Luís Silva Monteiro

Spectrum of epilepsy in neurocysticercosis: a long-term follow-up of 143 patients

To characterize the clinical profile and the prognostic factors of the epilepsy due to parenchymal neurocysticercosis (NCC) 143 patients were analysed. Patients (62 men, 81 women) had a mean age at epilepsy onset of 29 years (range 2‐71), mean epilepsy duration of 16 years (range 1‐58) and mean follow‐up of 5.2 years. Seizures were generalised tonic‐clonic (GTC) in 50 patients (35%), simple partial (SP) in 66 (46%) and complex partial (CP) in 27 (19%). Epilepsy began as a single seizure in 73% and as a cluster of seizures or status epilepticus in 27%. Seizures were controlled in 64% of patients. Multivariate analysis revealed that significant prognostic factors associated with seizure control were type of seizures and age at epilepsy onset. Control is more likely in GTC and SP seizures and in patients with a higher age at seizures onset. Our analysis establishes that epilepsy due to NCC is a heterogeneous syndrome concerning age and mode of onset, seizure type, duration of epilepsy and pattern of evolution probably related with different pathogenic mechanisms.

Incidence rates and trends of lip, oral and oro-pharyngeal cancers in Portugal

OBJECTIVES To analyse the trends and patterns of lip, oral and oro-pharyngeal cancer incidence in Portugal between 1998 and 2007. PATIENTS AND METHODS Data on lip, oral and oro-pharyngeal cancers was collected from the databases maintained at the three main Regional Cancer Registries of Portugal (1998-2007). The data were analysed by gender, age and by site. Incidence rates were age standardized by the direct method, and joinpoint regression was used to estimate trends in incidence. RESULTS During this 10-year period, a total of 9623 cases of lip, oral and oropharynx cancers were reported, 7565 (78.6%) in males and 2058 (21.4%) in females. There was an increase in the age-standardized incidence of oral cancers by 1.96% per year for both sexes grouped together and an increase of 4.34% per year for the female group. Oro-pharyngeal cancer showed an increase incidence trend of 3.49% per year for both sexes grouped together and an increase of 3.49% per year for male group among the sites analysed. Lip cancer showed a decrease in its incidence rate. CONCLUSION In view of rising trends, it is necessary to implement policies on oral cancer control by initiating campaigns on oral cancer awareness and screening and to harness political measures on tobacco and alcohol control for the Portuguese population.

Epidermal growth factor receptor immunoexpression evaluation in malignant salivary gland tumours

OBJECTIVE The aim of this study was to determine epidermal growth factor receptor (EGFR) expression in malignant salivary gland tumours and its possible relationships with clinical and morphological findings, disease course and prognosis. PATIENTS AND METHODS The study sample comprised 88 patients diagnosed and treated for primary malignant salivary gland tumours between January 1992 and December 2002. We analysed EGFR expression using immunohistochemistry on formalin-fixed, paraffin embedded surgical specimens of all patients. Statistical analysis was used to investigate possible relationships between EGFR expression and clinical findings, histological findings, disease course and patients survival. RESULTS Of all cases, 32 (36.4%) were EGFR positive. There was a statistically significant correlation between EGFR expression and histological grade. No other variable was correlated with EGFR expression including the overall and disease-free survival. Stage classification was the only parameter in multivariate analysis that was an independent predictor of low overall and disease-free survival. CONCLUSION EGFR is not a useful indicator of prognosis in malignant salivary gland tumours. However, the EGFR expression in salivary gland cancers like adenocarcinomas, undifferentiated carcinomas, mucoepidermoid carcinomas or salivary duct carcinomas suggests that these tumours may be a candidate for therapy investigation directed at EGFR.

