Immunohistochemical Expression of Tumour-Associated Macrophage Related Marker (CD68) and Proliferative Marker Ki-67 in Malignant Salivary Glands Tumour: Correlation with the Clinicopathological Factors, Oestrogen Receptor-α and HER-2

Abstract

Introduction: In the majority of malignant tumours including salivary glands tumours, the clinical stage and histological features are considered the most valuable prognostic and predictive factors for targeted therapy. Nevertheless, new prognostic factors for the Mucoepidermoid Carcinoma (MEC) are required due to the high rate of recurrence that occurs even with the early stage of the disease. The Adenoid Cystic Carcinoma (ACC) also needs more effective treatment as it show high rate of local recurrence and distant metastasis, even after surgical excision and radiotherapy. Aim: To assess the immunohistochemical expression of Tumour Associated Macrophage (TAMs) related marker (CD68) and proliferative marker (Ki-67) in salivary carcinomas (MEC and ACC). Furthermore, to study their correlation with clinicopathological factors, ERα, and HER-2 to detect the usefulness of these markers in the prognosis of such tumours. Materials and Methods: The present study was a crosssectional study conducted at Departments of Pathology, Surgery, Zagazig and Banha Universities, Egypt. The study included 37 salivary carcinomas (25 cases of MEC and 12 cases of ACC). The control group consisted of 10 normal salivary tissues. All paraffin blocks were dissected and stained with H&E to confirm the diagnosis and grade the tumours. IHC expression of CD68 and Ki-67 was assessed in all the cases and further correlated with clinicopathological factors, ERα and HER-2. Results: High TAMs was detected in 64.0% of MEC and 41.7% of ACC. High TAMs was significantly detected in high grades (p=0.006 and 0.045 for MEC and ACC respectively), in advanced stage (p=0.033 and 0.015 for MEC and ACC respectively), and in larger MEC (p=0.017). Ki-67 was significantly expressed in MEC compared to ACC (p=0.046), it was significantly expressed in high-grades MEC (p=0.011) and ACC (p=0.01). ERα was detected in 16.0% of MEC and 25.0% of ACC. HER-2 was detected in 12.0% of MEC and 16.7% of ACC. Correlation between CD68 and Ki-67 among the studied carcinomas revealed a significant moderate positive correlation (r=0.449, p=0.005). Conclusion: High level of TAMs expressed by CD68 and high proliferative activity measured by Ki-67 could be regarded as a poor prognostic parameter in MEC and ACC. A strong correlation between both markers was found, thus controlling the level of TAMs may have promoting role in targeted therapy. However, these results pointed towards a limited application of ERα and HER-2 in targeted therapy due to limited expressions in the present studied carcinomas.

Keywords

• adenoid cystic carcinoma
• mucoepidermoid carcinoma
• proliferative index
• steroid hormone receptors
• tumour microenvironment