Cyclin D1 and Ki-67 expression and its correlation with histopathological parameters and cervical lymph node metastasis in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor among oral cancers. Cyclin D1 and Ki-67 have associated with cell division. The aim of this study was to compare the expression of these markers in OSCC with and without cervical lymph node (LN) metastasis. Materials and Methods: This cross-sectional study was performed on 40 OSCCs with and without cervical LN metastasis (20 in each group) that was recorded in the pathology archive of Ayatollah Kashani Hospital in Isfahan. Clinical information including age, gender, and location was collected. Some histopathological parameters including depth of invasion, lymphovascular invasion (LVI), perineural invasion (PNI), number of LN metastases, histopathological grade, and stage of disease were evaluated. Immunohistochemical staining was performed for cyclin D1 and Ki-67. All data were entered into SPSS24 software and were analyzed by Mann-Whitney, Kruskal-Wallis, Chi-square, Fisher's exact, and t-tests. P < 0.05 was considered statistically significant. Results: Based on LVI and stage of disease, a significant correlation was found between the two groups (P < 0.001). There was a significant difference between the two groups based on cyclin D1 expression (P = 0.05). The expression of the Ki-67 showed a significant difference based on tumor location (P = 0.026) and PNI (P = 0.033). Conclusion: The use of markers should be considered in determining the prognosis of OSCC, and the cyclin D1 marker is one of the useful markers for predictors of cervical LN metastasis.

Evaluation of changes in Salivary Lactate Dehydrogenase Level for detection of Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis Study.

Background: Research has examined the relationship between salivary lactate dehydrogenase (LDH) levels and head and neck squamous cell carcinoma (HNSCC) screening and prognosis. Due to biochemical changes in cancer cells and increased production of lactate products in the body. The present systematic review aims to evaluate the changes in salivary LDH levels in HNSCC patients. Methods: The present study is a systematic review and meta-analysis. The data were collected by searching PubMed, Science Direct, Scopus, Web of Science, and Google Scholar from 2000 to 2021. The heterogeneity of the articles was analyzed using I2 and TAU2. Results: After searching the databases, of 988 articles, 665 duplicated articles were excluded by adopting the inclusion and exclusion criteria. So, 25 articles were primarily selected to be reviewed and evaluated for quality. Finally, 19 articles were selected and analyzed according to the Newcastle-Ottawa checklist. A total of 642 HNSCC patients were reviewed. The meta-analysis showed salivary LDH levels in the HNSCC group were higher than the control group (mean difference = 0.675, standard error = 0.058) (P < 0.001). Conclusions: As the research results showed, a significant correlation was observed between salivary LDH levels and HNSCCs. So, LDH can be employed as a valuable and minimally invasive biomarker in head and neck cancer screening and prevention.

Human papillomavirus in oral squamous cell carcinoma using p16 and its co-relationship with cervical lymph node metastasis and clinicopathological parameters.

Background: Due to the increasing prevalence of oral squamous cell carcinoma (OSCC) in Iran and especially in young people, this study aimed to identify human papillomavirus (HPV) using p16 in OSCC. Materials and Methods: In this descriptive-analytical cross-sectional study, 40 samples from the archives of the Pathology Department of Kashani Hospital were selected by a definitive diagnosis of OSCC with neck dissection. Demographic information including age, gender, location, and size of the lesion was obtained. Samples were divided into two groups based on lymph node (LN) metastasis. Immunohistochemical staining was performed for p16. Data were entered into SPSS 24 software and statistically analyzed by t-test, ANOVA, and Spearman nonparametric test. P <0.05 was statistically significant. Results: The mean age of patients was 59.7 ± 17.11 which in terms of age and gender there was no significant difference between the two groups including with and without cervical LN metastasis (P > 0.05). There was no significant difference between the two groups based on the grade of tumor, perninural invasion, tumor size and location (P > 0.05). The only significant difference between the two groups was based on lymphovascular invasion and disease stage (P < 0.05). The p16 expression also showed a significant difference between the two groups (P < 0.05). Conclusion: In OSCCs without cervical LN metastasis, a significant increase in p16 expression was observed compared to samples with cervical LNs metastasis. The presence of HPV was higher in samples with less LNs metastasis and possibly a better prognosis.

