Objectives: Gastric cancer is a leading cause of cancer-related deaths worldwide, and the genetic and molecular alterations underlying its pathogenesis are largely unknown. PTEN, a tyrosine phosphatase, is frequently mutated in brain and breast cancers but not in gastric cancers. In order to assess the role of PTEN in gastric carcinogenesis, we analysed the expression of PTEN in human gastric cancer and in the gastric mucosa of cancer relatives.
Methods: Gastric cancer tissues were obtained from 26 patients with gastric cancer undergoing upper-gastrointestinal endoscopy or resection for gastric cancer. Furthermore, 21 first-degree relatives of gastric cancer patients and 12 healthy individuals agreed to undergo upper-gastrointestinal endoscopy. In all cases, biopsies were taken from the antrum and corpus. PTEN expression was assessed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis and immunohistochemistry.
Results: PTEN expression was reduced or absent in 21/26 gastric cancers compared with the matched non-malignant gastric biopsy (P < 0.001). Furthermore, PTEN expression was reduced significantly in the antrum biopsy of first-degree relatives compared with healthy controls (P < 0.05).
Conclusions: Reduced expression of PTEN in gastric cancer points to another mechanism apart from PTEN mutation that may be involved in the pathogenesis of gastric cancer. The reduction of PTEN expression was also observed in first-degree relatives.