Clinicopathologic and Molecular Study of TFEB-altered Renal Cell Carcinomas

作者：Mengxin Zhang, Jie Xian, Jiaxiang Tang, Ying Yang, Jue Hu, Xiuyi Pan, Linmao Zheng, Yifan Kang, Mengni Zhang, Yu Xin, Xueqin Chen, Ling Nie, Hao Zeng, Qiao Zhou, Ni Chen · 发表于：The American Journal of Surgical Pathology · 年份：2025 · DOI：10.1097/pas.0000000000002458 · 被引用次数：7 · 研究领域：Renal cell carcinoma treatment、Renal and related cancers、Cancer Genomics and Diagnostics

TFEB -altered renal cell carcinoma (RCC) included TFEB -rearranged and TFEB -amplified RCC with unclear clinicopathological features and treatment options. Cases of TFEB -altered RCCs were collected. Fourteen cases showed TFEB rearrangement. Five MALAT1::TFEB fusions and one ACTB::TFEB fusion were verified. 8/14 TFEB -rearranged RCCs showed biphasic "pseudorosette" structure. All TFEB -rearranged RCC patients were alive without recurrence or metastasis after 3 to 122 months. Fifteen cases showed TFEB amplification, including 5 high-level amplifications (>10 copies) and ten low-level amplifications (5 to 10 copies), including 3 cases showing concomitant TFEB amplification and rearrangement. TFEB -amplified RCCs were high-grade, showing papillary, solid, nested, or alveolar arrangements of cells. In addition, 8 cases showed 3 to 4 TFEB signals were collected, indicating diverse morphologies. PDL1 membranous staining was observed in 9/10 TFEB -rearranged RCCs, and 11/13 TFEB -amplified RCCs. Copy number variation analysis revealed specific amplification of chromosome 6p21.1, where TFEB, VEGFA6 , and CCND3 were located, in one high- and 2 low-level amplification cases. Four cases with 3 to 4 TFEB signals did not show specific amplification of this region. Within the follow-up periods of 3 to 64 months, 8/13 TFEB -amplified RCC cases presented with metastasis, and 3/13 patients died in the 12th and 24th months. The treatment processes in several cases and the detailed therapeutic ...