ABSTRACT
CONTEXT: Desmoid tumors arising in the lung and pleura are extremely rare and can resemble other, more common neoplasms native to these sites. Alterations of the adenomatous polyposis coli/beta-catenin pathway have been detected in sporadic desmoid tumors and have been associated with nuclear accumulation of beta-catenin and overexpression of cyclin D1. OBJECTIVE: To analyze the expression of beta-catenin and cyclin D1 in desmoid tumors and solitary fibrous tumors (SFTs), and to compare the utilities of these substances for distinguishing between these entities with those of other, more commonly used stains. DESIGN: Formalin-fixed, paraffin-embedded sections of 4 desmoid tumors (1 pulmonary, 1 pleural, 2 pleural/chest wall), and 5 benign and 6 malignant SFTs of the pleura were immunostained for beta-catenin, cyclin D1, ALK1, CD34, vimentin, desmin, smooth muscle actin, muscle-specific actin, S100, and pancytokeratin. Staining intensity and the percentage of stained tumor cells were assessed semiquantitatively. RESULTS: Diffuse moderate or strong nuclear staining for beta-catenin was found in all desmoid tumors, 4 of 5 benign SFTs, and 2 of 6 malignant SFTs. All cases except 1 benign SFT showed concurrent cytoplasmic staining. Nuclear and cytoplasmic cyclin D1 staining was increased in all groups. The best distinction between desmoid tumors and SFTs was provided by CD34 (desmoid tumors, 0/4; SFTs, 8/11) and smooth muscle actin (desmoid tumors, 4/4; SFTs, 0/11). CONCLUSIONS: Our findings suggest that alterations in the adenomatous polyposis coli/beta-catenin pathway and cyclin D1 dysregulation may contribute to the pathogenesis of pleuropulmonary desmoid tumors and SFTs. CD34 and smooth muscle actin stains are particularly useful for differentiating between pleuropulmonary desmoid tumors and SFTs.
Subject(s)
Cyclin D1/metabolism , Leiomyoma/metabolism , Lung Neoplasms/metabolism , Pleural Neoplasms/metabolism , beta Catenin/metabolism , Actins/metabolism , Adult , Aged , Antigens, CD34/metabolism , Cell Nucleus/metabolism , Child, Preschool , Cytoplasm/metabolism , Diagnosis, Differential , Female , Fibromatosis, Aggressive , Humans , Immunohistochemistry , Male , Middle Aged , Muscle, Smooth/metabolism , Staining and LabelingABSTRACT
BACKGROUND: This study was designed to investigate abnormalities in gene expression in ductal adenocarcinoma of the pancreas using cDNA arrays. METHODS: Gene expression in pancreatic ductal adenocarcinoma was compared with normal pancreatic tissue controls. Specimens from 5 patients with pancreatic adenocarcinoma were taken fresh at operation and analyzed using commercially prepared cDNA arrays evaluating approximately 2,000 genes. Immunohistochemical staining was used to confirm protein expression of selected genes. RESULTS: Alpha-1-antitrypsin (A1AT) and glutathione S-transferase pi (GSTP) were significantly up-regulated in all 5 tumors. Vascular endothelial growth factor (VEGF) was up-regulated in 4 of the 5 patients. Immunohistochemical staining verified the overexpression of each of these genes. CONCLUSIONS: A1AT, GSTP, and VEGF are overexpressed in human pancreatic adenocarcinoma specimens taken fresh at operation. To our knowledge, this is the first study of human pancreatic ductal adenocarcinoma demonstrating the up-regulation of these genes using gene expression arrays.