Evaluating the Clinicopathologic Parameters of Tongue Squamous Cell Carcinoma based on its Local Distribution.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common oral lesions and the tongue is one of the most common areas involved. The aim of this study was to evaluate the clinicopathologic feature of tongue SCCs based on its local distribution. Materials and Methods: In this cross-sectional study, clinical data such as age, gender, location, and clinical appearance were extracted from the archives of the Oral Pathology Department, Isfahan Dental School, registered with a definitive diagnosis of tongue SCC during 2005-2019. Then, 34 specimens were selected for histopathological evaluation in a simple random way. The histopathologic slides were examined to determine the grade of tumor malignancy. The data were entered into SPSS23 software and analyzed by Chi-square, Fisher exact, One-way ANOVA, and Non-parametric tests. P value <0.05 was considered significant. Results: Of the 275 OSCCs, 68 samples were tongue SCC. The mean age of patients was 61.7 ± 15 and 61.8% were women. The most common clinical manifestations were exophytic lesions (42.6%) and the most common site was the lateral border of the tongue (36.8%). The results did not show a significant relationship between the clinicopathologic feature including mean age (p = 0.766), gender (p = 0.338), clinical presentation (p = 0.434), grade of malignancy (p = 0.763) and location. But, among the histopathological parameters, the pattern of invasion (p = 0.047) was significantly associated with the local distribution. Conclusion: Given that most OSCCs had moderate differentiation of malignancy, identification of clinical features is needed. Attention to the pattern of invasion and location on the tongue can be effective in determining the therapeutic approach.

Evaluation of Epstein-Barr virus expression in oral squamous cell carcinomas.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common cancers. Epstein-Barr virus (EBV) has been related to throat-esophageal and gastric cancers. The aim of this study was to evaluate the prevalence of EBV in OSCC. Materials and Methods: This descriptive-analytical cross-sectional study was performed on 48 samples recorded in the archives of the Oral Pathology Department of Isfahan Dental School with definitive diagnosis of OSCCs prepared by excisional biopsy. Samples were selected in different age groups, locations, and genders. The grade of the tumor malignancy was determined based on Annreroth's classification. The EBV expression was determined by immunohistochemical (IHC) staining. The data were entered into SPSS software and statistically analyzed by t-test, Chi-square, and Fisher's exact test. Significance level was considered P < 0.05. Results: IHC staining for EBV was positive in 25 samples (52%). There was no significant relationship between EBV expression and mean age, gender, clinical feature, and grade of tumor differentiation (P > 0.05). A significant difference was observed between the EBV expression and location (P = 0.035). Furthermore, a significant difference was observed between the grade of tumor and staining intensity distribution index of EBV (P = 0.005). Conclusion: EBV expression was observed in most of the OSCCs, especially in poorly differentiated tumors. The pathogenesis of OSCCs may be related with EBV. OSCCs in buccal mucosa and floor of the mouth have more frequently of EBV expression. Future studies on the mechanisms of EBV and their role in OSCC are required with larger sample sizes.

Screening of oral squamous cell carcinoma by serum changes: A systematic review and meta-analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth common cancer in the world and 90% of oral malignant tumors. The aim of this study was the investigation of changes in some metabolic elements of OSCC patients' serum. MATERIALS AND METHODS: In this study, international databases such as PubMed, Science Direct, Scopus, Web of Science, and National (Magiran, IranMedex) were searched from 1980 to 2019. To analyze the data, a random-effects model was used to combine the differences in the mean of studies in STATA Software (version 12). RESULTS: A total of 724 articles were found with initial searching that 474 duplicate articles, 228 articles were excluded by reviewing the title and abstracts, and 17 articles were excluded from the study due to lack of inclusion criteria. Finally, five articles entered the meta-analysis phase. The mean difference value for zinc concentration of blood serum was 2.01 (95% confidence interval (CI): 0.36-3.66) and for copper was 1.04 (95% CI: 0.01-2.07). In both populations, the heterogeneity was found between studies (I 2 = 97.4, P < 0.001). CONCLUSION: Probably higher serum levels of copper and zinc could be one way to help to do a primary screening of OSCC in suspected patients.

The efficacy of photodynamic therapy in rat tongue dysplasia.

