Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

Prognostic Value of CD45Ro+ T-Cell Expression in Patients With Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: The role of tumour-infiltrating CD45Ro+ T-cells in oral squamous cell carcinoma (OSCC) is unclear. This study aimed to evaluate prognostic biomarkers for OSCC. PATIENTS AND METHODS: We determined the density of tumour-infiltrating CD45Ro+ T cells in the parenchyma and stroma at the tumour centre (TCe) and invasive front (IF) and examined the association between the density of these cells and histopathological status in 142 patients. RESULTS: Five-year overall survival (OS) and recurrence-free survival were favourable in patients with high CD45Ro+ T-cell density in the TCe stroma. OS was favourable in patients with high CD45Ro+ T-cell density in the IF stroma. Stepwise Cox regression model analysis indicated that CD45Ro+ T-cells in the stroma of the IF and TCe were an independent prognostic factor for OS. CONCLUSION: CD45Ro+ T-cells in the stroma of the IF and TCe play a role in cancer immune surveillance and may be a useful prognostic factor.

Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma.

BACKGROUND: Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. METHODS: We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. RESULTS: Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front. CONCLUSIONS: The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4+ cells suppress the function of FoxP3+ T-cells and promote anti-tumor immunity in OSCC.

Borderline Microenvironment Fibrosis Is a Novel Poor Prognostic Marker of Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: The tumor microenvironment (TME) balances tumor growth and suppression through humoral factors and cell-cell interactions. In oral squamous cell carcinoma (OSCC), TMEs have been associated with prognosis of cancer patients and are evaluated by microscopy; however, these methods of evaluation vary among studies. MATERIALS AND METHODS: To evaluate the TME, borderline microenvironment fibrosis (bMF) was evaluated histologically in 236 OSCC cases and used to determine the clinicopathological status. RESULTS: bMF was observed in 47% (110 in 236 cases) of OSCC cases and associated with higher T category, N category, stage, histological grade and mode of invasion. bMF-positive was related to overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that bMF-positive was an independent factor for OS in all cases [n=226; HR=1.683 (1.018-2.781); p=0.042], especially in T1+T2 cases [n=186; HR=1.926 (1.079-3.440); p=0.024], and PFS in all cases [n=226; HR=2.254 (1.397-3.637); p=0.001]. CONCLUSION: bMF may act as a novel biomarker for OSCC.

Prognostic value of HLA class I expression in patients with oral squamous cell carcinoma.

Human leukocyte antigen (HLA) class Ⅰ molecules play a central role in anticancer immunity, but their prognostic value in oral squamous cell carcinoma (OSCC) remains unclear. We examined HLA class I expression in 2 distinct tumor compartments, namely, the tumor center and invasive front, and evaluated the association between its expression pattern and histopathological status in 137 cases with OSCC. Human leukocyte antigen class Ⅰ expression was graded semiquantitatively as high, low, and negative. At the invasive front of the tumor, HLA class I expression was high in 72 cases (52.6%), low in 44 cases (32.1%), and negative in 21 cases (15.3%). The HLA class I expression in the tumor center was high in 48 cases (35.0%), low in 58 cases (42.4%), and negative in 31 cases (22.6%). The 5-year overall survival and disease-specific survival rates were good in cases with high HLA class I expression at the invasive front; however, there was no significant difference in survival based on HLA class I expression in the tumor center. In addition, high HLA class I expression was correlated with high CD8+ T cell density, whereas negative HLA class I expression was correlated with low CD8+ T cell density at the invasive front. These results suggest that it is easier for CD8+ T cells to recognize presented peptides in the case of high HLA class Ⅰ expression at the tumor invasive front and could be a prognostic factor for OSCC.

Tumor-infiltrating CD8+ T-cell density is an independent prognostic marker for oral squamous cell carcinoma.

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved survival in head and neck squamous cell carcinoma. However, the prognostic value of TILs remains unclear in oral squamous cell carcinoma (OSCC). METHODS: We evaluated the associations between tumor-infiltrating CD8+ T-cell density and survival in five distinct compartments in 139 OSCC cases. RESULTS: There was a significant association between increased tumor-infiltrating CD8+ T cells and their distribution. High parenchymal CD8+ T-cell density at the invading tumor edge was associated with improved overall survival (OS) and disease-specific survival (DSS; P < 0.01 and P < 0.01, respectively). High stromal CD8+ T-cell density at the tumor periphery was also associated with improved recurrence-free survival (RFS; P < 0.01). Cox regression analysis revealed that high stromal CD8+ T-cell density at the tumor periphery and high parenchymal CD8+ T-cell density at the invading edge were independent prognostic makers (hazard ratio: 0.38 and 0.19, 95% confidence interval, 0.18-0.80 and 0.05-0.72, P = 0.01 and 0.01, respectively) for RFS and OS, respectively. CONCLUSIONS: Assessment of CD8+ T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis.

Diverticulum of the buccal mucosa: a rare case report and review of the literature.

BACKGROUND: Cases of diverticula of the buccal mucosa are extremely rare. Literature searches of databases such as PubMed/MEDLINE for this condition have revealed only 10 case reports. In this case report, we describe our experience in the management of this rare condition and review the previous 10 previously reported cases. CASE PRESENTATION: A 66-year-old man presented with a pouch containing inspissated food debris located posterior to the papilla of the parotid duct in his left buccal mucosa. The diagnosis of a diverticulum arising from the buccal mucosa was confirmed based on clinical and radiographic findings. Gross examination of the locally resected tissue specimen revealed a pouch measuring 14 mm in diameter and 8 mm in depth, that was whitish in color and had an elastic, soft, and smooth surface. Microscopic examination revealed a cyst-like lesion lined by stratified squamous epithelium and granulation tissue, with a chronic inflammatory infiltration in the peripheral stromal tissue of the epithelial layer. After surgical excision of the lesion, there was no recurrence during the follow-up period of 5 years and 10 months. CONCLUSIONS: We have presented a rare case of a diverticulum of the buccal mucosa. This is the first report of a case confirmed not only by the clinicopathological findings, but also by computed tomography and magnetic resonance imaging findings. From the magnetic resonance imaging and intraoperative findings, we inferred that the diverticulum was caused by an idiopathic developmental anomaly due to a partial defect of the buccinator muscle.