The role of non-classical and chain-related human leukocyte antigen polymorphisms in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chain-related MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chain-related MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC. MATERIALS AND METHODS: In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 63 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx). Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2. RESULTS: The HLA disease association tests revealed a statistically significant predisposing association of HLA-F*01:01:02 (Pc = 0.0103, OR = 24.0194) with LSCC, while HLA-F*01:01:01 (Pc = 8.21e-04, OR = 0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically significant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P = 0.0054, haplotype score=-2.7801). CONCLUSION: Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of LSCC.

Mixed Eccrine Cutaneous Tumor with Folliculo-Sebaceous Differentiation: Case Report and Literature Review.

Background/Introduction: Cutaneous mixed tumor is a rare benign neoplasm that exhibits a wide range of metaplastic changes and differentiation in the epithelial, myoepithelial, and stromal components, which is often confused with various other skin lesions. Case report: We present an unusual case of a 58-year-old woman with a mixed tumor of the upper lip, previously misdiagnosed as adnexal carcinoma on a preoperative biopsy. The excision biopsy shows a well-circumscribed lesion composed of various cells and structures featuring folliculo-sebaceous differentiation embedded in a prominent chondromyxoid stroma. The immunohistochemical study proves the various lineages of differentiation and classifies the neoplasm as the less common eccrine subtype of cutaneous mixed tumor. Discussion: The common embryologic origin of the folliculo-sebaceous apocrine complex leads to a great histological variety of cellular components of mixed tumors and the formation of structures that resemble established types of adnexal neoplasms, which could be a diagnostic pitfall, especially on a small incision biopsy.

Associations of high-resolution-typing-defined MICA and MICB polymorphisms, and the levels of soluble MICA and MICB with Oral Squamous Cell Carcinoma in Bulgarian patients.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) is a malignancy characterized by an aggressive tumor growth and significant mortality. Clarifying mechanisms responsible for immunomodulation are among the main challenges for the development of personalized approaches for the management of patients with Oral Squamous Cell Carcinoma. The aim of the present study was to analyze the relevance of MICA and MICB to Oral Squamous Cell Carcinoma pathogenesis focusing on allele polymorphisms and the levels of soluble MICA and MICB molecules. MATERIALS AND METHODS: 73 patients diagnosed with Oral Squamous Cell Carcinoma and 149 healthy controls from the Bulgarian population were included in the study. MICA and MICB polymorphism was analyzed at high-resolution level using Next-Generation Sequencing. Serum levels of soluble MICA and MICB molecules were measured by ELISA. RESULTS: Our results show significant protective association with MICB*002:01, while relatively rare alleles MICB*018, *019, and *020 were observed with statistically significant increased frequency in Oral Squamous Cell Carcinoma patients compared to controls. Additionally, a predisposing association was observed for MICA*008:01-MICB*019 haplotype. A correlation analysis between functionally relevant MICA polymorphisms and sMICA showed that homozygosity for MICA-A5.1 or 129Val in OSCC patients was associated with significantly higher serum levels of sMICA. CONCLUSION: This is the first study showing significant associations between MICB alleles and Oral Squamous Cell Carcinoma and suggesting the possible role of MICB in immunosurveillance in Oral Squamous Cell Carcinoma development. Observed correlations between the levels of soluble MICA molecules and functionally relevant polymorphisms might represent a further step toward a better understanding of molecular mechanisms of Oral Squamous Cell Carcinoma and developing strategies for therapeutic targeting harnessing effective immunosurveillance.

VEGF expression, microvessel density and dendritic cell decrease in thyroid cancer.

Thyroid cancer is one of the five most common cancers in the age between 20 and 50 years. Many factors including the potent angiogenic vascular endothelial growth factor (VEGF) and different dendritic cell types are known to be related to thyroid tumourogenesis. The study was performed to address the expression of VEGF and microvessel density in thyroid cancers and to evaluate the effect of VEGF expression in thyroid tumour cells on the dendritic cells. We investigated 65 patients with different types of thyroid carcinomas: papillary (PTC), oncocytic (OTC), follicular (FTC) and anaplastic (ATC), immunohistochemically with antibodies against VEGF, CD1a, CD83, S100 and CD31. Our results suggest that the expression of VEGF is significantly more often in PTC than ATC (92.3% vs. 60.0%, p = 0.025). The microvessel density marked with CD31 in the tumour border of PTC was significantly higher as compared to FTC (p = 0.039), but not to ATC and OTC (p = 0.337 and 0.134). We found that CD1a- and CD83-positive cells were dispersed with variable density and in OC CD31+ vessel numbers were positively correlated with CD83+ dendritic cells in tumour stroma (R = 0.847, p = 0.016). We did not find statistically significant associations of the survival of patients with PTC after the surgical therapy with VEGF expression and MVD. In conclusion we may state that VEGF expression in tumour cells of thyroid cancer can induce neovascularization and suppress dendritic cells.