Polarization and Distribution of Tumor-Associated Macrophages and COX-2 Expression in Basal Cell Carcinoma of the Ocular Adnexae

ABSTRACT

Purpose: Basal cell carcinoma (BCC) is a locally invasive skin tumor which can be subdivided into a circumscribed nodular and an invasive fibrosing subtype. There is increasing evidence that macrophages play an important role in interacting between tumor cells and their microenvironment, thereby affecting not only the invasive potential but also the patients’ prognosis. Thus, we wanted to compare these two BCC variants with regard to tumor-related inflammation, COX-2 expression, distribution, and polarization of tumor-associated macrophages.

Material and Methods: 30 BCCs (nodular: n = 15; fibrosing: n = 15) of the ocular adnexae were investigated by histopathology and immunohistochemistry. The grade of inflammation was evaluated on hematoxylin and eosin stains (score: 0–3). Immunohistochemical stains for CD68 (macrophages), Ki67 (proliferative activity), and COX-2 as well as immunofluorescence stains for CD68 and CD163 (to distinguish M1 and M2 macrophage subtypes) were performed. SPSS was used for statistical analysis.

Results: Fibrosing BCCs were predominantly located on the lower lid, while nodular BCCs showed a broader distribution (p = 0.013). The fibrosing BCC subtype was associated with a higher degree of inflammation (p < 0.001) and revealed a higher COX-2 immunoreactivity than nodular BCC (p = 0.012). COX-2-positive cells were predominantly located on the infiltrating edge of the tumor. Macrophage polarization was balanced regarding M1 and M2 macrophage subtypes. There was no difference in macrophage number (p = 0.389) or polarization (p = 0.161) between nodular and fibrosing BCC.

Conclusions: The findings indicate that COX-2 represents a factor for invasion of BCC. Macrophage polarization did not play a major role for aggressive behavior. However, other inflammatory components than tumor-associated macrophages seem to be involved in tissue destruction and thereby an invading growth pattern since fibrosing BCC revealed a significantly more intense inflammatory reaction in the surrounding tissue.

KEYWORDS:

• Basal cell carcinoma
• macrophages
• polarization
• COX-2
• ocular adnexae

Acknowledgments

The study was presented in part at the Annual Meeting of the Deutsche Ophthalmologische Gesellschaft (DOG-Congress 2015). This work was also submitted as part of a doctoral thesis at the University of Bonn.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary Material

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Additional information

Funding

None.