Clinical significance and biological role of claudin-1 in oral squamous cell carcinoma cells.

OBJECTIVES: Claudin (CLD), a major component of tight junctions, is a four-transmembrane protein, and 24 subtypes have been reported in humans. CLD expression is highly tissue-specific; CLD1 has been reported to be expressed in the skin and mucosa. There have been few reports on CLD1 expression and its function in oral cancer. MATERIALS AND METHODS: This retrospective study immunohistochemically evaluated CLD1 expression as prognostic predictors in 84 participants with oral squamous cell carcinoma (OSCC). Participants were classified as positive or negative based on staining intensity; the clinicopathologic characteristics and survival rates of the two groups were compared. To clarify the biological role of CLD1 in OSCC cells, we examined the effects of CLD1 overexpression on the invasion and proliferation of the OSCC cell line, SCCKN. RESULTS: We observed the immunohistochemical CLD1 expression in the cell membranes of OSCC cells. The disease-free survival rate was significantly lower in patients with CLD1-positive OSCC than in patients with CLD1-negative OSCC (P < .05). In vitro studies showed that cell proliferative capacity, motility, proteolytic activity, and invasive growth were promoted in CLD1-overexpressing SCCKN cells compared to those in control SCCKN cells. CONCLUSION: CLD1 may be a useful and potential prognostic factor for OSCC treatment.

Analysis of Oral and Gut Microbiome Composition and Its Impact in Patients with Oral Squamous Cell Carcinoma.

The impact of gut and oral microbiota on the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) is unknown. We compared the bacterial composition of dental plaque and feces between patients with OSCC and healthy controls (HCs). Fecal and dental plaque samples were collected from 7 HCs and 18 patients with OSCC before treatment initiation. Terminal restriction fragment-length polymorphism analysis of 16S rRNA genes was performed. Differences in bacterial diversity between the HC and OSCC groups were examined. We compared the occupancy of each bacterial species in samples taken from patients with OSCC and HCs and analyzed the correlation between PD-L1 expression in the tumor specimens and the occupancy of each bacterial species. The gut and oral microbiota of patients with OSCC were more varied than those of HCs. Porphyromonas and Prevotella were significantly more abundant in patients with OSCC than in HCs. The abundance of Clostridium subcluster XIVa in the gut microbiota of the PD-L1-positive group was significantly greater than that in the PD-L1-negative group. The oral and gut microbiomes of patients with OSCC were in a state of dysbiosis. Our results suggest the possibility of new cancer therapies targeting these disease-specific microbiomes using probiotics and synbiotics.

A Study of the Prognostic Factors for Late Cervical Lymph Node Metastasis and Distant Metastasis in Patients with cT1-2N0 Tongue Cancer.

Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor-stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and ≥3 tumor buds. In addition, the prognostic factors for distant metastasis included ≥4 lymph node metastases, ≥7 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers.

Clinical Efficacy and Safety of Lidocaine Tape for Topical Anesthesia of the Oral Mucosa: A Preliminary Controlled Trial.

Local anesthesia is administered to reduce pain-induced stress during dental treatment. However, local anesthetic injections are extremely painful; thus, methods to minimize this pain should be developed. Clinical studies on the pain-relieving effects of dental topical anesthetics have shown that few topical anesthetics provide fast and adequate pain relief without harming the oral mucosa. We examined the efficacy and safety of lidocaine tape, which has a potent topical anesthetic effect. Lidocaine tape was applied to the oral mucosa of 14 healthy participants, and its suppression effect was assessed by examining the pain intensity at the non-lidocaine tape-applied site using the visual analog evaluation scale and the verbal evaluation scale. Lidocaine tape application significantly reduced visual analog scale (VAS) scores during mucosal puncture compared to non-application (p < 0.01). Moreover, lidocaine tape application significantly reduced VAS scores during local anesthetic injection compared to non-application (p < 0.001). Adverse events were evaluated using the Common Terminology Criteria for Adverse Events, version 5.0. No adverse events attributed to the application of lidocaine tape were observed in any participant. The findings in this study suggest that the application of lidocaine tape before infiltration anesthesia can reduce patient distress.

