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Purpose <p>To investigate the prevalence of deficient DNA mismatch repair (dMMR) status in upper tract urothelial carcinoma (UTUC) and its association with clinicopathological characteristics as well as Nectin-4 immunohistochemical expression.</p> Methods <p>We retrospectively identified histologically confirmed UTUC cases treated at Peking University Third Hospital between December 2016 and September 2023. Eligible participants were required to also possess complete clinicopathological records and available formalin-fixed, paraffin-embedded (FFPE) tumor specimens suitable for immunohistochemical evaluation. MMR protein expression was categorized as either dMMR or proficient mismatch repair (pMMR), while Nectin-4 expression was quantitatively assessed using the H-score system. Samples were then classified as negative (H-score 0–14), low (H-score 15–99), medium (H-score 100–199), and high (H-score 200–300). Statistical significance was established at <i>P</i> &lt; 0.05 using two-tailed tests.</p> Results <p>A total of 339 patients were deemed eligible, with specimens successfully evaluated. 25 patients (7.4%) demonstrated dMMR status. High Nectin-4 expression was observed in 124 patients (36.7%). A statistically significant association was identified between dMMR status and elevated Nectin-4 expression (<i>P</i>&#xa0;= 0.044). No significant differences were detected between dMMR and pMMR groups regarding clinical parameters, including gender, age, tumor grade, or immunophenotypic characteristics.</p> Conclusion <p>Our study revealed that 7.4% of UTUC patients exhibited dMMR status, with heterogeneous Nectin-4 expression observed across the cohort. Notably, we demonstrated a statistically significant correlation between dMMR status and elevated Nectin-4 expression, suggesting potential biological interplay. The combined biomarker profile warrants further investigation as a predictive tool for therapeutic strategies involving antibody–drug conjugates (e.g., enfortumab vedotin) and immune checkpoint inhibitors.</p>

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Deficient DNA mismatch repair and Nectin-4 expression in upper tract urothelial carcinoma (UTUC)

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月7日

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  • Peichen Duan,
  • Le Yu,
  • Yichang Hao,
  • Shaohui Deng,
  • Peng Hong,
  • Min Lu,
  • Shudong Zhang

摘要

Purpose

To investigate the prevalence of deficient DNA mismatch repair (dMMR) status in upper tract urothelial carcinoma (UTUC) and its association with clinicopathological characteristics as well as Nectin-4 immunohistochemical expression.

Methods

We retrospectively identified histologically confirmed UTUC cases treated at Peking University Third Hospital between December 2016 and September 2023. Eligible participants were required to also possess complete clinicopathological records and available formalin-fixed, paraffin-embedded (FFPE) tumor specimens suitable for immunohistochemical evaluation. MMR protein expression was categorized as either dMMR or proficient mismatch repair (pMMR), while Nectin-4 expression was quantitatively assessed using the H-score system. Samples were then classified as negative (H-score 0–14), low (H-score 15–99), medium (H-score 100–199), and high (H-score 200–300). Statistical significance was established at P < 0.05 using two-tailed tests.

Results

A total of 339 patients were deemed eligible, with specimens successfully evaluated. 25 patients (7.4%) demonstrated dMMR status. High Nectin-4 expression was observed in 124 patients (36.7%). A statistically significant association was identified between dMMR status and elevated Nectin-4 expression (P = 0.044). No significant differences were detected between dMMR and pMMR groups regarding clinical parameters, including gender, age, tumor grade, or immunophenotypic characteristics.

Conclusion

Our study revealed that 7.4% of UTUC patients exhibited dMMR status, with heterogeneous Nectin-4 expression observed across the cohort. Notably, we demonstrated a statistically significant correlation between dMMR status and elevated Nectin-4 expression, suggesting potential biological interplay. The combined biomarker profile warrants further investigation as a predictive tool for therapeutic strategies involving antibody–drug conjugates (e.g., enfortumab vedotin) and immune checkpoint inhibitors.