BACKGROUND: Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) has previously shown promising results in cancerous cell destruction. The present study was conducted to evaluate the efficacy of this treatment option on oral epithelial dysplasia in Wistar rats. Furthermore, microscopic effects of systemic versus topical administration of ALA before laser illumination was assessed. MATERIAL AND METHODS: Thirty male Wistar rats (200- 250 grams) were used in the present study. Tongue dysplasia was induced by a daily delivery of a 20 ppm solution of 4-nitroquinoline -1- oxide (4NQO) for 3 months. Then, rats were divided into 3 groups of 10 including, group 1 that was received systemic ALA-based PDT (30 mg/kg ALA), group 2 that was received topical ALA-based PDT (20% ALA solution) and group 3 (control) which was left untreated. Tongue specimens were fixed for histopathological evaluation and dysplasia was graded at microscopic level. Data was compared between various treatment groups using Mann Whitney test (p<0.05). RESULTS: The rate of atypical dysplastic cells was decreased significantly in both topical (p= 0.006) and systemic (p= 0.001) treatment groups compared to control group. Furthermore, systemic use of ALA resulted in a remarkable destruction of dysplastic cells compared to its topical application (p=0.045). Nevertheless, some evidence of muscle destruction was documented in systemic ALA group. CONCLUSIONS: It seems that ALA mediated PDT is an effective treatment option for the destruction of dysplastic cells. However, the extent of this effect depends on the mode of ALA administration before light illumination. Key words:Photodynamic therapy, 5-aminolevulinic acid, Dysplasia, Potentially malignant disorders.

Comparative Evaluation of the Efficacy of Laser Therapy and Fibroblastic Growth Factor Injection on Mucosal Wound Healing in Rat Experimental Model.

Introduction: The aim of the present study was to compare the effects of laser and basic fibroblastic growth factor (bFGF) treatment on operative wound healing in a rat model. Methods: Sixty-six male Wistar rats were employed in this study. A 10-mm surgical wound was created on the buccal mucosa of each rat, under anesthesia, and then the rats were divided into 3 groups of 22: (1) GF group (received subcutaneous injection of bFGF), (2) laser group (treated with low-level laser irradiation), and (3) control group (received no treatment). On day 5, half of the rats in each group and on day 10 the other half, were sacrificed. Afterward, samples were taken from rats' buccal mucosa for histological assay and scoring. The data were analyzed using MannWhitney test (α =5%). Results: On day 5 there was not any significant difference between GF and control groups; however, the laser group showed clinically delayed wound coverage, compared to other groups (P<0.05). On day 10, histological examination demonstrated marked vascular granulation tissue ( GT) in GF group. Collagen production was significantly prominent in laser group compared to GF treated samples (P=0.004). Inflammation of GT in GF and laser groups was significantly less than that in control samples (P=0.005 and P=0.001, respectively). Conclusion: The components of wound matrix induced by GF and laser treatment were significantly different. Although bFGF or laser treatment of oral wounds, under the conditions of the present study, did not accelerate wound healing, they showed some other notable effects on the quality of healing.

A case of central mucoepidermoid carcinoma associated with dentigerous cyst.

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland neoplasm. Central MEC (CMEC) is a rare primary intraosseous bony lesion with an incidence of 2%-4.3% of all MECs reported. In this article, we present a rare case of a CMEC in the anterior region of maxilla at a 43-year-old female patient that was arising from a dentigerous cyst. CMECs are extremely rare tumor. They are usually low-grade lesions with favorable prognosis. Odontogenic cysts are one of the origins of this lesion. Treatment of impacted tooth is necessary in the early stage for prevention of this neoplasm.

Rare and Extensive Malignant Melanoma of the Oral Cavity: Report of Two Cases.

Primary oral melanomas are uncommon malignant neoplasm of melanocytes origin. The most common site of oral melanoma is maxillary gingiva and hard palate. Oral mucosal melanoma exhibit a pathobiological behavior and clinical features different from cutaneous melanomas. Oral melanomas are often clinically silent which may consequently result in delayed diagnosis; thus, making the prognosis extremely poor. This case report presents clinical, histopathological and immunohistochemical features of two cases of advanced oral melanoma, one pigmented or melanotic melanoma in a 46-year-old female and another amelanotic melanoma in a 59-year-old male patient, with chief complaint of swelling in oral mucosa. Most oral melanomas are usually asymptomatic lesions with quick growing. Thus, the most cases are detected in late stage of diagnosis. Early diagnosis with careful examination by dentists, and early biopsy of pigmented and suspicious non-pigmented lesions would have an imperative role in more survival rate and better prognosis.

Minichromosome maintenance-2 (MCM2) expression differentiates oral squamous cell carcinoma from pre-cancerous lesions.