Tumor-Infiltrating CD45RO+ Memory Cells Are Associated with Favorable Prognosis in Oral Squamous Cell Carcinoma Patients.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have been used to predict the prognosis of solid tumors. In this study, we investigated which molecules in TILs play a role in the prognosis of patients with oral squamous cell carcinoma (OSCC). METHODS: In a retrospective case-control study, we immunohistochemically evaluated the expression of CD3, CD8, CD45RO, Granzyme B, and the major histocompatibility complex class I chain-related molecule A (MICA) of the histocompatibility complex as predictors of prognosis in 33 patients with OSCC. The patients were classified as TILsHigh or TILsLow according to the number of TILs for each molecule in the central tumor (CT) and invasive margin (IM). Furthermore, MICA expression scores were determined based on the intensity of the staining. RESULTS: CD45RO+/TIL in the nonrecurrent group were significantly higher than those in the recurrent group in the CT and IM areas (p < 0.05). The disease-free survival/overall survival rate of the CD45RO+/TILsLow group in the CT and IM areas and the Granzyme B+/TILsLow group in the IM area was significantly lower than that of the CD45RO+/TILsHigh group and the Granzyme B+/TILsHigh group, respectively (p < 0.05). Furthermore, the MICA expression score of tumors around the CD45RO+/TILsHigh group was significantly higher than that of the CD45RO+/TILsLow group (p < 0.05). CONCLUSIONS: A high ratio of CD45RO-expressing TILs was associated with a disease-free/overall survival improvement in OSCC patients. Furthermore, the number of TILs that express CD45RO was associated with the expression of MICA in tumors. These results suggest that CD45RO-expressing TILs are useful biomarkers for OSCC.

Effects of Tongue Pressure on Cerebral Blood Volume Dynamics: A Functional Near-Infrared Spectroscopy Study.

Tongue pressure measurement (TPM) is an indicator of oral function. However, the association between tongue pressure and cerebral activation remains unclear. We used near-infrared spectroscopy (NIRS) to examine the correlation between cerebral cortex activation and tongue pressure stimulation against the anterior palatal mucosa. We measured voluntary maximum tongue pressure (MTP) using a TPM device; a pressure value of approximately 60% of the MTP was used for the experimental tongue pressure (MTP60%). We examined the effect of oral functional tongue pressure stimulation against the anterior palatal mucosa on cerebral activation using NIRS in 13 adults. Tongue pressure stimulation caused significant changes in cerebral blood flow in some areas compared with controls (p < 0.05). We performed a correlation analysis (p < 0.05) between MTP60% and changes in oxygenated hemoglobin in all 47 NIRS channels. MTP60% triggered activation of the right somatosensory motor area and right dorsolateral prefrontal cortex and deactivation of the anterior prefrontal cortex (APFC). TPM balloon-probe insertion in the oral cavity activated the bilateral somatosensory motor area and deactivated the wide area of the APFC. Moreover, MTP60% via the TPM balloon probe activated the bilateral somatosensory and motor cortex areas. Tongue pressure stimulation changes cerebral blood flow, and NIRS is useful in investigating the relationship between oral stimulation and brain function.

MICA A5.1 homozygous genotype is associated with a risk for early-onset oral cancer.

