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Promyelocytic Leukemia Antigen Expression: a Histological Marker for Primary Biliary Cholangitis Diagnosis?
J Transl Int Med. 2021 Mar 31;9(1):43-51. doi: 10.2478/jtim-2021-0008. eCollection 2021 Mar.
Panagiotis A Papamichalis12, Kalliopi Zachou2, Roidoula A Papamichali1, Maria Ioannou1, Nikolaos K Gatselis2, George N Dalekos2, George K Koukoulis1
1Department of Pathology, Medical School, University of Thessaly, 41110 Larissa, Greece.
2Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110 Larissa, Greece.
Background and objectives: Distinguishing primary biliary cholangitis (PBC) from other cholestatic diseases at the histological level could be assisted by new methods, such as immunohistochemical staining of specific antigens.
Methods: We evaluated whether the detection of promyelocytic leukemia protein (PML) can serve as a specific and sensitive marker for PBC diagnosis. Liver biopsies from 26 PBC patients, 20 primary sclerosing cholangitis (PSC), 37 viral hepatitis, 11 non-alcoholic steatohepatitis (NASH) and 5 normal patients were investigated after immunostaining with the anti-PML monoclonal PG-M3, IgG1 antibody.
Results: Immunoreactivity in bile ducts was expressed by the PML-score (quotient of positive ducts to the total number of portal tracts multiplied by 2). PML-score was higher in PBC as compared to controls (P < 0.001). Using a cutoff of 0.18, PML-score proved highly sensitive (84.6%) and specific (89.7%) for confirming PBC as compared to only 5% of PSC, 9.1% of NASH and 13.5% of viral hepatitis patients (P < 0.001). Irrespective of the underlying disease, patients with PML-score > 0.18 were older (P = 0.007), more often females (P < 0.001) with higher ALP (P < 0.001), γ-GT (P = 0.001) and IgM (P < 0.001) compared to the patients with PML-score < 0.18.
Conclusions: We postulate that a simple PML immunohistochemical test could be sufficient for histopathological discrimination of PBC in problematic cases of undefined cholestatic disorders, including small-duct PSC and AMA-negative PBC cases.