Implication of K-ras and p53 in colorectal cancer carcinogenesis in Tunisian population cohort.

According to the multistep route of genetic alterations in the colorectal adenoma-carcinoma sequence, the complex K-ras/p53 mutation is one of the first alterations to occur and represent an important genetic event in colorectal cancer (CRC). An evaluation of the mutation spectra in K-ras and p53 gene was effected in 167 Tunisian patients with sporadic CRC to determine whether our populations have similar pattern of genetic alteration as in Maghrebin's population. Mutation patterns of codon 12-13 of K-ras and exon 5-8 of p53 were analyzed by immunohistochemistry and PCR-SSCP and confirmed by sequencing. Mutations in the K-ras gene were detected in 31.13 % and affect the women more than the men (p = 0.008). Immunostaining showed that expression of p21 ras was correlated with the advanced age (p = 0.004), whereas loss of signal was associated with mucinous histotype (p = 0.003). Kaplan-Meier survival curve found that patients with the K-ras mutation had a shorter survival compared with patients without mutation (p = 0.005). Alteration in p53 was seen in 17.4 % of patients and affects three hot spot codons such as 175, 245, and 248. Overexpression of p53 was seen in 34.1 % and correlated with tumor node metastasis (TNM) advanced stage (p = 0.037) and mucinous histotype (p = 0.001). A high concordance between p53 expression and alteration (p<0.005) was shown. Concomitant mutations in K-ras and p53 gene were detected in only 4 % of tumors. K-ras and p53 undergo separate pathways in colorectal tumorogenesis. Interestingly, mutations in the K-ras gene might be considered a valuable prognostic factor correlated to poor outcome. p53 gene alterations were rather low in our set, and methylation pattern of p53 is required to elucidate the molecular basis of this protein in CRC.

Relationship between expression of ras p21 oncoprotein and mutation status of the K-ras gene in sporadic colorectal cancer patients in Tunisia.

INTRODUCTION: The K-ras proto-oncogene encodes a protein (p21-ras) belonging to the family of GTP/GDP-binding proteins with GTPase activity. The activation of ras family genes plays an important role in colorectal tumorigenesis. Frequency of K-ras mutations and overexpression of the protein in colorectal cancer (CRC) vary between 14% and 50% and between 29% and 76%, respectively. AIMS: We investigated the clinicopathologic characteristics of patients with CRC and their relationship with point mutations of K-ras oncogene codons 12/13 and ras p21 expression. MATERIALS AND METHODS: K-ras codons 12 and 13 point mutations were examined by direct sequence analysis, whereas the ras p21 expression was evaluated using immunohistochemistry. RESULTS: Statistical analysis of immunohistochemical results showed that the expression of ras p21 was correlated with the advanced age of patients (P=0.0001), whereas loss of signal was associated with mucinous histotype (P=0.0001). Mutations in the K-ras gene were detected in 12 of the patients with CRC. Mutations in K-ras gene were found in 12 of 52 tumors (23.07%), and 7 mutations were G→A transitions (58.33% of all mutations), 4 were G→T transversions (33.33%), and only 1 was G→C transversion (8.33%). A total of 83.33% of the mutation occurred at codon 12 and 16.67% at codon 13. Moreover, K-ras mutations were associated with the sex of patients (P=0.017). CONCLUSIONS: Genetic K-ras alterations were rather low in the Tunisian population, but further study is necessary to unravel the molecular background of CRC.

[Ménétrier's disease and gastric carcinoma]. / Maladie de Ménétrier et cancer gastrique association ou filiation?

The authors report 4 cases of Menetrier's disease associated with gastric adenocarcinoma and one case of low-grade dysplasia. The patients (3 men and 2 women) were aged between 53 and 81 years. In three cases the diagnosis was established by histological examination of the exicised tumor; in one case it was based on microbiopsy specimen; and in another case on a gastric tissue specimen. The authors review the anatomo-clinical features of this association and raise the problem of the relationship between Menetrier's disease, dysplasia and cancer.

[CD117 contribution in the diagnosic of mesenchymal tumors of the digestive tract]. / Apport du CD117 dans le diagnostic des tumeurs conjonctives du tube digestif.

UNLABELLED: Gastrointestinal stromal tumor (GIST) is a new distinct entity defined as CDI 17 or c-kit positive mesenchymal tumors, originaling in gastrointestinal pacemaker cells known as interstitial cells of Cajal. This study evaluate the percentage of GIST previously diagnosed as mesenchymal tumors in our hospital during 11 years. METHODS: A total of 30 surgically resected gastrointestinal tumor specimens were collected from January 1990 to December 2000 in the pathology laboratory of la Rabta Jospital. Immunohistochemical studies were performed on these tumors with antibodies of CD 117, smooth muscle actin (SMA) and protein S-100. RESULTS: Among the 30 tumors, 26 (86.6%) were CD117 positive and were classified as gastrointestinal stromal tumors. Among the 26 GIST, SMA was positive in 11 tumors (42.3%), 6 tumors (23%) expressed protein S-100. The 4 tumors classified as non-GIST were leiomyomas with the following immunohistochemical characteristics: CD117-negative with strong SMA-positive and protein S100 negative status. CONCLUSIONS: The majority (86.6%) of mesenchymal gastrointestinal tumors were GIST, except for a smalls groups of smooth muscle tumors.

[Early gastric cancer--two case reports]. / Cancer superficiel de l'estomac: a propos de 2 cas.

Gastric cancer is a serious disease with a high mortality rate. Early diagnosis of the disease improves its prognosis. We report two cases of early gastric cancer and we specify the clinical, endoscopic, histologic and therapeutic aspects of the disease. This study is about two female patients, respectively, 36 and 70 years old. The diagnosis of early gastric cancer was based on pathologic examination of the resected stomach. The two patients are in remission 2 years and 6 months later, respectively. The diagnosis of early gastric cancer is often made on nonspecific symptoms. Oeso-gastro-duodenoscopy shows gastric mucosal anomalies. Pathologic examination of gastric biopsies confirm the diagnosis of adenocarcinoma. Endoscopic ultrasound is essential; it specifies the submucosal infiltration and evaluates the lymph node invasion. Surgery is the primary treatment but in some cases endoscopic mucosal resection provides good long-term results. Early diagnosis of adenocarcinoma improves the prognosis of the disease, which remains poor nowadays.