Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas

AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋ （H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

Traps and trumps from adjacent-to-tumor samples in gastric cancer research

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opporttmides to the discovery of cancer biomarkers and molecular targets.