Prognostic impact of HNF4α expression in interstitial lung disease.

Publisher: Published by Blackwell Scientific Publications for the Japanese Society of Pathology Country of Publication: Australia NLM ID: 9431380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1827 (Electronic) Linking ISSN: 13205463 NLM ISO Abbreviation: Pathol Int Subsets: MEDLINE

Original Publication: Carlton South, Vic., Australia : Published by Blackwell Scientific Publications for the Japanese Society of Pathology, c1994-

Lung Diseases, Interstitial*/diagnosis ; Lung Diseases, Interstitial*/pathology ; Prognosis*; Hepatocyte Nuclear Factor 4/*metabolism; Aged ; Alveolar Epithelial Cells/metabolism ; Alveolar Epithelial Cells/pathology ; Biomarkers/metabolism ; Disease Progression ; Female ; Humans ; Idiopathic Pulmonary Fibrosis/diagnosis ; Idiopathic Pulmonary Fibrosis/pathology ; Lung/pathology ; Male ; Middle Aged ; Survival Rate

Pneumocyte injury is a crucial factor influencing the severity of interstitial lung disease (ILD). In this study, we investigated the potential of hepatocyte nuclear factor α (HNF4α) as an immunohistochemical marker to detect pneumocyte injury and as a prognostic marker. Surgical lung biopsy specimens were collected from 309 patients with different types of ILDs (61 idiopathic pulmonary fibrosis (IPF), 173 non-IPF, and 75 unclassifiable ILD). HNF4α expression were examined and the frequency of positive cells (per mm ² ) was calculated. HNF4α was strongly expressed in regenerating pneumocytes present on fibroblastic foci, Masson bodies/organizing alveoli. In the non-IPF and unclassifiable ILD groups, cases with high frequency expression showed significantly poorer outcome. Particularly, in the unclassifiable ILD group, the prognostic impact was more significant (death due to ILD, log-rank test, p < 0.0001), with a 10-year survival rate (hazard ratio 11.1, Wald test, p = 0.0003), as compared to the non-IPF group (log-rank test, p = 0.0269; hazard ratio 2.7, Wald test, p = 0.0334). Multivariable analysis focusing on the unclassifiable ILD group confirmed that the frequent HNF4α expression was an independent prognostic factor (hazard ratio 28.6; Wald test, p = 0.0033). Thus, HNF4α can be utilized as an immunohistochemical marker for pneumocyte injury and have prognostic impact particularly in unclassifiable ILD.
(© 2021 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

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18K07020 JSPS KAKENHI; 17K08724 JSPS KAKENHI; Smoking Research Foundation

Keywords: HNF4α; interstitial lung disease; prognosis

0 (Biomarkers)
0 (Hepatocyte Nuclear Factor 4)

Date Created: 20211013 Date Completed: 20220308 Latest Revision: 20220308

20240628

10.1111/pin.13176

34643024