by the National Cancer Institute, is a protein that serves as a “brake” for the body’s immune system and is found in high levels on some cancer cells — and, in turn, can prevent the body’s immune system from dealing with cancer cells. Drugs known as immune checkpoint inhibitors counter this and enable the immune system to kill cancer cells. PD-L1 inhibitors cited by the American Cancer Society include Tecentriq (atezolizumab), Bavencio (avelumab) and Imfinzi (durvalumab).
“[We] found that about 50% of translocated renal cell carcinoma has a PD-L1 expression — that means possibly we can use checkpoint inhibitor therapy for this tumor [type],” Wei said.
There will be approximately 81,610 new cases of kidney cancer and 14,390 deaths from kidney cancer in the United States in 2024, according to the American Cancer Society, which said that approximately 90% of cases of kidney cancer are renal cell carcinoma. Renal cell carcinoma with a TFE3 rearrangement accounts for approximately 1% of adult cases of renal cell carcinoma, according to findings published in The American Journal of Surgical Pathology.
Proper diagnosis of rRCC, however, remains challenging, due to it being structurally similar to more common subtypes of kidney cancer, Wei explained.
“The translocation tumor has a morphology similar to clear cell and papillary renal cell carcinoma,” he said. “That’s why sometimes if you don’t do the molecular testing, if don’t do all the routine immunohistochemistry it’s really hard to get an accurate diagnosis.”
Proper diagnosis, he noted, can often require a team of experts.
“For any treatment, I think that the first thing [is that] the pathology diagnosis is very important. So, you can go to a cancer center such as the Fox Chase Cancer Center, you can have a very specialized team including the oncologist, urologist and pathologist look over the case, not only from pathology, they can also look at an imaging study, and also clinical features,” Wei said. “We always have a tumor board for the difficult cases. If you have a specialized group to treat the patient, the patient will get more appropriate treatment and management.”
If diagnosed, Wei urged all patients with this tumor type to undergo PDL1 immunohistochemistry testing, “because if it’s possible we can treat the patient with the immune check inhibitor.”
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