title: Overexpression of CD90 (Thy-1) in pancreatic adenocarcinoma present in the tumor microenvironment.
abstract: CD90 (Thy-1) plays important roles in oncogenesis and shows potential as a candidate marker for cancer stem cells (CSCs) in various malignancies. Herein, we investigated the expression of CD90 in pancreatic adenocarcinoma (PDAC), with a comparison to normal pancreas and non-malignant pancreatic disease, by immunohistochemical (IHC) analysis of tissue microarrays containing 183 clinical tissue specimens. Statistical analysis was performed to evaluate the correlation between CD90 expression and the major clinicopathological factors after adjustment of age and gender. The IHC data showed that CD90 was significantly overexpressed in PDAC and its metastatic cancers as compared to chronic pancreatitis and benign islet tumors, while it was negative in normal pancreas and 82.7% of adjacent normal pancreas tissues. The abundant CD90 expression was predominantly present in PDAC stroma, such as fibroblasts and vascular endothelial cells, which could serve as a promising marker to distinguish pancreatic adenocarcinoma from normal pancreas and non-malignant pancreatic diseases. Double immunostaining of CD90 with CD24, a CSC marker for PDAC, showed that there was little overlap between these two markers. However, CD90+ fibroblast cells were clustered around CD24+ malignant ducts, suggesting that CD90 may be involved in the tumor-stroma interactions and promote pancreatic cancer development. Furthermore, CD90 mostly overlapped with α-smooth muscle actin (αSMA, a marker of activated pancreatic stellate cells (PSCs)) in PDAC stroma, which demonstrated that CD90+ stromal cells consist largely of activated PSCs. Double immunostaining of CD90 and a vascular endothelial cell marker CD31 demonstrated that CD90 expression on vascular endothelial cells was significantly increased in PDACs as compared to normal pancreas and non-malignant pancreatic diseases. Our findings suggest that CD90 could serve as a promising marker for pancreatic adenocarcinoma where desmoplastic stroma plays an important role in tumor growth and angiogenesis.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States of America.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States of America; Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Smathorn
authors.initials: S
authors.lastname: Thakolwiboon
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States of America; Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Lubman
mesh_terms: D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism*; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015703:Antigens, CD; D018800:Thy-1 Antigens