Background <p>Medulloblastoma (MB) is the most common malignant brain tumor in children. Although the 5-year survival rate is approximately 70–80%, the current standard treatment results in severe and long-term side effects. The search for new anticancer immunotherapeutic targets has identified B7-H3 as a promising candidate in various solid tumors. However, the role of B7-H3 in MB remains unclear, and studies reporting its protein expression and association with clinicopathological characteristics are still limited.</p> Methods <p>In this study, B7-H3 protein expression was evaluated by immunohistochemistry in seven non-tumor samples and 43 molecularly characterized MB tissues. Its expression profile was correlated with B7-H3 (<i>CD276)</i> mRNA levels, which were previously determined by nCounter, as well as with the patients’ clinical features.</p> Results <p>Only 14.3% (1/7) of non-tumor brain and cerebellum tissues showed B7-H3 positivity, whereas 95.6% (41/43) of the MB samples expressed this protein at distinct levels. B7-H3 was found in the cytoplasm and on the membrane of cancer cells. A significant positive correlation was observed between <i>CD276</i> mRNA and B7-H3 protein levels. Moreover, high expression of B7-H3 protein was associated with worse overall survival and the presence of metastasis at diagnosis.</p> Conclusions <p>This is the first study to associate <i>CD276</i> mRNA and B7-H3 protein levels in MB, revealing a significant positive correlation. We observed that B7-H3 was overexpressed in MB compared to non-tumor brain tissue. High B7-H3 expression was associated with a worse outcome and with the presence of metastasis at diagnosis.</p>

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High B7-H3 protein expression in Medulloblastoma is associated with metastasis and unfavorable patient outcomes

  • Patrícia Fontão,
  • Gustavo Ramos Teixeira,
  • Daniel Antunes Moreno,
  • Rui Ferreira Marques,
  • João Norberto Stavale,
  • Suzana Maria Fleury Malheiros,
  • Carlos Almeida Júnior,
  • Bruna Minniti Mançano,
  • Rui Manuel Reis

摘要

Background

Medulloblastoma (MB) is the most common malignant brain tumor in children. Although the 5-year survival rate is approximately 70–80%, the current standard treatment results in severe and long-term side effects. The search for new anticancer immunotherapeutic targets has identified B7-H3 as a promising candidate in various solid tumors. However, the role of B7-H3 in MB remains unclear, and studies reporting its protein expression and association with clinicopathological characteristics are still limited.

Methods

In this study, B7-H3 protein expression was evaluated by immunohistochemistry in seven non-tumor samples and 43 molecularly characterized MB tissues. Its expression profile was correlated with B7-H3 (CD276) mRNA levels, which were previously determined by nCounter, as well as with the patients’ clinical features.

Results

Only 14.3% (1/7) of non-tumor brain and cerebellum tissues showed B7-H3 positivity, whereas 95.6% (41/43) of the MB samples expressed this protein at distinct levels. B7-H3 was found in the cytoplasm and on the membrane of cancer cells. A significant positive correlation was observed between CD276 mRNA and B7-H3 protein levels. Moreover, high expression of B7-H3 protein was associated with worse overall survival and the presence of metastasis at diagnosis.

Conclusions

This is the first study to associate CD276 mRNA and B7-H3 protein levels in MB, revealing a significant positive correlation. We observed that B7-H3 was overexpressed in MB compared to non-tumor brain tissue. High B7-H3 expression was associated with a worse outcome and with the presence of metastasis at diagnosis.