Sequential expression of putative stem cell markers in gastric carcinogenesis

• Published in: British journal of cancer Vol. 105; no. 5; pp. 658 - 665
• Main Authors: Wang, T, Ong, C W, Shi, J, Srivastava, S, Yan, B, Cheng, C L, Yong, W P, Chan, S L, Yeoh, K G, Iacopetta, B, Salto-Tellez, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.08.2011; Nature Publishing Group
• Subjects: 631/80/86; 692/699/67/1504/1829; 692/699/67/1857; 692/700/1750; AC133 Antigen; Adult; Aged; Aged, 80 and over; Antigens, CD - analysis; Antigens, CD - metabolism; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Pharmacological - analysis; Biomarkers, Pharmacological - metabolism; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma - diagnosis; Carcinoma - drug therapy; Carcinoma - metabolism; Carcinoma - pathology; Clinical Trials, Phase II as Topic; Drug Resistance; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Glycoproteins - analysis; Glycoproteins - metabolism; Humans; Hyaluronan Receptors - analysis; Hyaluronan Receptors - metabolism; Immunohistochemistry; Male; Medical sciences; Middle Aged; Molecular Diagnostics; Molecular Medicine; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - metabolism; Oncology; Peptides - analysis; Peptides - metabolism; Precancerous Conditions - diagnosis; Precancerous Conditions - metabolism; Predictive Value of Tests; RNA-Binding Proteins - analysis; RNA-Binding Proteins - metabolism; Stomach Neoplasms - diagnosis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Time Factors; Tumors; Musashi-1; gastric cancer; Correa pathway; CD44; CD133; Transmembrane protein; Stem cell; Cell adhesion molecule; Biological marker; Malignant tumor; Musashi-I; Stomach cancer; Carcinogenesis; Cancerology; Sequential; Digestive diseases; Cancer; Gastric disease
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.287

Background: Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers. Methods: We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression. Results: We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa ( P <0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival ( P =0.014 and P =0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy. Conclusion: CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.