Occludin and claudin-1 are potential prognostic biomarkers in patients with oral squamous cell carcinomas: An observational study.

OBJECTIVES: The objective of this study was to evaluate the expression of several cell membrane markers in oral squamous cell carcinomas (OSCC) and to examine their prognostic influence. STUDY DESIGN: We analyzed the immunohistochemical expression of claudin-1 (CLDN-1), claudin-4 (CLDN-4), claudin-5 (CLDN-5), claudin-7 (CLDN-7), occludin (OCLN), and E-cadherin (CDHE) in 60 patients with OSCC treated in a central hospital Center of Oporto. The prognostic significance of these biomarkers in cancer-specific survival and recurrence-free survival were evaluated using multivariate analysis. RESULTS: Claudin-1 was observed in the membrane of tumor cells in 51 cases (89.5%), CLDN-4 in 36 cases (63.2%), and CLDN-7 in 48 cases (80%). Claudin-5 was detected in the cytoplasm of tumor cells in 46 cases (78%) and OCLN in 40 cases (70.2%). In a multivariate analysis, the combined evaluation of OCLN and CLDN-1 revealed a significant and independent association with cancer-specific survival and recurrence-free survival. We found a low extent score for OCLN and a high intensity score for CLDN-1, presenting the hazard ratios of 15.48 (P = .014) and 9.446 (P = .012), respectively. CONCLUSION: The CLDN-1 and OCLN proteins could be involved in tumor progression of OSCC. Their combined deregulated expression showed an adverse effect on survival and therefore they could be regarded as important prognostic biomarkers in OSCC.

Podoplanin Expression Independently and Jointly with Oral Epithelial Dysplasia Grade Acts as a Potential Biomarker of Malignant Transformation in Oral Leukoplakia.

Our aim was to evaluate the expression of biomarkers, CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin in oral leukoplakias (OL) and to assess their potential for prediction of malignant transformation (MT). We analyzed the expression of CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin by immunohistochemistry in 52 OL, comprised of 41 low-grade (LG) dysplasia and 11 high-grade (HG) cases. Twelve healthy normal tissues (NT) were also included. Univariate and multivariate analysis were performed to evaluate any association with MT. Variable expression among the studied markers was observed, with a significant increase of high expression from NT to LG and HG cases in CD44v6 (p = 0.002), P53 (p = 0.002), P73 (p = 0.043), and podoplanin (p < 0.001). In multivariate analysis, cases with high podoplanin score showed a significant increased risk of MT (HR of 10.148 (95% CI of 1.503−68.532; p = 0.017). Furthermore, podoplanin combined with binary dysplasia grade obtained a HR of 10.238 (95% CI of 2.06−50.889; p = 0.004). To conclude, CD44v6, p53, p73, and podoplanin showed an increasing expression along the natural history of oral carcinogenesis. Podoplanin expression independently or combined with dysplasia grade could be useful predictive markers of MT in OL.

Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study / Expresión de las proteínas del punto de control del ensamblaje del huso BubR1 y Mad2 expresión como posibles biomarcadores de transformación maligna de la boca leucoplasia: un estudio de cohorte observacional

Background: The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the ac-curacy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oralcarcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia.Material and Methods: We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64oral biopsies from 52 oral leukoplakias and 12 normal tissues. Univariate and multivariate analysis were per-formed to evaluate predictive factors for malignant transformation (MT).Results: We observed that BubR1 and Mad2 were more highly expressed in high dysplasia grade lesions than inlow grade or normal tissues (P<0.05). High expression of Spindly was significantly correlated with a high Ki-67score (P=0.004). Six (11.5%) oral leukoplakias underwent malignant transformation. In univariate analysis, thebinary dysplasia grade (high grade) (P<0.001) was associated with a higher risk of malignant transformation aswell as high BubR1 (P<0.001) and high Mad2 (P=0.013) expression. In multivariate analysis, high expression ofBubR1 and Mad2 when combined showed an increased risk for malignant transformation (P=0.013; HR of 4.6,95% CI of 1.4-15.1). Conclusions: Our findings reveal that BubR1 and Mad2 were associated with an increased risk for malignant trans-formation independently of histological grade and could be potential and useful predictive risk markers of malignanttransformation in oral leukoplakias.(AU)

An observational retrospective study of odontogenic cyst´s and tumours over an 18-year period in a Portuguese population according to the new WHO Head and Neck Tumour classification / Un estudio observacional retrospectivo de quistes y tumores odontogénicos durante un período de 18 años en una población portuguesa según la nueva clasificación de la OMS para los tumores de cabeza y cuello