OBJECTIVES: Genetic predisposition is reportedly involved in early-onset oral cancer, although the genetic basis of this cancer remains unclear. The major histocompatibility complex class I-related chain A (MICA) plays a crucial role in eliminating malignant tumors by activating NKG2D, the natural killer (NK) receptor. MICA polymorphism might affect its binding to NKG2D. We aimed to find whether MICA gene microsatellite polymorphism is involved in the risk of oral squamous cell carcinoma (OSCC) development in a Japanese population. MATERIALS AND METHODS: We recruited 386 patients with OSCC and 103 healthy controls. Genomic DNA was analyzed by PCR for microsatellite repeat polymorphism in the transmembrane region of the MICA gene. The groups were compared for the prevalence of various alleles and their association with disease prognosis and survival. RESULTS: We found that adolescents and young adults (AYA) with OSCC were more likely to have the MICA A5.1 homozygous genotype than healthy controls (P = 0.0001), but their survival rate was higher than with other MICA genotypes (P = 0.0185). CONCLUSION: These results suggest that cancer's immune escape is facilitated by MICA's failure to activate the NK cells. MICA A5.1 homozygosity plays a role in individual susceptibility to OSCC, increasing the risk of early-onset oral cancer. However, such patients have a better prognosis than those with other MICA genotypes.

Development of Kikuchi-Fujimoto disease after a cervical lymph node metastasis of mucoepidermoid carcinoma: a case report.

Kikuchi-Fujimoto disease (KFD) was first reported by Kikuchi and Fujimoto in 1972 as a rare disease with lymphadenitis of unknown etiology. KFD is characterized by the main symptoms of fever and enlarged cervical lymph nodes (LNs), which are similar to the features of other LN-associated diseases. Therefore, it is difficult to diagnose this condition. We report the case of a 24-year-old woman who presented with KFD after surgery to treat a mucoepidermoid carcinoma of the palate and dissection of the left neck. The patient presented with a fever and right cervical lymphadenopathy when she visited our department for a regular follow-up related to the mucoepidermoid carcinoma. The results of computed tomography and ultrasonography evaluations led to a clinical diagnosis of lymph node metastasis, and a right neck dissection was performed. However, the pathological tissue analysis did not suggest malignancy but showed necrosis and various cellular infiltrates. We made a diagnosis of KFD from these clinical and pathological features. KFD may be misdiagnosed as a LN-associated disease such as metastasis. Clinically, KFD should be considered in patients with head and neck cancer who present with cervical lymphadenopathy.

Oral squamous cell carcinoma of the tongue dorsum with multiple cancer-associated mutations in the TP53 gene.

OBJECTIVES: Squamous cell carcinoma (SCC) of the tongue is one of the most common oral cancers, tongue dorsum being a site of low incidence of primary SCC. We report a rare case of SCC of the tongue dorsum in a 69-year-old man having a history of multiple cancers, including esophageal cancer, gastric cancer, and renal cell carcinoma. We discuss the findings in relation to past reports. MATERIALS AND METHODS: TP53 was PCR amplified using the genomic DNA extracted from peripheral blood mononuclear cells and formalin-fixed, paraffin-embedded tissue sections from the tumor site of the patient, and was sequenced. RESULTS: Physical examination revealed an elastic hard mass on the tongue dorsum, with a size of 22 × 15 mm. There were no palpable enlarged lymph nodes in the cervical and submandibular region. An incisional biopsy was performed. The diagnosis was well-differentiated SCC of tongue, T2N0M0, Stage II, and was treated through surgery. Surgical specimen of the deep ulcer area showed increased expression of p16 protein with no expression of p53 protein. He had a heterozygous gene polymorphism (c.215C > G: p.Pro72Arg) and a germline mutation (c.838A > T: p.Arg280*) of the TP53. However, there has been no recurrence or metastasis of the tongue carcinoma through the follow-up for 3 years. CONCLUSION: Germline TP53 mutation and codon 72 polymorphism are risk factors for uncontrolled cell proliferation, possibly leading to the patient's clinical phenotype. Therefore, strict follow-up is required when treating those who are at a higher risk of cancer due to a TP53 mutation.

Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up.

OBJECTIVES: Photodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up. MATERIALS AND METHODS: Thirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2mg/kg) intravenously 48h prior to light irradiation. Photoradiation was performed at doses of 100-150J/cm(2) using a 630-nm wavelength excimer dye laser. RESULTS: Six months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed. CONCLUSION: PDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.