Importance of MutL homologue MLH1 and MutS homologue MSH2 expression in Turkish patients with sporadic colorectal cancer

AIM： To assess the incidence of MLH1 （the human MutL homologue） and MSH2 （the human MutS homologue） protein expression in Turkish patients with sporadic colorectal cancers and to compare their survival and clinicopathological features. METHODS： We validated the tissue microarray technology in 77 colorectal carcinomas by analyzing the immunohistochemical expression of proteins involved in two main pathways of colorectal carcinogenesis： p53 protein for loss of heterozygosity tumors; MLH1 and MSH2 proteins for microsatellite instability （MSI）. RESULTS： Our analysis showed that 29 （39.2%） had loss of MLH1 expression, 5 （6.8%） had loss of MSH2 expression and 2 cases had loss of expression of both proteins. We found that 60% of MSH2-negative tumors were located in the right side of the colon; all MSH2-negative cases were women. In addition, the loss of MSH2 expression was correlated with low p53 expression. Neither MLH1 nor MSH2 expressions were associated with prognosis, although there seemed a tendency of longer survival （71.7 ± 8.65 mo vs 47.08± 5.26 too） for the patients with MLHl-negative versus MLHl-positive carcinomas. There were not significant differences in overall and recurrence-free survival among MLH1/MSH2-positive and -negative cases.CONCLUSION： Our data supports that Turkish patients with MLH1- and MSH2-defective tumors have some distinct features from each other. Although prognostic importance remains controversial, immunohistochemical analysis of mismatch repair genes may be used as a routine histopathological examination of sporadic colorectal carcinomas.

Analysis of serum antibody profile against H pylori VacA and CagA antigens in Turkish patients with duodenal ulcer

AIM: To investigate the frequency of seropositivity aga- inst CagA, VacA proteins and to determine their indepen- dent effects on the development of duodenal ulcer (DU) in Turkish patients. METHODS: The study was designed as a prospective one from a tertiary referral hospital. Dyspeptic patients who were referred to our endoscopy unit for upper gas- trointestinal endoscopy between June 2003 and March 2004 and diagnosed to have DU or nonulcer dyspepsia (NUD) were included. Biopsies from the antrum and body of the stomach were taken in order to assess the current H pylori status by histology, rapid urease test and culture. Fasting sera were obtained from all patients and H pylori status of all sera was determined by IgG antibo- dies using an enzyme-linked immunosorbent assay (ELI- SA) kit. All seropositive patients were further analysed using Western blot assays detecting IgG antibodies aga- inst CagA and VacA proteins. The χ2 test was used for statistical comparison of the values and age-sex adjusted multiple regression analysis was used to determine the independent effects of CagA and VacA seropositivities on the development of DU. RESULTS: Sixty-three patients with DU and 62 patients with NUD were eligible for the final analysis. Seropositi- vity for anti-CagA was detected in 51 of 62 (82%), andin 55 of 63 (87%) patients with NUD and DU, respec- tively (p = no significance), and seropositivity for anti- VacA was found in 25 of 62 (40% ) and in 16 of 63 (25%) patients, with NUD and DU, respectively. CONCLUSION: These findings suggest that none of the- se virulence factors is associated with the development of DU in the studied Turkish patients with dyspepsia.

Discrepancy among microsatellite instability detection methodologies in non-colorectal cancer:Report of 3 cases

BACKGROUND Microsatellite instability(MSI)is a predictive biomarker for cancer immunotherapy.The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors.It can be assessed using next-generation sequencing(NGS),fluorescent multiplex PCR,and immunohistochemistry(IHC).CASE SUMMARY Here,we report 3 cases with discordant MSI results detected using different methods.A cholangiocellular carcinoma case revealed proficient mismatch repair(MMR)by IHC but high MSI(MSI-H)by liquid NGS.A cervical cancer case revealed deficient MMR by IHC,microsatellite stable by PCR,and MSI-H by NGS.Lastly,an endometrial cancer case revealed proficient MMR by IHC but MSI-H by NGS.CONCLUSION IHC for MMR status is the first choice due to several advantages.However,in cases of indeterminate IHC results,molecular testing by MSI-PCR is preferred.Recently,NGS-based MSI assays are being widely used to detect MSI-H tumors.All three methods have high accuracy;however,the inconsistencies between them may lead to misdiagnosis.