ABSTRACT
BACKGROUND: Ghrelin is an orexigenic gut peptide produced predominantly by the stomach. Gastric mucosal ghrelin production could be compromised by an infiltrating adenocarcinoma. AIMS: To assess the expression of ghrelin mRNA and peptide in oesophagogastric adenocarcinomas and adjacent non-neoplastic mucosa. METHODS: 10 gastric and 22 oesophageal adenocarcinoma archival samples were randomly selected from a database. The presence of ghrelin-positive cells was assessed in cancer and corresponding non-neoplastic mucosa by immunohistochemistry. Quantitative reverse transcriptase polymerase chain reaction (PCR) for ghrelin mRNA was also performed on 24 gastric and 8 oesophageal adenocarcinoma specimens and adjacent non-neoplastic mucosa. RESULTS: Immunohistochemistry and reverse transcriptase PCR confirm a negligible expression of ghrelin in adenocarcinoma specimens. By contrast, non-neoplastic gastric mucosa was rich in ghrelin-positive cells and ghrelin mRNA. The number (median and range) of ghrelin-positive cells per 2 mm section of non-neoplastic mucosa was 73 (45-215) in the corpus; this was significantly higher than in cardia mucosa (9 (0-64), p<0.001) and antral mucosa (5 (0-14), p<0.001). CONCLUSIONS: Gastric and oesophageal adenocarcinomas have no ghrelin-producing cells. The highest level of ghrelin expression was noted in the non-neoplastic mucosa of the gastric corpus. Disruption of the gastric ghrelin-producing mechanism may occur during oesophagogastric malignancy.
Subject(s)
Adenocarcinoma/metabolism , Esophageal Neoplasms/metabolism , Peptide Hormones/biosynthesis , Stomach Neoplasms/metabolism , Gastric Mucosa/metabolism , Ghrelin , Humans , Immunoenzyme Techniques , Neurosecretory Systems/metabolism , Peptide Hormones/genetics , RNA, Messenger/genetics , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction/methodsABSTRACT
BACKGROUND AND OBJECTIVES: The enzyme telomerase is re-activated in most cancers but its mechanism of regulation in oesophageal carcinogenesis is unclear. The aim of this study was to determine the roles of human telomerase reverse transcriptase (hTERT) mRNA expression and hTERT mRNA splicing in the regulation of telomerase enzyme activity in Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: Paired samples from oesophageal adenocarcinoma (n=21) and adjacent macroscopically normal mucosa, and paired samples from Barrett's oesophagus (n=16) and adjacent cardia mucosa were obtained. Telomerase activity was measured by the telomeric repeat amplification protocol assay. hTERT mRNA was quantified using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Splice variants within the hTERT reverse transcriptase domain (alpha, beta, alpha beta) were detected by RT-PCR. RESULTS: In oesophageal adenocarcinoma, compared to adjacent mucosa, median telomerase activity increased significantly (from 5 to 229 total product generated (tpg), P=0.0002), but median hTERT mRNA levels were not significantly different. Similarly, median telomerase activity was significantly higher in oesophageal adenocarcinoma compared to Barrett's oesophagus (229 vs 20 tpg, P=0.001), but hTERT mRNA levels were not significantly different. There was no significant difference in telomerase activity and hTERT mRNA levels between Barrett's oesophagus and adjacent cardia. The frequency of detection of all variants increased from cardia to Barrett's oesophagus to oesophageal adenocarcinoma (P<0.05). CONCLUSIONS: A major increase in telomerase activity occurs after the Barrett's oesophagus stage in oesophageal carcinogenesis. Levels of hTERT mRNA and hTERT mRNA splicing patterns did not correlate with telomerase activity and do not appear to regulate enzyme activity. In this cancer, an important clinical diagnostic role for the transcripts of the telomerase gene is improbable.