Background: Odontogenic cysts and tumours of the jaws represent one of the most prevalent groups of oral-maxillofacial lesions. We aimed to evaluate the clinical and pathological characteristics of a cohort of odontogeniccysts (OC) and odontogenic tumours (OT) of the jaws in a Portuguese population.Material and Methods: This observational retrospective study analysed patients diagnosed with either an OC orOT of the jaws at a central hospital of Oporto, Portugal, between 1988 and 2006. Data collected from patients’files included demographic, clinical, radiological and histopathological information. Recurrence was evaluatedusing univariate and multivariate analysis.Results: The sample consisted of 397 patients, 231 males (58.2%) and 166 females (41.8%), with a mean-ageof 36.7±17 years. Twenty-seven patients (6.8%) presented with more than one lesion providing a total of 433lesions. There were 396 (91.5%) OC, mostly represented by radicular cysts (n=257;59.4%), dentigerous cysts(n=79;18.2%), or odontogenic keratocysts (n=50;11.5%). There were 37 (8.5%) OT, mostly represented by amelo-blastomas (n=16;3.7%), and odontomas (n=9;2.1%). The most common initial clinical manifestation was swelling (n=224;51.7%). Recurrence was observed in 30 cases (6.9%), mostly in ameloblastomas (n=6;37.5%) and odontogenickeratocysts (n=12;24%). In the multivariate analysis the diagnosis classification of the lesion was the only indepen -dent and significant variable related with the recurrence (P=0.04).Conclusions: Radicular cysts were the most commonly occurring type of OC and ameloblastomas the most com-monly occurring OT. Amelobastomas and odontogenic keratocysts were the lesions with the highest rates of recur-rence. This large sample provides useful information about the frequency profile and characteristics of OC and OTover a period of 18 years, allowing valuable comparison with data from other countries.(AU)

Spindly and Bub3 expression in oral cancer: Prognostic and therapeutic implications.

OBJECTIVES: Bub3 and Spindly are essential proteins required for the activation and inactivation of the spindle assembly checkpoint, respectively. Here, we explored the clinicopathological significance and the therapeutic potential of the opposing roles of the two proteins in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Bub3 and Spindly expression was evaluated by immunohistochemistry in 62 tissue microarrays from OSCC and by real-time PCR in OSCC cell lines and in normal human oral keratinocytes. The results were analyzed as to their clinicopathological significance. RNA interference-mediated Spindly or Bub3 inhibition was combined with cisplatin treatment, and the effect on the viability of OSCC cells was assessed. RESULTS: Overexpression of Bub3 and Spindly was detected in OSCC patients. High expression of Spindly, Bub3, or both was an independent prognostic indicator for cancer-specific survival and was associated with increased cellular proliferation. Accordingly, Bub3 and Spindly were upregulated in OSCC cells comparatively to their normal counterpart. Inhibition of Bub3 or Spindly was cytotoxic to OSCC cells and enhanced their chemosensitivity to cisplatin. CONCLUSIONS: The data point out Bub3 and Spindly as potential markers of proliferation and prognosis, and highlight the potential therapeutic benefit of combining their inhibition with cisplatin.

Post-tooth extraction bacteraemia: a randomized clinical trial on the efficacy of chlorhexidine prophylaxis.

OBJECTIVES: To investigate the development of post-extraction bacteraemia (PEB) after the prophylactic use of chlorhexidine (CHX). PATIENTS AND METHODS: A total of 201 patients who underwent a tooth extraction were randomly distributed into four groups: 52 received no prophylaxis (CONTROL), 50 did a mouthwash with 0.2% CHX before the tooth extraction (CHX-MW), 51 did a mouthwash with 0.2% CHX and a subgingival irrigation with 1% CHX (CHX-MW/SUB_IR) and 48 did a mouthwash with 0.2% CHX and a continuous supragingival irrigation with 1% CHX (CHX-MW/SUPRA_IR). Peripheral venous blood samples were collected at baseline, 30 seconds after performing the mouthwash and the subgingival or supragingival irrigation, and at 30 seconds and 15 minutes after completion of the tooth extraction. Blood samples were analysed applying conventional microbiological cultures under aerobic and anaerobic conditions performing bacterial identification of the isolates. RESULTS: The prevalences of PEB in the CONTROL, CHX-MW, CHX-MW/SUB_IR and CHX-MWSUPRA_IR groups were 52%, 50%, 55% and 50%, respectively, at 30 seconds and 23%, 4%, 10% and 27%, respectively, at 15 minutes. The prevalence of PEB at 15 minutes was significantly higher in the CONTROL group than in the CHX-MW group (23% versus 4%; p = 0.005). At the same time, no differences were found between CONTROL group and CHX-MW/SUB_IR or CHX-MW/SUPRA_IR groups. Streptococci (mostly viridans group streptococci) were the most frequently identified bacteria (69-79%). CONCLUSIONS: Performing a 0.2% CHX mouthwash significantly reduces the duration of PEB. Subgingival irrigation with 1% CHX didn't increase the efficacy of the mouthwash while supragingival irrigation even decreased this efficacy, probably due to the influence of these maneuvers on the onset of bacteraemia. CLINICAL RELEVANCE: These results confirm the suitability of performing a mouthwash with 0.2% CHX before tooth extractions in order to reduce the duration of PEB. This practice should perhaps be extended to all dental manipulations. TRIAL REGISTRATION: Clinicaltrials.gov NCT02150031.

EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survival.

The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P = 0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression (P = 0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS) (P = 0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

Phosphorylated mammalian target of rapamycin is associated with an adverse outcome in oral squamous cell carcinoma.

OBJECTIVES: To evaluate the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and phosphatase and tensin homolog deleted on chromosome TEN (PTEN) in oral squamous cell carcinomas (OSCCs) and relate them with clinicopathologic characteristics and outcome. STUDY DESIGN: We analyzed p-mTOR and PTEN protein expression by immunohistochemistry in 72 OSCCs. Multivariate analysis was conducted to examine their role in survival. RESULTS: p-mTOR expression was observed in 46 (63.9%) cancers and PTEN expression was absent in 22 (30.6%). An adverse independent prognostic value for high p-mTOR expression was found (P = .043) as well as for advanced tumor stage (P = .010) in patients' overall survival (OS). For disease-free survival (DFS), only advanced tumor stage (P = .001) presented an adverse independent prognostic value. CONCLUSIONS: The effect of p-mTOR in OS of OSCC suggests that this marker may serve as a reliable biological marker to identify high-risk subgroups and as a guide to therapy. Furthermore, the high expression of p-mTOR suggests that this protein may be a promising therapeutic target in OSCC.

General anesthesia increases the risk of bacteremia following dental extractions.

OBJECTIVE: The influence of oral health status, the number of teeth extracted, and the anesthetic modality used is currently a matter of debate in the prevalence of bacteremia following dental extractions (BDE). The aim of the present study was to analyze the factors affecting the prevalence, duration, and etiology of BDE. STUDY DESIGN: Blood samples were collected from 210 patients at baseline, 30 seconds, 15 minutes, and 1 hour after performing dental extractions. Samples were processed in the Bactec 9240 and the subculture and further identification of the isolates were performed using conventional microbiological techniques. RESULTS: The prevalence of BDE at 30 seconds, 15 minutes, and 1 hour were 71%, 45%, and 12%, respectively. In the multivariate analysis, the "anesthetic modality" (local anesthesia versus general anesthesia) was the only variable related to BDE. CONCLUSION: General anesthesia represents a risk factor for BDE, increasing its prevalence and duration.

Usefulness of labial salivary gland biopsy in familial amyloid polyneuropathy Portuguese type.

BACKGROUND: The diagnosis of amyloidosis of all types is definitively made by demonstration of Congo red binding material in the affected tissues. Nerve biopsy was classically used to diagnose amyloid polyneuropathy but less invasive alternative types of biopsies have been proposed including labial salivary gland (LSG) biopsy, a minimally invasive procedure. METHOD: LSG biopsies were done in 87 subjects with molecular diagnosis of TTRVal30Met mutation. The group includes 76 patients in different stages of familial amyloid polyneuropathy and 11 asymptomatic carriers. They were all submitted to a stomatological and a neurological observation to evaluate oral health problems and to determine the neurological stage of the disease. No major oral health problems were found. Mean age of onset of the symptomatic disease was 32.8 years (+/-9.69 SD). CONCLUSIONS: No significant side effects occurred after the surgical procedure, and adequate material for pathological analysis was always obtained. Amyloid deposition was found in 91% of the patients. Patients with negative biopsies (N = 7) were all in the earlier stage of the disease. Two asymptomatic carriers had biopsies with amyloid deposition. We conclude that LSG biopsy is a useful, sensitive and minimal invasive method to detect amyloid deposition.

Odontogenic cysts: a descriptive clinicopathological study

Odontogenic cysts are lesions that deserve every attention, mainly because of all complications they can cause. To study their characteristics, the authors did a retrospective clinicopathological analysis of 124 oral biopsies that were diagnosed as odontogenic cysts, in Hospital Geral de Santo António - Porto. Clinical variables such as age, sex, location, clinical diagnosis and histological diagnosis were studied. Inflammatory radicular cysts were the most commons (48.4%) followed by dentigerous cysts (21.0%), residual cysts (17.7%)and keratocysts (12.1%). The most frequent clinical manifestation was swelling (62.9%). Age appears to be related to the type of cyst, expressing the etiopathologic characteristics of each one. It is concluded that a definitive diagnosis is based on a triad of radiology, clinics and histology, which presupposes a tight cooperation between the clinician and the histopathologist