Consensus guidelines for the diagnosis and treatment of multiple sclerosis.

The diagnosis of multiple sclerosis (MS) is dependent on the presence of clinical and paraclinical evidence demonstrating dissemination of central nervous system lesions in both space and time, as well as the exclusion of other disorders. Diagnostic criteria were originally promulgated in 1965 by the Schumacher committee and modified subsequently by the Poser committee to include paraclinical evidence. The most recent criteria are the 2010 modifications of the 2001 McDonald criteria, which are focused on making an earlier diagnosis of MS. This article provides guidelines, derived from clinical experience as well as evidence-based medicine, for the diagnosis and management of MS with special emphasis on practices in the Middle East.

Mutations in exons 6 and 7 of TP53 gene correlate positively with serum tumor necrosis factor alpha independent of microsatellite instability in BAT26 gene in Egyptian patients with endometrial carcinoma.

UNLABELLED: Abnormalities in the TP53 gene are the most frequent genetic alterations in human cancers. The role and mechanism of TP53 mutations have been well studied in many types of human cancer. Similarly, the presence of microsatellite instability (MSI) in the DNA mismatch repair system (hMSH2) may provide evidence of faulty DNA mismatch repair. One of the most important locations of MSI is the BAT26 gene. In addition, deranged serum cytokines, especially elevated levels of the tumor necrosis factor (TNF) alpha, have been found in many gynecological conditions. AIMS: The current study aimed at evaluating mutations in exons 6 and 7 of TP53 and the presence of microsatellite instability in BAT26 of the hMSH2 system in Egyptian patients with endometrial carcinoma. The study also evaluated whether there was a correlation between any of these genetic mutations/instability and the tissue expression of estrogen and progesterone receptors and the serum TNF-alpha level. PATIENTS AND METHODS: The current study included 2 groups: a control group comprising 20 healthy women aged 52.21 +/- 5.80 years attending the clinic for routine checkups and 40 patients with endometrial cancer aged 55.30 +/- 6.21 years. Mutations in TP53 and BAT26 were evaluated using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and automated sequencing while serum TNF-alpha was measured using an ELISA technique. Estrogen and progesterone receptor expression in biopsy tissue was evaluated using immunohistochemical staining. RESULTS: Seven of the 40 patients (17.5%) were positive for TP53 gene alterations in exon 6, while 9 patients (22.5%) were positive for TP53 alterations in exon 7. Cases positive for TP53 mutations had higher tumor stages. Ten patients (25%) showed MSI in BAT26. Nearly all patients with mutations in BAT26 had a strong family history for endometrial cancer (chi2=13.33, p<0.05). There was no positive correlation between the presence of MSI in the BAT26 gene and mutations in the TP53 gene or high serum TNF-alpha levels. Cases positive for TP53 mutations had a significantly higher level of TNF-alpha than cases negative for TP53 mutations (p<0.05). Cases showing mutations in exon 6 or 7 of TP53 showed a significantly higher intensity of immunohistochemical staining for estrogen and progesterone receptor expression in biopsy tissue than cases negative for mutations. (chi2=8.11, p<0.05). CONCLUSION: Our results suggest that the development of endometrial carcinoma is probably mediated through a multi-step carcinogenesis pathway and mutation of TP53 does not necessarily result from the presence of microsatellite instability in BAT26. The high serum TNF-alpha levels detected in our patients may represent an immunological antitumor response that was particularly evident in cases positive for TP53 mutations.