title: Cathepsin L is highly expressed in gastrointestinal stromal tumors.
abstract: 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.
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Iwadate
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Emi
authors.initials: E
authors.lastname: Ito
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Imai
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawada
authors.forename: Motonobu
authors.initials: M
authors.lastname: Saito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakamura
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohki
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Saze
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kogure
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Gotoh
authors.forename: Kappaazutoshi
authors.initials: K
authors.lastname: Omicronbara
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ohira
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tasaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
authors.forename: Naoki
authors.initials: N
authors.lastname: Goshima
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D056668:Cathepsin L / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D021381:Protein Transport; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D014408:Biomarkers, Tumor; D056668:Cathepsin L; D051907:Lysosomal Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1