lewis-x-antigen and Pulmonary-Fibrosis

Surgical specimens of 7 cases of bronchioalveolar carcinoma complicated with pulmonary fibrosis and 4 cases of simple pulmonary fibrosis were examined histopathologically and immunohistochemically. The morphology and histogenesis of adenomatous hyperplasia (AH) of alveolar epithelium and its relation to bronchioalveolar carcinoma were investigated. The AH was classified as types I and II according to their microscopic morphologic characteristics. In this group, 6 cases of type I-AH and 5 cases of type II-AH were observed. The results of anti-SA, anti-SSEA-1 and anti-CEA monoclonal antibody examinations indicate that AH is a nonspecific hyperplastic lesion of alveolar epithelium occurred during chronic pulmonary inflammatory diseases. Both type I and II AH originated from type B alveolar epithelial cells. The latter developed on the basis of the former, but with a more immature tendency and hyperplastic potential, being a pre-malignant alteration. It could be considered that certain cases of bronchioalveolar carcinoma are originated from type B alveolar epithelial cells, some of which underwent malignant change from type II alveolar hyperplasia.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Aged; Apoproteins; Carcinoembryonic Antigen; Epithelium; Female; Humans; Hyperplasia; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Precancerous Conditions; Pulmonary Alveoli; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants

Pulmonary fibrosis begins with alveolitis, which progresses to destruction of lung tissue and excess collagen deposition. This process could be the result of DNA damage and a form of apoptosis. Therefore, we hypothesized that Fas ligand (FasL), which induces apoptosis in cells expressing Fas antigen (Fas), is associated with pulmonary fibrosis. We examined frozen lung tissues from seven patients with idiopathic pulmonary fibrosis (IPF), and bronchoalveolar lavage fluid (BALF) cells from 19 patients with IPF and from 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP). We used five frozen lungs with normal lung parenchyma and BALF cells from 10 patients with solitary pulmonary nodule as controls. Reverse transcription-polymerase chain reaction (RT-PCR) showed that FasL messenger RNA (mRNA) was expressed in BALF cells from all patients with IPF and from 15 of 16 patients with CVD-IP. FasL mRNA was not detected in BALF cells except in one of 10 controls. RT in situ PCR detected FasL mRNA in inflammatory cells in BALF from patients with IPF. Immunohistochemistry detected FasL protein in infiltrating lymphocytes and granulocytes in all of seven frozen lung tissues of IPF, but in none of five control lung tissues. Additionally, the expression of Fas appeared to be upregulated in bronchiolar and alveolar epithelial cells in IPF compared with normal lung parenchyma by immunohistochemistry. We conclude that Fas and FasL were upregulated in fibrosing lung diseases and may associate with DNA damage or apoptosis of bronchiolar and alveolar epithelial cells in this disorder.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Bronchoalveolar Lavage Fluid; CD4 Antigens; CD8 Antigens; Collagen; Cryopreservation; Fas Ligand Protein; fas Receptor; Female; Humans; Immunohistochemistry; Lewis X Antigen; Lung Diseases, Interstitial; Male; Membrane Glycoproteins; Middle Aged; Pulmonary Fibrosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Serum levels of sialyl SSEA-1 antigen, a carbohydrate antigen, were measured by radioimmunoassay in 142 patients with nonmalignant lung diseases. In 20 of 41 patients with fibrosing lung disease, either idiopathic or associated with collagen disease, the serum sialyl SSEA-1 levels were abnormally elevated. In patients with other lung diseases, the serum levels were almost within normal limits, less than 38.0 units/ml. In fibrosing lung disease the serum levels ranged from 13.8 to 147.0 units/ml and were largely concurrent with the degree of disease activity. The therapeutic effects of corticosteroid, which were evaluated with clinical-radiographic-physiologic scores and survivals in the patients with elevated serum levels, were significantly lower than those of the patients with the normal range of antigen levels. An immunohistochemical study performed on autopsied lungs from five patients with fibrosing lung disease indicated that the antigen was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in the lungs. No antigen was detectable by immunostaining in normal pulmonary epithelium among five normal lungs. From these findings, it is thought that the elevated levels of serum sialyl SSEA-1 may be derived from proliferating epithelial cells that were dominant in the late stage of fibrosing lung disorders. The measurements of serum sialyl SSEA-1 in patients with fibrosing lung disease may be clinically useful in establishing the degree of disease activity that has an influence on patient prognosis and therapeutic response.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Asthma; Humans; Immunohistochemistry; Immunoradiometric Assay; Lewis X Antigen; Lung; Pneumonia; Prognosis; Pulmonary Emphysema; Pulmonary Fibrosis