Kohtaro Miyamoto, Manabu Iwadate, Yuka Yanagisawa, Emi Ito, Jun-Ichi Imai, Masaya Yamamoto, Naoki Sawada, Motonobu Saito, Satoshi Suzuki, Izumi Nakamura, Shinji Ohki, Zenichiro Saze, Michihiko Kogure, Mitsukazu Gotoh, Kazutoshi Obara, Hiromasa Ohira, Kazuhiro Tasaki, Masafumi Abe, Naoki Goshima, Shinya Watanabe, Satoshi Waguri, Seiichi Takenoshita
INTERNATIONAL JOURNAL OF ONCOLOGY 39(5) 1109-1115 2011年11月 査読有り
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract that are diagnosed by c-kit staining in most cases. A lysosomal cysteine proteinase termed cathepsin L has been commonly associated with malignancy in several cancer types, but this finding has not been reported for GISTs. We analyzed the cathepsin L mRNA and protein expression in GISTs. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that cathepsin L levels were higher in GISTs than those in gastric or colorectal tumors; this finding was supported by results of the Western blot analysis. Immunohistochemistry revealed that cathepsin L was localized to the cytoplasm of GIST cells as an intense granular signal, which was not observed in the cells of leiomyoma, a mesenchymal tumor that was analyzed as a control specimen. Double immunofluorescence microscopy revealed that a portion of the granular signal colocalized with lysosome-associated membrane protein-1 (LAMP-1.), which is a lysosomal marker. Moreover, immunohistochemical analysis of 43 tumor specimens revealed that 86.0% (n=37) were cathepsin-L positive, and this positivity was significantly correlated with c-kit positivity but not with other clinicopathological factors, including gender, age, region, size, mitosis and risk of recurrence. From these results, we conclude that cathepsin L is highly expressed in GISTs compared to its expression in other cancerous lesions; this identifies cathepsin-L as a new diagnostic marker for GISTs.