title: Immunohistochemical evaluation of pulmonary lymphangioleiomyomatosis.
abstract: BACKGROUND
  Lymphangioleiomyomatosis (LAM) is a rare interstitial lung disease characterized by abnormal smooth muscle-like cell (LAM cell) proliferation in the lung stroma. The origin of LAM cells is still unknown. The gold-standard immunohistochemical diagnostic for LAM is an immunopositive reaction to the HMB-45 antibody.
  
  
  METHODS
  We aimed to evaluate 15 diagnostic open-lung biopsy specimens of pulmonary LAM. Based on the LAM histologic score (LHS), we distinguished two groups of histological severity: early- and advanced-stage LAM. The expression of HMB-45, estrogen receptor (ER), progesterone receptor (PR), β-catenin, E-cadherin, podoplanin (D2-40), mini-chromosome maintenance protein 3 (MCM3), and epidermal growth factor receptor (EGFR) was evaluated immunohistochemically. Fluorescence in situ hybridization (FISH) was performed in order to investigate amplification of the EGFR gene in LAM cells.
  
  
  RESULTS
  The expression of ER and EGFR was significantly higher in advanced than in early-stage LAM. Amplification of the EGFR gene was not detected in any of the 15 studied cases. There was a strong-positive correlation between the expression of PR, ER, β-catenin, E-cadherin, and the standard marker of LAM, HMB45.
  
  
  CONCLUSIONS
  We conclude that together with LHS, ER may be considered a useful tool for evaluating the progression of LAM. β-Catenin and E-cadherin seem to be new potential specific markers of LAM cells. The increased expression of EGFR in LAM cells is not associated with EGFR gene amplification, although it may be a marker of disease progression; the role of this receptor in LAM pathogenesis should be further investigated. Positive reaction of LAM cells with podoplain demonstrates the existence of an additional lymphatic endothelial lineage in LAM cells.
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland irminagrzegorek@o2.pl.
authors.forename: Irmina
authors.initials: I
authors.lastname: Grzegorek
authors.affiliation: Institute of Pathology, Charité Medical University, Berlin, Germany.
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.affiliation: Department of Surgery, Fourth Military Hospital, Wroclaw, Poland Department of Clinical Proceedings, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Chabowski
authors.affiliation: Department of Surgery, Fourth Military Hospital, Wroclaw, Poland Department of Clinical Proceedings, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Janczak
authors.affiliation: Department of Pathology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szolkowska
authors.affiliation: Department of Pathology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Langfort
authors.affiliation: Department of Internal Medicine, Fourth Military Hospital, Wroclaw, Poland Department of Angiology, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szuba
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegiel
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001706:Biopsy; D015820:Cadherins / Q000096:biosynthesis; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D018192:Lymphangioleiomyomatosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000096:biosynthesis; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D008562:Membrane Glycoproteins; D051176:beta Catenin; C506487:ESR1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin; C512478:EGFR protein, human
keywords: E-cadherin; EGFR; Lymphangioleiomyomatosis; podoplanin; β-catenin