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Background <p>In metastatic colorectal cancer (mCRC), resistance to anti-EGFR monoclonal antibodies persists even in RAS/BRAF wild-type tumors. EGFR’s role in tumor angiogenesis may contribute to this resistance and deserves further exploration.</p> Objective <p>To assess EGFR protein expression and angiogenesis using immunohistochemistry (IHC) in mCRC, and to perform a molecular study of EGFR hotspot mutations.</p> Patients and methods <p>This retrospective study analyzed 61 FFPE metastatic colorectal cancer samples from Tunisian patients. EGFR protein expression and microvascular density were evaluated by IHC, and EGFR hotspot mutations were screened by PCR and Sanger sequencing.</p> Results <p>EGFR showed cytoplasmic expression in all cases. High expression (IHC score 3) was observed in 34.8% (16/46) of interpretable samples, while 50% (23/46) had low or no expression (score 0 or 1). MVD ranged from 8.66 to 85.33 (mean: 28.78). EGFR rs1050171 was identified in 31/40 patients (77.5%). EGFR abnormal expression was significantly associated with elevated MVD (<i>p</i> = 0.015), but not with EGFR mutation status. </p> Conclusion <p>The significant association between EGFR abnormal expression and increased microvascular density (MVD) in metastatic colorectal cancer highlights the intertwined role of proliferative and angiogenic pathways in tumor progression. These immunohistochemical and molecular findings reinforce the relevance of EGFR not only as a biomarker for targeted anti-EGFR therapies but also as a potential driver of tumor angiogenesis. This dual involvement suggests that combined therapeutic strategies targeting both EGFR signaling and angiogenesis could offer enhanced clinical benefit for patients with mCRC.</p>

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Immunohistochemical evaluation of EGFR protein expression and microvascular density reveals an angiogenic signature in Tunisian patients with metastatic colorectal cancer

  • 期刊论文

  • 发表日期：

    2025年12月28日

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  • Amira Jaballah Gabteni,
  • Ines Ben Ayed,
  • Hamza Yaiche,
  • Nadia Ben Jemii,
  • Dorra Wider,
  • Monia Ardhaoui,
  • Emna Fehri,
  • Afifa Maaloul,
  • Essia Habbechi,
  • Emna Ennaifer,
  • Haifa Tounsi

摘要

Background

In metastatic colorectal cancer (mCRC), resistance to anti-EGFR monoclonal antibodies persists even in RAS/BRAF wild-type tumors. EGFR’s role in tumor angiogenesis may contribute to this resistance and deserves further exploration.

Objective

To assess EGFR protein expression and angiogenesis using immunohistochemistry (IHC) in mCRC, and to perform a molecular study of EGFR hotspot mutations.

Patients and methods

This retrospective study analyzed 61 FFPE metastatic colorectal cancer samples from Tunisian patients. EGFR protein expression and microvascular density were evaluated by IHC, and EGFR hotspot mutations were screened by PCR and Sanger sequencing.

Results

EGFR showed cytoplasmic expression in all cases. High expression (IHC score 3) was observed in 34.8% (16/46) of interpretable samples, while 50% (23/46) had low or no expression (score 0 or 1). MVD ranged from 8.66 to 85.33 (mean: 28.78). EGFR rs1050171 was identified in 31/40 patients (77.5%). EGFR abnormal expression was significantly associated with elevated MVD (p = 0.015), but not with EGFR mutation status.

Conclusion

The significant association between EGFR abnormal expression and increased microvascular density (MVD) in metastatic colorectal cancer highlights the intertwined role of proliferative and angiogenic pathways in tumor progression. These immunohistochemical and molecular findings reinforce the relevance of EGFR not only as a biomarker for targeted anti-EGFR therapies but also as a potential driver of tumor angiogenesis. This dual involvement suggests that combined therapeutic strategies targeting both EGFR signaling and angiogenesis could offer enhanced clinical benefit for patients with mCRC.