Surgery for Cystadenoma of the Retromolar Pad Area With Reconstruction Using a Buccal Fat Pad Flap: A Case Report.

Salivary gland tumors can also occur rarely in the retromolar area, though common near the junction of hard and soft palate, labial mucosa, and buccal mucosa. Most salivary gland tumors in the retromolar pad area are malignant and should be excised. The cystadenoma is a rare, benign, salivary gland tumor. Importantly, incomplete resection of this tumor can lead to recurrence or cervical lymph node metastasis. We reported herein a case of cystadenoma arising in the right retromolar pad area in a 63-year-old male patient who underwent reconstruction using a buccal fat pad flap (BFPF) after the surgical removal of the tumor with a 10-mm margin left a defect with bone exposure. No evidence of recurrence or complication was found at the postoperative, three-year follow-up.

RIOK2 Contributes to Cell Growth and Protein Synthesis in Human Oral Squamous Cell Carcinoma.

Ribosomes are responsible for the protein synthesis that maintains cellular homeostasis and is required for the rapid cellular division of cancer cells. However, the role of ribosome biogenesis mediators in the malignant behavior of tongue squamous cell carcinoma (TSCC) is unknown. In this study, we found that the expression of RIOK2, a key enzyme involved in the maturation steps of the pre-40S ribosomal complex, was significantly associated with poorer overall survival in patients with TSCC. Further, multivariate analysis revealed that RIOK2 is an independent prognostic factor (hazard ratio, 3.53; 95% confidence interval, 1.19-10.91). Inhibition of RIOK2 expression by siRNA decreased cell growth and S6 ribosomal protein expression in oral squamous cell carcinoma cell lines. RIOK2 knockdown also led to a significant decrease in the protein synthesis in cancer cells. RIOK2 has potential application as a novel therapeutic target for TSCC treatment.

Possible Therapeutic Strategy Involving the Purine Synthesis Pathway Regulated by ITK in Tongue Squamous Cell Carcinoma.

The epidermal growth factor receptor is the only available tyrosine kinase molecular target for treating oral cancer. To improve the prognosis of tongue squamous cell carcinoma (TSCC) patients, a novel molecular target for tyrosine kinases is thus needed. We examined the expression of interleukin-2-inducible T-cell kinase (ITK) using immunohistochemistry, and the biological function of ITK was investigated using biochemical, phosphoproteomic, and metabolomic analyses. We found that ITK is overexpressed in TSCC patients with poor outcomes. The proliferation of oral cancer cell lines expressing ITK via transfection exhibited significant increases in three-dimensional culture assays and murine inoculation models with athymic male nude mice as compared with mock control cells. Suppressing the kinase activity using chemical inhibitors significantly reduced the increase in cell growth induced by ITK expression. Phosphoproteomic analyses revealed that ITK expression triggered phosphorylation of a novel tyrosine residue in trifunctional purine biosynthetic protein adenosine-3, an enzyme in the purine biosynthesis pathway. A significant increase in de novo biosynthesis of purines was observed in cells expressing ITK, which was abolished by the ITK inhibitor. ITK thus represents a potentially useful target for treating TSCC through modulation of purine biosynthesis.

Actinin-4 Expression Predicts Poor Disease-free Survival and Correlates with Delayed Lymph Node Metastasis in Patients with Completely Resected Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma is generally characterized by poor prognosis, and biomarkers are needed for development and selection of therapy. The purpose of this study was to assess expression of actinin-4, which has been implicated in cancer invasion and metastasis, to determine its viability as a prognostic indicator in oral squamous cell carcinoma. Clinical factors and tumor samples immunohistochemically stained for actinin-4 were retrospectively investigated in 55 patients who underwent curative surgery for oral squamous cell carcinoma. Overall survival and disease-free survival were estimated by Kaplan-Meier analysis. Significant differences were detected using the Pearson's chi-square and Fisher's exact tests. Univariate and multivariate analyses were performed with the Cox regression model. No association was found between expression of actinin-4 and clinical factors, including age or sex, or histopathological factors, including vascular invasion, lymphatic invasion, stage, mode of invasion, or histological atypicality. Expression of actinin-4 showed a positive correlation with delayed cervical lymph node metastasis. Disease-free survival was significantly lower in patients who were positive for expression of actinin-4 (p=0.010); overall survival showed no difference between patients with or without expression of actinin-4, however. The results revealed that actinin-4 was an independent prognostic factor for disease-free survival. Expression of actinin-4 showed a 73% sensitivity and 68% specificity for prediction of delayed cervical lymph node metastasis. In conclusion, actinin-4 may potentially be a useful biomarker for prediction of delayed cervical lymph node metastasis.

Actinin-4 protein overexpression as a predictive biomarker in adjuvant chemotherapy for resected lung adenocarcinoma.

AIM: Although several clinical trials demonstrated the benefits of platinum-combination adjuvant chemotherapy for stage II-IIIA lung adenocarcinoma, predictive biomarkers for the efficacy of such therapy have not yet been identified. We evaluated protein overexpression of actinin-4 as a predictive biomarker of the efficacy of adjuvant chemotherapy in resected lung adenocarcinoma. MATERIALS & METHODS: We measured actinin-4 protein levels in patients with completely resected stage II-IIIA lung adenocarcinoma using immunohistochemistry and then retrospectively compared survival between adjuvant chemotherapy and observation groups. RESULTS: A total of 148 eligible patients were classified into actinin-4 positive or negative cases by immunohistochemistry. In the former, patients with adjuvant chemotherapy survived significantly longer than those with observation (hazard ratio [HR]: 0.307; p = 0.028). But, no significant survival benefit was noted with adjuvant chemotherapy (HR: 0.926; p = 0.876) in the latter. CONCLUSION: This marker could predict the efficacy of adjuvant chemotherapy for resected lung adenocarcinoma patients.

