Immunohistochemical detection of RET proto-oncogene product in tumoral and nontumoral mucosae of gastric cancer.

Objective: To detect RET (REarranged during Transfection) protein by immunohistochemistry (IHC) in gastric cancer.

Study design: A total of 210 samples were employed, of which 197 specimens were from 91 surgical pieces of gastric adenocarcinoma, comprising 91 tumoral, 91 nontumoral, and 15 intramucosal dysplastic samples. Another 13 gastric mucosae were from cancer-free patients. Two RET antibodies (clones Ret01 and 3F8) were used separately for IHC.

Results: Of the nontumoral samples from gastric cancers, 28 were positive (31%) with either antibody Ret01 or 3F8. The positive stains were often located in deep pyloric glands and associated with chronic inflammation patterns (p = 0.045). RET positivity correlated with phosphorylated epidermal growth factor receptor, which had been previously tested (p = 0.021). In tumoral samples RET was positive in 7 cases with antibody Ret01 (8%) and 9 cases with 3F8 (10%). In 15 intramucosal dysplastic samples RET was detected in 6 cases with antibody Ret01 and 8 cases with 3F8. There was an accordance between the IHC using antibodies Ret01 and 3F8 in tumoral, nontumoral, and intramucosal dysplastic samples (p = 0.500, 1.000, and 0.500). The 13 samples from cancer-free patients were always negative.

Conclusion: Activation of RET proto-oncogene may be one of the molecular pathogeneses in gastric inflammatory and tumoral diseases.