Abstract
The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.
Highlights
Submitted: December 7, 2018 Accepted for publication: July 2, 2019 Last revision: August 1, 2019Lower lip squamous cell carcinoma (LLSCC) is one of the most frequent malignancies of the oral cavity and its development is associated with some risk factors, especially with chronic exposure to the sun’s ultraviolet radiation.[1]
The present study demonstrated for the first time a higher human leukocyte antigen-DR (HLA-DR) expression in lower lip squamous cell carcinoma (LLSCC) tumor cells when compared to cases of actinic cheilitis (AC), suggesting a potential
Even though a larger number of inflammatory cells was expected in LLSCC with higher epithelial expression of HLA-DR, the findings of this study reveal lack of significant difference in immunoreactivity to this protein regarding the intensity of the inflammatory infiltrate at the invasive front of these neoplasms
Summary
Submitted: December 7, 2018 Accepted for publication: July 2, 2019 Last revision: August 1, 2019Lower lip squamous cell carcinoma (LLSCC) is one of the most frequent malignancies of the oral cavity and its development is associated with some risk factors, especially with chronic exposure to the sun’s ultraviolet radiation.[1]. Studies have shown a strong association between the high expression of HLA-DR in malignant neoplastic cells and a favorable prognosis in patients with esophageal adenocarcinoma[4] and colorectal carcinoma.[7] investigations have suggested that HLA-DR expression by tumor cells stimulates the activation of CD4+ T helper 1 (Th1) lymphocytes and natural killer (NK) cells through presentation of tumor antigens. This process would trigger the production of Th1 cytokines, such as interferon gamma (IFN-γ), leading to larger genetic instability of tumor cells, activation of M1 macrophages and consequent destruction of neoplastic cells.[8,9] On the other hand, recent investigations have suggested that the expression of this molecule in neoplastic cells may be involved in protumoral activities.[10,11]
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