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Tumor-Associated Macrophage Correlated with Angiogenesis and Progression of Mucoepidermoid Carcinoma of Salivary Glands

  • Laboratory and Translational Research
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Abstract

Background

There is considerable controversy about whether tumor-associated macrophages (TAMs) promote or inhibit tumor progression. The present study examined the clinicopathologic significance of TAMs and their association with tumor angiogenesis, cell proliferation, and apoptosis in mucoepidermoid carcinoma (MEC). The potential effect of TAMs on cancer cells was also investigated.

Methods

CD68, CD34, Ki-67, and vascular endothelial growth factor (VEGF)-A immunohistochemical staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) were applied to samples from 41 MEC patients. The biologic effect of macrophages on MEC cancer cells was examined in a co-culture system.

Results

The proliferation index (PI) was 11.7 ± 5.9%, and the apoptotic index (AI) was 4.1 ± 2.3% in cancer patients. PI was significantly correlated with tumor grade, and the PI/AI ratio was significantly correlated with tumor size and stage. The distributions of intratumoral TAMs and microvessel density (MVD) were heterogeneous. TAM count associated strongly with tumor size, grading, and MEC staging. A greater intratumoral MVD was observed frequently in patients with large, intermediate/high-grade, and advanced-stage tumors. VEGF-A expression correlated significantly with tumor size and stage. MVD count was closely associated with TAM count and VEGF-A expression. Co-cultured cancer cells with macrophages increased migration and invasion ability of cancer cells. Co-cultured endothelial cells with cancer cells elevated VEGF-A expression, proliferation, and migration, and tube formation of endothelial cells.

Conclusion

Our data suggest that TAMs play a tumor-promoting role in MEC. The TAM count, intratumoral MVD, and PI/AI ratio are potentially useful markers of progression in patients with MEC.

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Acknowledgements

This work was supported by grants from the National Science Council NSC 96-2314-B-016-044, NHRI-EX97-9602BC, and Tri-Service General Hospital TSGH-C97-27, DOD97-20-05, and CMNDMC9705 Taiwan. The authors would like to Ms. Hsu-Hua Chu for her help in data analysis.

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Authors and Affiliations

  1. School of Dentistry, National Defense Medical Center, Taipei, Taiwan

    Yi-Shing Shieh DDS, PhD

  2. Department of Oral Diagnosis and Pathology, Tri-Service General Hospital, Taipei, Taiwan

    Yi-Shing Shieh DDS, PhD & Kuo-Chou Chou DDS

  3. Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan

    Yi-Jen Hung MD & Jin-Shuen Chen MD, PhD

  4. Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan

    Chung-Bao Hsieh MD

  5. Department of Oral and Maxillofacial Surgery, Chi Mei Medical Center, Tainan, Taiwan

    Shyun-Yeu Liu DDS

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  1. Yi-Shing Shieh DDS, PhD
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  2. Yi-Jen Hung MD
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  3. Chung-Bao Hsieh MD
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  4. Jin-Shuen Chen MD, PhD
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Correspondence to Yi-Shing Shieh DDS, PhD.

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Shieh, YS., Hung, YJ., Hsieh, CB. et al. Tumor-Associated Macrophage Correlated with Angiogenesis and Progression of Mucoepidermoid Carcinoma of Salivary Glands. Ann Surg Oncol 16, 751–760 (2009). https://doi.org/10.1245/s10434-008-0259-6

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