A case of mucoepidermoid carcinoma with clear cell components occurring in retromolar region.

Mucoepidermoid carcinomas in the minor salivary glands usually originate in the palatine gland, and their occurrence in the retromolar region is rare. We report a rare case of mucoepidermoid carcinoma with clear cell components occurring in the retromolar region. The patient was a 63-year-old woman referred to our hospital with the chief complaint of a painless mass in the right retromolar region initially found during treatment at a local dental clinic. The 20×10-mm mass was well-defined, elastic, and flexible. The surface of the mucosa was healthy. The mass was clinically diagnosed as a gingival benign tumor in the right retromolar region. There were no significant findings in the patient's medical history. The tumor was resected under local anesthesia. Histopathology revealed that squamoid cells, undifferentiated intermediate cells, and clear cells were dominant, with mucus-producing cells in some areas. A mucoepidermoid carcinoma with clear cell components was diagnosed. There were no signs of recurrence or metastasis at 15 months postoperatively and the patient's progress has been satisfactory. Because the tumor was a painless, slow-growing mass, it was clinically diagnosed as a benign tumor of the gingiva, and resection was performed under local anesthesia without performing a biopsy. However, even if a mass in the retromolar region is clinically diagnosed as a benign tumor, the course of treatment should be decided after performing fine-needle aspiration cytology, taking into consideration the possibility of mucoepidermoid carcinoma.

Copy number increase of ACTN4 is a prognostic indicator in salivary gland carcinoma.

Copy number increase (CNI) of ACTN4 has been associated with poor prognosis and metastatic phenotypes in various human carcinomas. To identify a novel prognostic factor for salivary gland carcinoma, we investigated the copy number of ACTN4. We evaluated DNA copy number of ACTN4 in 58 patients with salivary gland carcinoma by using fluorescent in situ hybridization (FISH). CNI of ACTN4 was recognized in 14 of 58 patients (24.1%) with salivary gland carcinoma. The cases with CNI of ACTN4 were closely associated with histological grade (P = 0.047) and vascular invasion (P = 0.033). The patients with CNI of ACTN4 had a significantly worse prognosis than the patients with normal copy number of ACTN4 (P = 0.0005 log-rank test). Univariate analysis by the Cox proportional hazards model showed that histological grade, vascular invasion, and CNI of ACTN4 were independent risk factors for cancer death. Vascular invasion (hazard ratio [HR]: 7.46; 95% confidence interval [CI]: 1.98-28.06) and CNI of ACTN4 (HR: 3.23; 95% CI: 1.08-9.68) remained as risk factors for cancer death in multivariate analysis. Thus, CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma.

Soluble interleukin-6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy.

Preoperative chemoradiotherapy has been shown to improve the outcome of patients with esophageal cancer, but because response to this therapy varies, it is desirable to identify in advance individuals who would be unlikely to benefit, in order to avoid unnecessary adverse drug effects. The serum profiles of 84 cytokines and related proteins were determined in 37 patients with esophageal squamous cell carcinoma who received identical neoadjuvant preoperative chemoradiotherapy regimens and underwent surgical resection. Histological response to this therapy was assessed in surgically resected specimens. The serum soluble interleukin-6 receptor (sIL6R) level was significantly higher in 30 patients who failed to achieve a histological complete response (P = 0.005). Multivariate analysis revealed that the increased level of sIL6R was one of several significant independent predictors of an unfavorable outcome (hazard ratio, 2.87; P = 0.017). The increased level of this cytokine in patients who did not obtain a complete response was reproducibly observed in an independent cohort of 34 patients. Esophageal squamous cell carcinoma patients with an increased serum level of sIL6R are predicted to respond poorly to preoperative chemoradiotherapy, therefore, their exclusion from this treatment may be considered. Persistent systemic inflammation is implicated as a possible mechanism of resistance to this therapy.

SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis.

Salivary gland tumors are relatively rare and morphologically diverse and heterogeneous tumors; therefore, histogenesis-based tumor markers are sorely needed to aid in diagnosing and determining the cell type of origin. SRY-related HMG-box 10 (SOX10) protein is a transcription factor known to be crucial in the specification of the neural crest and maintenance of Schwann cells and melanocytes. In addition, positive expression has also been implicated in the major salivary gland. Here, we examined SOX10 expression in various salivary gland tumors to correlate this expression with myoepithelial markers. Overall, 76 malignant and 14 benign tumors were examined. SOX10 expression clearly delineated two distinct subtypes of human salivary gland tumors; acinic cell carcinomas, adenoid cystic carcinomas, epithelial-myoepithelial carcinomas, myoepithelial carcinomas, and pleomorphic adenomas, including the pleomorphic adenoma component of carcinoma, were SOX10 positive, while salivary duct carcinomas, mucoepidermoid carcinomas, an oncocytic carcinoma, Oncocytomas, and Warthin tumors were SOX10 negative. Also, SOX10 was expressed in solid-type or non-specific morphology salivary gland tumors, but was not expressed in poorly differentiated squamous cell carcinomas. In normal human salivary gland tissue, SOX10 expression was specific to the nuclei of acini and both luminal and abluminal cells of intercalated ducts but not in other sites. Moreover, the murine model suggested that SOX10 continued to be expressed from the developmental stage to adulthood in the acinar and both luminal and abluminal intercalated ducts in the major salivary gland. Thus, SOX10 is a novel marker for diagnosing and understanding the histogenesis of salivary gland tumors.