EGFR and Ki-67 expression in oral squamous cell carcinoma using tissue microarray technology

OBJECTIVE Our aim was to validate the use of tissue microarrays (TMA) in oral squamous cell carcinomas (OSCC) to analyse epidermal growth factor receptor (EGFR) and Ki-67 expression. We also analysed the relationship that the expression of these markers may have with clinical, pathological and survival variables. PATIENTS AND METHODS The study sample comprised 39 unselected patients diagnosed and treated for OSCC. We analysed Ki-67 and EGFR expression by immunohistochemistry on formalin-fixed, paraffin-embedded surgical specimens. Whole sections (WS) were compared with double 1.5 mm core-tissue microarrays. RESULTS High EGFR expression was observed both on TMA (in 98% of the cases) and WS (in 100% of the cases) with substantial agreement kappa value (0.720). EGFR expression was not significantly associated with clinical, pathological and survival variables on TMA and WS. Ki-67 analysis showed a Spearman correlation of 0.741 with a Ki-67 mean labelling index of 45% in TMA and 56.8% in WS. We found a significant relationship between gender and Ki-67 labelling index on WS (P = 0.022) and TMA (P = 0.002). Clinical stage was the only parameter in multivariate analysis that had a significant predictive value. CONCLUSION We demonstrate that dual 1.5 mm core TMA is a valid, rapid, economical and tissue-saving way to study OSCC biopsies and that it presents strong correlation with the WS. EGFR overexpression in OSCC suggests that these tumours may be a candidate for therapy investigation directed to EGFR.

Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor prognostic marker in early stage oral squamous cell carcinoma

OBJECTIVE Our aim was to evaluate the expression of several molecules that regulate growth, the cell cycle and signalling pathways including EGFR, p53, p16 and p27 in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic markers by relating to clinicopathological characteristics and the clinical outcome. PATIENTS AND METHODS Using tissue microarray technology, we analysed 67 primary OSCC and examined immunohistochemical expression of EGFR, p53, p16 and p27. Multivariate analysis was conducted to examine their role in survival. RESULTS Many of the markers were highly expressed in these cancers. Membranous EGFR expression in 95.2%, both membrane and cytoplasm expression in 35%, p53 expression in 61.6%, p27 expression in 89.5% and p16 expression in 27.9% of cases. In the multivariate analysis, independent prognostic influence of a lower overall survival was determined only for advanced tumour stage (P < 0.001), p53 overexpression (P = 0.004), EGFR cytoplasm and membrane co-expression location (P = 0.002) and p16 reduced expression (P = 0.002). When considering a subgroup of early stage tumours, p53 overexpression (P = 0.028) and combined membranous and cytoplasm EGFR co-expression (P = 0.039) were indicators of a lower overall survival. For disease-free survival, in addition to these three factors, the histological grade (P = 0.011) showed independent prognostic values. CONCLUSION The independent value of EGFR subcellular location (cytoplasm and membrane) and p53 overexpression in overall survival even in early stages of OSCC suggests that these markers may serve as reliable biological markers to identify high-risk subgroups and to guide therapy.

High CDC20 expression is associated with poor prognosis in oral squamous cell carcinoma

OBJECTIVES Human Cell Division Cycle 20 (CDC20) homolog is a crucial target of the spindle assembly checkpoint. It is an activator of the Anaphase-Promoting Complex/Cyclosome (APC/C) which promotes anaphase onset and mitotic exit through the ubiquitination of securin and cyclin B1. Overexpression of CDC20 was previously reported in oral squamous cell carcinoma (OSCC). Here, we propose to explore the clinicopathological significance of CDC20 overexpression and its potential use as a prognostic marker in OSCC. METHODS Using tissue microarray technology, we analyzed CDC20 expression in 65 primary OSCC tissues by immunohistochemistry. Statistical analysis was performed to evaluate the clinicopathological and prognostic significance of CDC20 expression in OSCC. RESULTS Of the 65 cases of patients with OSCC studied, 37 (56.9%) showed high CDC20 protein expression. No clinicopathological features were correlated with CDC20 expression. Importantly, in univariable analysis, OSCC patients with higher CDC20 protein expression showed significantly shorter cancer-specific survival rate (P = 0.018). Multivariable analysis identified high CDC20 expression as an independent prognostic factor (P = 0.032). CONCLUSION High CDC20 expression is associated with poor prognosis in OSCC and may be used to identify high-risk OSCC patients and may serve as a therapeutic target.

