Expression, regulation and clinical significance of bone morphogenetic protein 6 in esophageal squamous‐cell carcinoma

• Published in: International journal of cancer Vol. 83; no. 1; pp. 38 - 44
• Main Authors: Raida, Martin, Sarbia, Mario, Clement, Joachim H., Adam, Susanne, Gabbert, Helmut E., Höffken, Klaus
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 24-09-1999; Wiley-Liss
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bone Morphogenetic Protein 6; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Culture Media, Serum-Free; ErbB Receptors - metabolism; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophagus; Esophagus - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Humans; Hypopharyngeal Neoplasms - metabolism; Immunohistochemistry; Keratinocytes - metabolism; Male; Medical sciences; Middle Aged; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Survival Rate; Time Factors; Tumor Cells, Cultured; Tumors; Histological grading; Human; Squamous cell carcinoma; Prognosis; Cytokine; Esophageal disease; Malignant tumor; Esophagus; Pathology; Membrane receptor; Regulation(control); Clinical stage; Epidermal growth factor; Histopathology; Bone morphogenetic protein; Polypeptide; Digestive diseases; Growth factor; Biological receptor
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19990924)83:1<38::AID-IJC8>3.0.CO;2-B

Bone morphogenetic proteins (BMPs) are multifunctional cytokines. BMP‐6 is involved in early steps of keratinogenesis. Esophageal squamous‐cell carcinoma often shows abnormal keratinization. The aim of this study was to examine the expression and regulation of BMP‐6 in esophageal carcinoma and to determine the relationship of its expression with tumor characteristics and survival. Avidin‐biotin‐peroxidase staining was performed using paraffin‐wax‐embedded tumor specimens collected from 172 patients with esophageal squamous‐cell carcinoma, who underwent potentially curative surgery. Expression of BMP‐6 and EGF‐receptor in the esophageal‐squamous‐cell‐carcinoma cell line COLO‐680N and the hypopharyngeal‐squamous‐cell‐carcinoma cell line FaDu was assayed with specific RT‐PCR. In standard cell‐cultivation conditions, COLO‐680N and FaDu cells showed distinct expression of BMP‐6, whereas in serum‐free conditions BMP‐6 expression was hardly detectable. The addition of EGF or EGF‐related growth factors could elevate BMP‐6 mRNA content. Immunohistochemically, all 172 tumors exhibited cytoplasmic immunoreactivity for BMP‐6. The content of BMP‐6 protein was inversely correlated with tumor differentiation (p < 0.01). Univariate survival analysis revealed that 74 patients with tumors of low immunoreactivity had higher 2‐year and 5‐year survival rates (50.0%/27.7%) than 75 patients with tumors of high immunoreactive scores (33.3%/21.6%). (p < 0.05). We conclude that BMP‐6 is expressed in esophageal squamous‐cell carcinoma. EGF‐receptor activation is crucial for regulation of BMP‐6 expression. BMP‐6 protein content is correlated with the grade of tumor‐cell differentiation and may add to indications of poor prognosis. Int. J. Cancer 83:38–44, 1999. © 1999 Wiley‐Liss, Inc.