Immunohistochemical expression profiles of solute carrier transporters in alpha‐fetoprotein‐producing gastric cancer

Aims Alpha‐fetoprotein ( AFP )‐producing gastric cancer ( GC ) is an aggressive tumour with high rates of liver metastasis and poor prognosis, and for which a validated chemotherapy regimen has not been established. Drug uptake by solute carrier ( SLC ) transporters is proposed as one of the mechanisms involved in sensitivity to chemotherapy. In this study, we aimed to develop important insights into effective chemotherapeutic regimens for AFP ‐producing GC . Methods and results We evaluated immunohistochemically the expression levels of a panel of SLC transporters in 20 AFP ‐producing GC s and 130 conventional GC s. SLC transporters examined were human equilibrative nucleoside transporter 1 ( hENT 1), organic anion transporter 2 ( OAT 2), organic cation transporter ( OCT ) 2, OCT 6 and organic anion‐transporting polypeptide 1B3 ( OATP 1B3). The rates of high expression levels of hENT 1 ( hENT 1 high ) and OAT 2 ( OAT 2 high ) were statistically higher in AFP ‐producing GC , compared with conventional GC . When analysing hENT 1 and OAT 2 in combination, hENT 1 high / OAT 2 high was the most particular expression profile for AFP ‐producing GC , with a greater significance than hENT 1 or OAT 2 alone. However, no significant differences in OCT 2, OCT 6 or OATP 1B3 levels were detected between AFP ‐producing and conventional GC s. However, immunoreactivity for hENT 1, OAT 2 and OCT 6 tended to be increased in GC tissues compared with non‐neoplastic epithelia. Conclusions Because hENT 1 and OAT 2 are crucial for the uptake of gemcitabine and 5‐fluorouracil, respectively, our results suggest that patients with AFP ‐producing GC could potentially benefit from gemcitabine/fluoropyrimidine combination chemotherapy. Increased expression of hENT 1, OAT 2 and OCT 6 may also be associated with the progression of GC.