Secondary Logo

Institutional members access full text with Ovid®

Evaluation of Cyclin D1 as a Discriminatory Immunohistochemical Biomarker for Idiopathic Pulmonary Fibrosis

Wei, Christina H., MD; Baratelli, Felicita E., MD; Xiao, Guang-Qian, MD, PhD; Koss, Michael N., MD; Elatre, Wafaa, MD, MPH

Applied Immunohistochemistry & Molecular Morphology: February 2019 - Volume 27 - Issue 2 - p e11–e15
doi: 10.1097/PAI.0000000000000692
Online Articles: Research Articles

Background: Distinction of idiopathic pulmonary fibrosis (IPF) from other chronic fibrosing interstitial pneumonitides, such as hypersensitivity pneumonitis (HP) and connective tissue diseases, is critical due to varied biological and clinical outcomes. However, their histologic overlaps often pose diagnostic challenges. A recent study suggested an association of herpesvirus saimiri infection with IPF. Productive viral infection is associated with coexpression of pirated mammalian protein cyclin D1, shown to be overexpressed by immunohistochemistry (IHC) in the regenerating alveolar epithelium in IPF but not in normal lungs. We evaluated the diagnostic utility of cyclin D1 to discriminate between IPF and other fibrosing interstitial lung diseases.

Materials and Methods: A retrospective study of cyclin D1 IHC expression in 27 consecutive cases of chronic fibrosing interstitial lung diseases from 2011 to 2017: 12 usual interstitial pneumonia (UIP) pattern; 5 nonspecific interstitial pneumonia pattern; 3 HP pattern; 7 unclassifiable was performed. Five cases of normal lung obtained from lobectomy specimen for malignancy are included as control. Immunoreactivity was graded semiquantitatively on a scale of 0 to 3.

Results: Cyclin D1 staining was uniformly strongly positive in all cases evaluated in the study, particularly in proliferating type II pneumocytes in the region of fibrosing areas. There was no statistical difference in the extent of cyclin D1 expression between UIP and non-UIP groups (2.7 vs. 2.5) and IPF versus non-IPF groups (2.7 vs. 2.4). Cyclin D1 expression is lower in control group compared with UIP groups (1.2 vs. 2.7).

Conclusions: Cyclin D1 is not a specific marker of UIP pattern/IPF. The high expression of cyclin D1 in lung tissue of fibrosing interstitial pneumonitides regardless of etiology most likely correlates with proliferation in type II pneumocytes.

Department of Pathology, Keck Medical Center, University of Southern California, Los Angeles, CA

The authors declare no conflict of interest.

Reprints: Michael N. Koss, MD, Department of Pathology, Keck Medical Center, University of Southern California, HC4 1450 San Pablo Street, Los Angeles, CA 90033 (e-mail:

Received February 1, 2018

Accepted June 24, 2018

Copyright 2019 Wolters Kluwer Health, Inc. All rights reserved.