BACKGROUND: Proteins necessary for DNA replication and normal regulation for the cell cycle include minichromosome maintenance-2 (Mcm-2). Overexpression of this protein in several premalignant and malignant lesions has been observed. In this study, the diagnostic value of Mcm-2 expression in distinguishing histologically-proven normal oral mucosa (NOM), oral benign keratosis (OBK), oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC) was investigated. MATERIALS AND METHODS: In this descriptive analytical study, 73 archived specimens of oral tissues, including 20 OBK, 20 OED, 20 OSCC, and 13 NOM cases were selected. The means of labeling indices (LIs) of Mcm-2 expression by immunohistochemistry in each category of lesions were calculated. The data was analyzed by one-way ANOVA, discriminant analysis, and Fisher's exact tests. RESULTS: The means of labeling indices (LIs) of Mcm-2 expression show statistically significant difference between the four studied groups (P<0.001). Mcm-2 had overexpression and higher positivity in OSCCs. A cut-off point of 67% was determined in order to distinguish OSCC from precancerous lesions. CONCLUSION: The findings indicated that Mcm-2 could be a useful marker for early detection of oral SCC and dysplasia. Also, due to the overexpression of this marker in OSCC, there exists the possibility of application of Mcm-2 for molecular target therapy in these patients.

Clinicopathological study of 229 cases of salivary gland tumors in Isfahan population.

BACKGROUND: Salivary gland tumors are relatively uncommon and they consist of 3-10% of head and neck neoplasms. Most of studies have shown geographic variation in the incidence and histopathologic types of salivary gland neoplasms. The aim of this study was to evaluate the salivary gland tumors in Isfahan for 10 years duration. MATERIALS AND METHODS: In this epidemiological study, 229 medical records of patients with salivary gland neoplasms in Isfahan for 10 years duration (January 2001-December 2011) were reviewed. The clinical data and histopathological features were statistically analyzed using the Chi-square, analysis of variance and Fisher tests; P < 0.05 was considered to be significant. RESULTS: The data showed that salivary gland tumors were most frequent in women. The mean age of patients with benign tumors was 41.26 years and 51.83 years in malignant tumors. Out of 229 salivary gland neoplasms, 127 (55.5%) were benign and 102 (44.5%) were malignant. Most were in parotid (105), followed by the minor salivary glands (95), the submandibular gland (28) and the sublingual gland (1). CONCLUSION: Pleomorphic adenoma is the most common salivary gland tumor and mucoepidermoid carcinoma followed by adenoid cystic carcinoma are the most common malignancy of salivary gland tumors in Isfahan population. Although most of the results of this study were similar to those reported in other populations, some differences were observed.

Investigation of clinicopathological parameters alongside with p53 expression in primary and recurrent keratocysticodontogenic tumours.

BACKGROUND: Keratocysticodontogenic tumor (KCOT) is one of the most common odontogenic cysts and has a high recurrence rate after various treatment methods. Some studies have been conducted to identify the predictive factors of recurrence. In this study, the clinicopathological and immunohistochemical features of primary and recurrent KCOTs are analyzed, including immunohistochemically expression of p53 protein in cyst-lining epithelial cells in order to find more markers to predict the specific behaviour and greater tendency for recurrence. METHODS: In this descriptive analytic study, a total of 78 archived specimens of KCOTs, including 52 primary KCOT with no registered recurrences to date and 26 recurrent KCOT were selected. The clinical data and histopathological features of the epithelial lining and connective tissue wall were analyzed. Immuonohistochemical staining intensity distribution (SID) score for p53-positive cells were calculated for both groups. Results were analyzed by T-test, Chi-square, and Fisher's exact test. RESULTS: There were no statistically significant differences between primary and recurrent cases in terms of age (P = 0.181), gender (P = 0.744), and anatomical location (P = 0.294). In the histopathological assessment, epithelial budding (P = 0.001), daughter cysts (P = 0.013), and odontogenic rests (P = 0.036) were significantly more common in recurrent KCOTs. Immunohistochemical staining for p53 show statistically significant difference between the two groups (P = 0.041). CONCLUSION: In this study, some predictive factors of recurrence of KCOTs such as epithelial budding, daughter cyst and odontogenic rests were found. Furthermore, the evaluation of p53 expression in KCOT at the time of diagnosis was helpful for the prediction of recurrence.

Investigation of clinicopathological parameters alongside with p53 expression in primary and recurrent keratocysticodontogenic tumours

Keratocysticodontogenic tumor (KCOT) is one of the most common odontogenic cysts and has a high recurrence rate after various treatment methods. Some studies have been conducted to identify the predictive factors of recurrence. In this study, the clinicopathological and immunohistochemical features of primary and recurrent KCOTs are analyzed, including immunohistochemically expression of p53 protein in cyst-lining epithelial cells in order to find more markers to predict the specific behaviour and greater tendency for recurrence.