Connie G Glasgow1, Gustavo Pacheco-Rodriguez1, Wendy K Steagall1, Mary E Haughey2, Patricia A Julien-Williams1, Mario P Stylianou3, Bernadette R Gochuico4, Joel Moss5. 1. Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. 2. Office of the Clinical Director, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. 3. Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. 4. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. 5. Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Electronic address: mossj@nhlbi.nih.gov.
Abstract
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women caused by proliferation of neoplastic-like LAM cells, with mutations in the TSC1/2 tumor suppressor genes. Based on case reports, levels of cancer antigen 125 (CA-125), an ovarian cancer biomarker, can be elevated in patients with LAM. We hypothesized that elevated serum CA-125 levels seen in some patients with LAM were due to LAM, not other malignancies, and might respond to sirolimus treatment. METHODS: Serum CA-125 levels were measured for 241 patients at each visit. Medical records were reviewed for co-morbidities, disease progression, and response to sirolimus treatment. CA-125 expression in LAM cells was determined by using immunohistochemical analysis. RESULTS: Almost 25% of patients with LAM had at least one elevated serum CA-125 measurement. Higher serum CA-125 levels correlated with lower FEV1, premenopausal status, and pleural effusion in a multivariate model (each P < .001). Serum CA-125 levels decreased following sirolimus treatment (P = .002). CA-125 and α-smooth muscle actin were co-expressed in LAM lung nodules. CONCLUSIONS: Higher serum CA-125 levels were associated with pleural effusions and reduced pulmonary function and were decreased with sirolimus therapy. LAM cells express CA-125. Some elevated serum CA-125 levels may reflect serosal membrane involvement.
BACKGROUND:Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women caused by proliferation of neoplastic-like LAM cells, with mutations in the TSC1/2tumor suppressor genes. Based on case reports, levels of cancer antigen 125 (CA-125), an ovarian cancer biomarker, can be elevated in patients with LAM. We hypothesized that elevated serum CA-125 levels seen in some patients with LAM were due to LAM, not other malignancies, and might respond to sirolimus treatment. METHODS: Serum CA-125 levels were measured for 241 patients at each visit. Medical records were reviewed for co-morbidities, disease progression, and response to sirolimus treatment. CA-125 expression in LAM cells was determined by using immunohistochemical analysis. RESULTS: Almost 25% of patients with LAM had at least one elevated serum CA-125 measurement. Higher serum CA-125 levels correlated with lower FEV1, premenopausal status, and pleural effusion in a multivariate model (each P < .001). Serum CA-125 levels decreased following sirolimus treatment (P = .002). CA-125 and α-smooth muscle actin were co-expressed in LAM lung nodules. CONCLUSIONS: Higher serum CA-125 levels were associated with pleural effusions and reduced pulmonary function and were decreased with sirolimus therapy. LAM cells express CA-125. Some elevated serum CA-125 levels may reflect serosal membrane involvement.
Authors: Jing Tang; Li-Juan Zhang; Min Kang; Rong Huang; Hui-Ye Shu; Hong Wei; Jie Zou; Yi-Cong Pan; Qian Ling; Yi Shao Journal: Front Genet Date: 2022-09-19 Impact factor: 4.772