Protective role of the HLA-A*02 allele in Portuguese patients with multiple sclerosis.

Background Multiple sclerosis (MS) is associated with human leukocyte antigen (HLA) HLA–DRB1*15. Recent evidence that CD8 T cells are implicated in MS suggests that HLA class I may also contribute. An association of HLA–A*02 and A*03 alleles has been described. Objectives We examined the influence of HLA–A*02 and HLA–A*03 in Portuguese patients with MS, independently of HLA–DRB1*15 using a logistic regression model. Conclusions DRB1*15 increased the risk of developing MS and HLA–A*02 decreased the risk. A*03 had no effect. To analyze if HLA–A*02 association was independent from DRB1*15, an interaction between these two alleles was introduced in the model; no significant interaction was found.

A clinical-pathological and survival study of oral squamous cell carcinomas from a population of the North of Portugal.

Objectives: Our aim was to analyze the clinical, pathological, and outcome characteristics of oral squamous cell carcinomas (OSCC) from a population of the north of Portugal. Material and Methods: We conducted a descriptive study of 128 OSCC diagnosed between the years of 2000 and 2010 in the Centro Hospitalar do Porto. Through of the review of the clinical records we studied several clinical, pathological, and outcome variables. The overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier method and log-rank test. Cox regression method was used for multivariate analysis. Results: Of 128 patients with OSCC, 83 (64.8%) were male and 45 (35.2%) were female, (mean age of 62.13±15.57 years). The most affected location was the tongue (n=52; 40.6%). The most common cause of reference was a non-healing ulcer (n=35; 28.9%) followed by oral pain (n=27; 22.3%). Sixty (60.6%) patients were tobacco consumers and 55 (57.3%) alcohol consumers. The cumulative 3-years OS rate was 58.6% and DFS was 55.4%. In multivariable analysis for OS, we found an adverse independent prognostic value for advanced tumour size (p<0.001) and for the presence of perineural permeation (p=0.012). For DFS, advanced stage tumours presented adverse independent prognostic value (p<0.001). Conclusions: OSCC occurred most frequently in males, in older patients, and in patients with tobacco and/or alcohol habits. TNM and tumour stage additionally to the perineural permeation were the most important prognostic factors for the survival of these patients, contributing to identify high-risk subgroups and to guide therapy. Key words:Squamous cell carcinoma, mouth neoplasms, oral cancer, oral pathology, prognosis.

Oral Cancer Awareness and Knowledge in the City of Valongo, Portugal

We conducted a questionnaire survey among 602 subjects in order to analyze the awareness and knowledge on oral cancer among residents of the city of Valongo in Portugal. The cancer that most subjects were aware of was breast cancer (99%). Oral cancer was the least mentioned cancer (68.6%). There was awareness of the relationship between oral cancer and smoking among 89.5% subjects, but less of the association with alcohol misuse (63.3%). Nonhealing mouth ulcers were identified as a sign or symptom of oral cancer by 90.0% and red or white patch by only 52.8% subjects. Whereas 94.5% agreed that early detection could improve the treatment outcome, a disheartening 28.1% believed that whether a person developed an oral cancer or not is a matter of luck and therefore is unavoidable. Surprisingly only 1.7% were ever submitted to or had knowledge of receiving a consultation regarding oral cancer. In conclusion, this survey demonstrates a general lack of awareness and knowledge on oral cancer in a population of Valongo. An oral health promotion strategy should involve elements of basic education on oral cancer for this population, and regular oral cancer screenings should be implemented in Valongo.

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.