Immunohistochemical study of nonspecific interstitial pneumonia and ubiquitin-positive pneumocytes in elderly patients

Aim: The Ubiquitin (Ub)-proteasome system maintains cellular homeostasis through proteolysis, and Ub appears in the damaged cells of many organs. Nonspecific interstitial pneumonia (NSIP) in elderly patients was studied to clarify the relationship between Ub-positive cells, cellular damage, and resistance to therapy. Methods: Specimens of surgical lung biopsy with the NSIP pattern (NSIP/P) from 13 patients (mean age, 68 years old) were examined histologically and immunohistochemically. Pneumocytes examined under high-power microscopy were counted for eosinophilic inclusion bodies and Ub-positive cells. NSIP/P was histologically evaluated and cases were scored for erosion and intraluminal granulation tissue subtypes (polypoid, mural, or occluded) as lung injury markers. NSIP/P was subdivided into cellular NSIP and fibrosing NSIP according to the proportions of interstitial inflammation and fibrosis. Results: 1) Six of 13 patients with NSIP/P had Ub-positive cells (Ub+ group), and all inclusions identified by light-microscope were positive for Ub. A greater number of Ub ⁺ pneumocytes were found compared with the inclusions by light-microscope, and Ub immunostaining was useful for the detection of the inclusions. 2) Granulation tissue scores in the Ub ⁺ group were significantly greater than in the Ub-group (p<0.05); there was no difference in granulation tissue subtypes between the groups. 3) Granulation tissue scores in fibrosing NSIP/P (including each subtype) were significantly greater than in cellular NSIP/P. 4) After a follow-up period, there was no correlation between Ub+ group and NSIP therapy resistance or between the granulation tissue subtypes and therapy resistance. Conclusion: Some elderly patients with NSIP had inclusions, and these inclusions were Ub ⁺. Pneumocyte injury might occur via the Ub-proteasome system pathway in elderly patients with NSIP/P, although there was no correlation between Ub ⁺ pneumocytes and therapy resistance.