J Pathol Transl Med.  2018 Nov;52(6):357-362. 10.4132/jptm.2018.09.13.

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma

Affiliations
  • 1Department of Pathology, Seoul National University Hospital, Seoul, Korea.
  • 2Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 3Department of Pathology, Hallym University Sacred Heart Hospital, Anyang, Korea.
  • 4Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea. npol181@snu.ac.kr
  • 5Department of Biostatics, Seoul National University Boramae Hospital, Seoul, Korea.

Abstract

BACKGROUND
The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma.
METHODS
Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed.
RESULTS
A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS.
CONCLUSIONS
Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.

Keyword

Adipophilin; Lung adenocarcinoma; Hypoxia; Prognosis

MeSH Terms

Adenocarcinoma*
Anoxia
Carbonic Anhydrases
Disease-Free Survival
HSP27 Heat-Shock Proteins
Humans
Lipid Metabolism
Lung*
Male
Prognosis
Up-Regulation
Carbonic Anhydrases
HSP27 Heat-Shock Proteins

Figure

  • Fig. 1. Immunohistochemical staining pattern of Adipophilin in adenocarcinoma. (A) Subnuclear basal staining pattern in acinar type adenocarcinoma. (B) Pancytoplasmic pattern in solid type adenocarcinoma.

  • Fig. 2. Expression of hypoxic signaling proteins in lung adenocarcinoma. Strong cytoplasmic positivity of heat shock protein 27 (A) and carbonic anhydrase IX (B) is found. Nuclear expression of hypoxia-inducible factor 1α is only focally present (C).

  • Fig. 3. Adipophilin expression according to predominant subtype of adenocarcinoma.

  • Fig. 4. Results of univariable survival analysis represented by Kaplan-Meier plots according to protein expression. Expression of adipophilin is significantly associated with worse progression-free survival (PFS) (A) but is not related to overall survival (OS) (B). Heat shock protein 27 shows poor prognostic impacts in both PFS (C) and OS (D).


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