Epstein-Barr virus is absent in gastric superficial neoplastic lesions.

Epstein-Barr virus (EBV) has been associated with about 9% of all gastric carcinomas, but its role in gastric carcinogenesis remains unclear since there is lack of evidence of EBV presence in pre-neoplastic lesions of gastric mucosa. This study intends to determine the prevalence of EBV in gastric dysplasia and superficial neoplasia to clarify whether EBV infection is an early or late event in gastric cancer development. This retrospective study included a total of 242 gastric lesions from 199 consecutive patients who were referred for endoscopic resection. The histological classification of lesions includes 137 low- and high-grade dysplasia and 105 superficial carcinomas. EBV infection was investigated by EBER-ISH. Results showed that EBV was not detected in any epithelial cells of any case with dysplasia or superficial carcinomas, although we observed the presence of a small number of EBV-infected lymphocytes in 2.1% of all lesions. These results showed that EBV is not present in gastric dysplasia neither in superficial carcinomas suggesting that EBV carcinogenesis is a late event in well/moderately differentiated gastric carcinogenesis.

Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal.

AIM: To determine the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS: We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer (GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. EBV was detected by in situ hybridization for the detection of EBV-encoded small RNAs (EBERs) and EBV latent proteins (LMP1 and LMP2A) were detected by immunohistochemistry. RESULTS: The analysis showed that EBV-associated gastric carcinomas (EBVaGC) represents 8.4% (15/179) of all GC cases, with a significant differential distribution among histological types (P < 0.001): 100% (3/3) of medullary carcinomas, 100% (1/1) of adenosquamous carcinoma, 8.7% (8/92) of tubular adenocarcinomas, 8.0% (2/25) of mixed carcinomas and 2% (1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of EBVaGC in the upper third and middle (cardia, fundus and body) of the stomach (P = 0.041), a significant lower number of regional lymph nodes invasion (P = 0.025) and a tendency for better prognosis (P = 0.222). EBV latent protein expression revealed that all EBVaGC cases were LMP1-negative, nevertheless 6 cases (40%) expressed LPM2A, which reveals that these cases show a distinct EBV-Latency profile (latency II-like). CONCLUSION: EBVaGC represents 8.4% of all GC in the North Region of Portugal. The EBV-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.

P53 deregulation in Epstein-Barr virus-associated gastric cancer.

TP53 is a tumour suppressor gene frequently mutated in human cancers; nevertheless, in EBV-associated malignancies mutations are uncommon despite frequent deregulation of the p53 pathway. In this study, we aimed to investigate p53 expression, TP53 mRNA levels and TP53 mutations in EBV-associated gastric carcinoma (EBVaGC). A case-control study was performed using 46 patients: 15 EBVaGC and 31 EBV-negative GC (EBVnGC) cases. p53 expression was detected by immunohistochemistry (IHC), the evaluation of p53 mRNA levels was performed by RT-qPCR and TP53 mutations were investigated only in EBVaGC cases using the DNA sanger sequencing method. p53 expression was found in 97.8% (45/46) of all gastric cancer cases (including EBVaGC and EBVnGC groups). Despite the high frequency of p53 expression in both groups, the percentages of cells are significantly higher among EBVaGC cases (p = 0.027). Regarding the mRNA levels, we found a significantly increased expression of p53 mRNA in EBVnGC (2-ΔΔCt = 13.4 ± 2.4; p = 0.0029) when compared with EBVaGC. Furthermore, the sequencing analysis of TP53 gene revealed that only one of the 15 EBVaGC cases presented a missense mutation. Our results demonstrated that EBV-associated gastric carcinomas are characterized by a significant decrease of TP53 mRNA levels with a strong p53 expression and rare TP53 mutations when compared with EBV-negative cancers. Considering these results, EBV seems to induce a stabilization of p53 in the EBVaGC independently of the presence of mutations, which remains to be explained.

Epstein-Barr virus gene expression and latency pattern in gastric carcinomas: a systematic review.

METHODS: A systematic review of literature was conducted to identify all published reports regarding the expression of Epstein-Barr Virus (EBV) proteins/transcripts and EBV latency patterns in EBV-associated gastric carcinomas (EBVaGC). RESULTS: The literature search retrieved 247 papers, of which 25 papers matched the inclusion criteria. The analysis reveals that the most frequently expressed EBV latent proteins are EBNA1 (98.1%) and LMP2A (53.8%), while LMP1 and LMP2B are present in only 10% of cases. Lytic proteins, such as BARF0 and BARF1, and other lytic transcripts are present in almost half of cases. CONCLUSION: EBVaGC seems to display a unique transcription/latency pattern that does not fit the 'standard' EBV latency patterns and therefore should be further studied to better understand EBVaGC carcinogenesis.

Let-7c is a Candidate Biomarker for Cervical Intraepithelial Lesions: A Pilot Study.

BACKGROUND: Numerous studies have been performed to discover predictive/prognostic biomarkers for human papillomavirus (HPV) infection and cervical cancer development. More recently, microRNAs were suggested as possible biomarkers of HPV-associated cancers and our aim was to characterize the expression of let-7c in exfoliated cervical cells from women with cervical intraepithelial lesions. METHODS: Let-7c expression was evaluated by quantitative reverse transcription-polymerase chain reaction in 73 women with normal or cervical intraepithelial lesions: normal epithelium with (n = 17) and without (n = 21) HPV infection; low-grade squamous intraepithelial lesions (n = 14); and high-grade squamous intraepithelial lesions (n = 21). RESULTS: Data showed a trend to down-regulation in women with low-grade squamous intraepithelial lesions (2(-ΔΔCt) = 0.38, p = 0.06) and a significant decreased expression of let-7c in women with low-grade squamous intraepithelial lesions (2(-ΔΔCt) = 0.21; p = 0.004). The combined analysis of all cervical intraepithelial lesions revealed a down-regulation of let-7c expression (2(-ΔΔCt) = 0.27; p = 0.011). CONCLUSION: Our results showed that let-7c expression is significantly changed in the different cervical intraepithelial lesions and its levels should be further investigated as a possible biomarker for cervical intraepithelial lesions using exfoliated cervical cells as the sample source.