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<p>Although several ancillary tests are available in limited laboratories, diagnosis of microphthalmia (MiT)/TFE family translocation renal cell carcinoma (tRCC) could be challenging due to diverse and overlapping tumor morphology and the lack of reliable biomarkers. GPNMB has been recently identified as a diagnostic marker for various renal neoplasms with <i>FLCN/TSC/mTOR-TFE</i> alterations. However, the sensitivity and specificity of GPNMB immunostain are suboptimal and the result interpretation in ambiguous cases could be difficult. To search additional biomarkers that could improve the screening sensitivity and predict genetic aberrations in <i>FLCN/TSC/mTOR-TFE</i> pathway in renal tumors, we performed bioinformatic analysis of publicly available cancer databases and found GPR143, a transmembrane protein regulated by MiT transcription factors, was highly expressed in a subset of renal cell carcinomas (RCCs). In two kidney cancer cohorts of the Cancer Genome Atlas (TCGA), RCCs with high levels of <i>GPR143</i> expression were enriched for renal neoplasms with <i>FLCN/TSC/mTOR-TFE</i> alterations. Similar to GPNMB labeling, GPR143 immunostain was positive in the majority of tRCC cases and renal tumors with <i>FLCN/TSC/mTOR</i> alterations, suggesting that GPR143 could function as another surrogate marker for <i>FLCN</i>/<i>TSC/mTOR-TFE</i> alterations in certain renal tumors. Interestingly, despite the concordant GPR143 and GPNMB immunoreactivity in most renal neoplasms with <i>FLCN/TSC/mTOR-TFE</i> alterations, diffuse GPR143 immunostain was observed in some cases with negative or focal GPNMB labeling. Taken together, our results indicate GPR143 could serve as a useful adjunct marker to improve the sensitivity for screening renal tumors with <i>FLCN/TSC/mTOR-TFE</i> alterations.</p>

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GPR143, a novel immunohistochemical marker for renal tumors with FLCN/TSC/MTOR-TFE alterations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Qinyuan Li,
  • Anupama Singh,
  • Rong Hu,
  • Wei Huang,
  • Daniel D. Shapiro,
  • E. Jason Abel,
  • Yang Zong

摘要

Although several ancillary tests are available in limited laboratories, diagnosis of microphthalmia (MiT)/TFE family translocation renal cell carcinoma (tRCC) could be challenging due to diverse and overlapping tumor morphology and the lack of reliable biomarkers. GPNMB has been recently identified as a diagnostic marker for various renal neoplasms with FLCN/TSC/mTOR-TFE alterations. However, the sensitivity and specificity of GPNMB immunostain are suboptimal and the result interpretation in ambiguous cases could be difficult. To search additional biomarkers that could improve the screening sensitivity and predict genetic aberrations in FLCN/TSC/mTOR-TFE pathway in renal tumors, we performed bioinformatic analysis of publicly available cancer databases and found GPR143, a transmembrane protein regulated by MiT transcription factors, was highly expressed in a subset of renal cell carcinomas (RCCs). In two kidney cancer cohorts of the Cancer Genome Atlas (TCGA), RCCs with high levels of GPR143 expression were enriched for renal neoplasms with FLCN/TSC/mTOR-TFE alterations. Similar to GPNMB labeling, GPR143 immunostain was positive in the majority of tRCC cases and renal tumors with FLCN/TSC/mTOR alterations, suggesting that GPR143 could function as another surrogate marker for FLCN/TSC/mTOR-TFE alterations in certain renal tumors. Interestingly, despite the concordant GPR143 and GPNMB immunoreactivity in most renal neoplasms with FLCN/TSC/mTOR-TFE alterations, diffuse GPR143 immunostain was observed in some cases with negative or focal GPNMB labeling. Taken together, our results indicate GPR143 could serve as a useful adjunct marker to improve the sensitivity for screening renal tumors with FLCN/TSC/mTOR-TFE alterations.