[Posterior reversible encephalopathy syndrome in patients with preeclampsia: case report]. / Le syndrome d´encéphalopathie postérieure réversible en cas de pré-éclampsie: à propos d´un cas.

Reversible posterior encephalopathy syndrome (PRES) is a rare clinico-radiological syndrome. Diagnosis is suspected in pregnant women suffering from eclampsia when brain CT scan shows radiological images suggestive of this disease. We here report the case of a 25-year-old pregnant woman at 33 weeks' gestation with a history of pre-eclampsia presenting with convulsive seizures and high blood pressure following cesarean section. The patient was admitted to the Intensive Care Unit; clinical and radiological investigations revealed PRES syndrome. The clinical course was favorable after control of blood pressure by appropriate treatment and anticonvulsant therapy. Reversible posterior encephalopathy syndrome is a neurological manifestation rarely occurring in patients with pre-eclampsia, but it is not exceptional; then diagnosis should be suspected in patients with neurological signs. Brain MRI is the best diagnostic tool.

Quantitative measurement of iNOS expression in melanoma, nasopharyngeal, colorectal, and breast tumors of Tunisian patients: comparative study and clinical significance.

Chronic inflammation increases the risk of development of human malignancies. iNOS is an enzyme dominantly expressed during inflammatory reactions and seems to play a critical role in tumorigenesis. Our aim was to assess the iNOS expression in four types of human tumors: breast, colorectal, nasopharyngeal, and melanoma, of Tunisian patients. The level of iNOS was measured by RT-QPCR in tumor specimens. We showed that the expression of iNOS was higher in breast compared to colorectal and nasopharyngeal tumors, whereas in melanoma, the level of iNOS expression was low. Significant associations were found when comparing the iNOS expression in cancers pairs such as melanoma versus colorectal (p < 0.0001), colorectal versus nasopharyngeal (p = 0.0072), and melanoma versus breast (p < 0.0001). Furthermore, iNOS expression correlated with the Breslow thickness, Clark level, and histological subtype in melanoma, while in nasopharyngeal carcinoma, significant association was seen with age at diagnosis, TNM, metastasis, response to treatment, and expression of COX-2. Furthermore, the expression of iNOS correlated with tumor size, TNM, tumor location, and histological type in colorectal cancer, and with tumor size, tumor stage, SBR grade, and triple negative cases in breast cancer. On the other hand, immunohistochemistry analysis shows that the expression of iNOS is observed in the stroma and tumor cells as well. Overall, our results highlight that iNOS is a reliable marker for advanced stage and aggressive behavior for the four types of cancer and might be a potential promising therapeutic target.

Expression and mutation pattern of ß-catenin and adenomatous polyposis coli in colorectal cancer patients.

BACKGROUND AND AIMS: ß-Catenin and adenomatous polyposis coli (APC) are major components of the Wnt pathway. This study aimed to investigate the expression of ß-catenin and APC in tumors and lymph nodes in colorectal cancer (CRC) patients and the mutational spectrum of the genes coding these proteins. METHODS: Expression of APC and ß-catenin was examined in 124 tumors and 41 lymph nodes. Exon 3 of CTNNB1 and the mutation cluster region (MCR) in exon 15 of the APC gene were screened for mutation by PCR-sequencing. RESULTS: Nuclear/cytoplasmic immunostaining of ß-catenin was detected in 58.1 and 48.8% in tumors and lymph nodes, respectively. In tumors, abnormal expression of ß-catenin correlated with tumor size and with those in lymph nodes. Membranous ß-catenin expression occurred in 41.9 and 14.6% of tumors and lymph nodes, respectively. In tumors, lack of membranous ß-catenin correlated with high invasiveness and metastatic potential. Positive immunostaining for APC was observed in 2 and 14% of tumors and lymph nodes, respectively. Overexpression in nucleus/cytoplasm and lack of membranous ß-catenin significantly correlated with a reduced overall survival. Among 25 tumors, four harbour mutation in Ser33 and Ser47 and overexpress the ß-catenin in the nucleus/cytoplasm. Mutations were identified in the APC gene in 13 tumors and six mutations were novel. CONCLUSIONS: Positive association between aberrant expression of ß-catenin in the nucleus/cytoplasm of tumors and lymph nodes was observed. Nucleus/cytoplasmic accumulation of ß-catenin and loss of membranous expression are related to reduced survival and could serve as a candidate prognostic predictor.

