Primary Oropharyngeal Squamous Cell Research Articles

Abstract A25: Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma

Abstract Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) represents a unique disease entity within head and neck cancer with rising incidence. Previous work has shown that alternative splicing events (ASEs) are prevalent in HPV+ OPSCC, but further validation is needed to understand the regulation of this process and its role in these tumors. In this study, eleven ASEs (GIT2, CTNNB1, MKNK2, MRPL33, SIPA1L3, SNHG6, SYCP2, TPRG1, ZHX2, ZNF331, and ELOVL1) were selected for validation from 109 previously published candidate ASEs to elucidate the post-transcriptional mechanisms of oncogenesis in HPV+ disease. In vitro qRT-PCR confirmed differential expression of 9 of 11 ASE candidates, and in silico analysis within the TCGA cohort confirmed 8 of 11 candidates. Six ASEs (MRPL33, SIPA1L3, SNHG6, TPRG1, ZHX2, and ELOVL1) showed significant differential expression across both methods. Further evaluation of chromatin structure revealed that ASEs strongly correlated with the cancer-specific distribution of acetylated lysine 27 of histone 3 (H3K27ac). Subsequent epigenetic treatment of HPV+ HNSCC cell lines (UM-SCC-047 and UPCI-SCC-090) with JQ1 not only induced downregulation of cancer-specific ASE isoforms but also growth inhibition in both cell lines. The UPCI-SCC-090 cell line, with greater ASE expression, also showed more significant growth inhibition after JQ1 treatment. This study confirms several novel cancer-specific ASEs in HPV+OPSCC and provides evidence for the role of chromatin structure in regulation of alternative splicing in HPV+OPSCC. Our findings highlight the role of epigenetic changes in the oncogenesis of HPV+OPSCC, which represents a unique, unexplored target for biomarkers, neoantigens, and therapeutics. Citation Format: Theresa Guo, Kristina D. A. Zambo, Fernando T. Zamuner, Tingting Ou, Christopher Hopkins, Dylan Z. Kelley, Hildegard A. Wulf, Ludmila V. Danilova, Michael Considine, David Sidransky, Alexander V. Favorov, Liliana Florea, Elana J. Fertig, Daria A. Gaykalova. Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A25.

Endoglin expression is associated with poor oncologic outcome in oral and oropharyngeal carcinoma

Conclusions. The present preliminary results suggest that endoglin (CD105)-assessed micro-vessel density (MVD) in primary oral and oropharyngeal squamous cell carcinomas (SCCs) may identify patients at risk of disease recurrence or poor oncological outcome after treatment. Objectives. MVD is an independent prognostic indicator in several human malignancies. Endoglin antibodies have shown a greater specificity for tumour vasculature in comparison with pan-endothelial markers. The present explorative study evaluated endoglin expression and its prognostic role in oral and oropharyngeal SCCs. Patients and methods. The study considered 13 consecutive cases of oral and oropharyngeal SCC with lymph node metastases (pN + ) and 13 consecutive pN0 cases. CD105-assessed MVD was calculated at 400× magnification. Results. The mean MVDs were 3.6 and 3.1 in pN+ and pN0 groups, respectively (p>0.05). The mean CD105-assessed MVDs were 4.7 in the group with locoregional recurrence and 2.9 in the group without locoregional recurrence or post-treatment diagnosis of distant metastasis (p=0.01). The mean CD105-assessed MVD in primary oral and oropharyngeal SCCs with poor oncological outcome (recurrence of disease or occurrence of distant metastasis) was 4.3. The mean MVD in primary oral and oropharyngeal SCCs with good outcome was 2.9. Statistical analysis showed a significant difference between CD105-assessed MVD in poor and good outcome groups (p=0.02).

Survivin expression is significantly higher in pN+ oral and oropharyngeal primary squamous cell carcinomas than in pN0 carcinomas

Conclusions. The preliminary results reported here suggest that survivin expression in primary oral and oropharyngeal squamous cell carcinomas (SCCs) may identify patients at risk of disease disseminating to neck lymph nodes. If these results are confirmed in larger series of patients it may imply that elective neck dissection should be considered in clinically N0 patients with oral and oropharyngeal SCCs who show high expression of survivin. Objective. To investigate the expression of survivin, a member of the inhibitor of apoptosis proteins family, in patients with primary oral and oropharyngeal SCCs with and without neck lymph node metastases. Material and methods. We considered 13 consecutive cases of oral and oropharyngeal SCCs with lymph node metastases (pN + ) and 13 cases of pN0 oral and oropharyngeal SCCs. The survivin reactivity of primary SCCs and lymph node metastases was evaluated immunohistochemically. A lesion was considered positive if >9.5% of the tumour cells showed diffuse strong staining. Results. Sporadic groups of normal basal and parabasal epithelial cells showed weak survivin staining. In SCCs, a nuclear reaction predominated. Eight primary pN+ SCCs were survivin-positive (mean expression 34.7%), compared to 5 primary pN0 SCCs (mean expression 12.3%; p=0.017). Statistical analysis disclosed significantly higher survivin expression in primary oral and oropharyngeal SCCs that developed distant non-lymphatic metastases (p=0.012).