title: Evaluation of human tissue kallikrein-related peptidases 6 and 10 expression in early gastroesophageal adenocarcinoma.
abstract: Kallikreins are a family of serine proteases that are linked to malignancy of different body organs with potential clinical utility as tumor markers. In this study, we investigated kallikrein-related peptidase 6 (KLK6) and KLK10 expression in early gastroesophageal junction adenocarcinoma and Barrett esophagus (BE) with and without dysplasia. Immunohistochemistry revealed significantly increased KLK6 expression in early invasive cancer compared with dysplastic (P = .009) and nondysplastic BE (P = .0002). There was a stepwise expression increase from metaplasia to dysplasia and invasive tumors. Significantly higher KLK10 was seen in dysplastic lesions compared with metaplasia but not between dysplastic lesions and invasive cancers. KLK6 staining intensity was increased at the invasive front (P = .006), suggesting its role in tumor invasiveness. Neither KLK6 nor KLK10 was significantly associated with other prognostic markers, including depth of invasion, indicating their potential as independent biomarkers. Our results should be interpreted with caution due to limited sample size. There was a significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect. We then compared KLK6 and KLK10 messenger RNA expression between metaplastic and cancerous tissues in an independent data set of esophageal carcinoma from The Cancer Genome Atlas. KLK6 and KLK10 may be useful markers and potential therapeutic targets in gastroesophageal junction tumors.
authors: Department of Laboratory Medicine, St Michael's Hospital, Toronto, M5B 1W8, Canada; Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, M5B 1W8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A1, Canada.
authors: Andrea
authors: A
authors: Grin
authors: Department of Laboratory Medicine, St Michael's Hospital, Toronto, M5B 1W8, Canada.
authors: Sara
authors: S
authors: Samaan
authors: Department of Laboratory Medicine, St Michael's Hospital, Toronto, M5B 1W8, Canada; Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, M5B 1W8, Canada.
authors: Monika
authors: M
authors: Tripathi
authors: Department of Laboratory Medicine, St Michael's Hospital, Toronto, M5B 1W8, Canada; Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, M5B 1W8, Canada.
authors: Fabio
authors: F
authors: Rotondo
authors: Department of Laboratory Medicine, St Michael's Hospital, Toronto, M5B 1W8, Canada; Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, M5B 1W8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A1, Canada.
authors: Kalman
authors: K
authors: Kovacs
authors: Department of Community Medicine and Public Health, Menoufiya University, Menufia 32511, Egypt.
authors: Mena N
authors: MN
authors: Bassily
authors: Department of Laboratory Medicine, St Michael's Hospital, Toronto, M5B 1W8, Canada; Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, M5B 1W8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A1, Canada. Electronic address: yousefg@smh.ca.
authors: George M
authors: GM
authors: Yousef
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D004943:Esophagogastric Junction / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007610:Kallikreins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010447:Peptide Hydrolases / Q000378:metabolism*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D010447:Peptide Hydrolases; C100936:KLK10 protein, human; C103551:KLK6 protein, human; D007610:Kallikreins
keywords: Barrett esophagus; Gastric cancer; Gastroesophageal cancer; KLK10; KLK6; Kallikreins