Expression of p16INK4a, alone or combined with p53, is predictive of better prognosis in colorectal adenocarcinoma in Tunisian patients.

INTRODUCTION: Alterations in different signaling pathways are involved in initiation and progression of colorectal carcinoma, such as those related to p53, MLH1, p16INK4a, Kras, etc. AIM: This study was conducted with the aim to investigate the expression of p16INK4a and p53 in colorectal cancer (CRC) and evaluated their correlation with major clinicopathologic features and patients' survival. MATERIALS AND METHODS: The expression of p16INK4a and p53 were analyzed by immunohistochemistry on 70 paraffin specimens of CRC. RESULTS: Positive immunostaining for p16INK4a and p53 was observed in 27 (38.6%) and 53 (80%) cases, respectively. Significant correlation between loss of p16INK4a expression and tumor size was found (P=0.008), whereas overexpression of p16INK4a correlated with favorable prognosis parameters, such as absence of lymph node metastasis (P=0.029) and early stage of CRC (P=0.027). Furthermore, p53 overexpression significantly correlated with distal tumor location (P=0.022) and was related to a better overall survival in the group of patients with distal colon carcinomas (P=0.002). Patients with p16INK4a-positive tumors had a significant longer overall survival time than patients with p16INK4a-negative carcinomas (P=0.033). In addition, Cox regression model showed that overexpression of p16INK4a is an independent factor for prognosis with depth of invasion, p53 accumulation, and coincident abnormal expression of p16INK4a or p53. CONCLUSION: Our data suggest that the assessment of both p53 and p16INK4a expression might be helpful in predicting prognosis in patients with colorectal cancer.

Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic colorectal adenocarcinoma.

The methylation of CpG islands in the promoters is associated with loss of protein via repression of gene transcription. Several studies have demonstrated that tumour suppressor and DNA repair genes are often aberrantly hypermethylated in colorectal cancer. The present study was conducted to examine whether the methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters was associated with clinical features and patients' survival in CRC (colorectal carcinoma). Aberrant methylation of p16INK4a and hMLH1 promoters was found in 47.2 and 53.4% of tumours respectively. For adjacent non-tumoral mucosa, p16INK4a was fully unmethylated in 30% of the cases, whereas hMLH1 was predominantly unmethylated (76%). Methylation of p16INK4a correlated with gender and tumour size (P=0.005 and 0.035 respectively), whereas those of hMLH1 significantly correlated with overall survival (P log rank=0.007). Concomitant methylation of p16INK4a and hMLH1 was associated with TNM (tumour, lymph node and metastases) stage and tumour size (P=0.024 and 0.021 respectively). Our data show that loss of hMLH1 expression through aberrant methylation could be used as a marker of poor prognosis in CRC.

Hypermethylation of RARß2 correlates with high COX-2 expression and poor prognosis in patients with colorectal carcinoma.

Silencing of gene expression by aberrant methylation at the CpG islands is common in human tumors, including colorectal cancer. This epigenetic alteration affects promoter of genes having crucial cellular functions such as tumor suppressor, DNA repair, apoptosis, cell adhesion, etc. We investigated the methylation status in the promoter regions of the RARß2, RASSF1A, DAPKinase, and CDH1 genes in 73 colorectal carcinoma and 43 paired normal tissues of Tunisian patients using methylation-specific PCR assays. The association between methylation status and the clinicopathological features was evaluated. To determine whether aberrant methylation affects gene expression, we performed immunohistochemistry analysis for E-cadherin and COX-2, a target gene of RARß2. The methylation frequencies vary from 80.8% for RARß2 to 35.6% for RASSF1A while in non-tumor-paired samples; the frequencies of methylation are significantly lower for all the fourth genes tested. The methylation status did not correlate with any of the clinical features considered; however, aberrant methylation of RARß2 was associated with a shortened overall patients' survival (p log rank = 0.026); nevertheless, it needs to be confirmed on larger sample size. Moreover, a significant inverse association was observed between methylation status of RARß2 and COX-2 protein expression in tumor specimen (p = 0.014). On the other hand, we found that loss of E-cadherin expression was significantly associated with aberrant methylation of the CDH1 promoter (p = 0.005). Our findings showed that RARß2 was frequently methylated in colorectal cancer and correlated with a worse prognosis and high expression of COX-2 suggesting a link between these two proteins in colorectal carcinogenesis. We also showed that epigenetic alteration of CDH1 is a major mechanism of the loss of E-cadherin protein expression in primary colorectal tumors.