title: Adipophilin expression in lung adenocarcinoma is associated with apocrine-like features and poor clinical prognosis: an immunohistochemical study of 328 cases.
abstract: OBJECTIVE
  The lipogenic pathway is up-regulated in proliferating cells. However, the clinical impact of neoplastic steatogenesis in lung cancer is unclear. The aim of the present study was to evaluate the association of intracytoplasmic lipids with the clinicopathological features of lung adenocarcinoma (ADC), by immunohistochemical analysis of adipophilin (ADP), a coating protein found on intracytoplasmic lipid droplets.
  
  
  RESULTS
  Tissue microarrays consisting of 328 primary lung ADCs surgically resected at Kyoto University Hospital were immunostained for ADP. Subsequently, correlations between ADP expression and clinical, molecular and survival data were performed. Fifty-one (15.5%) cases were ADP-positive. The presence of vascular invasion (P = 0.003), predominantly solid histology (P < 0.001), poorly differentiated type (P < 0.001), wild-type EGFR (P = 0.002), ALK fusion (P < 0.001), strong/diffuse mitochondrial staining (P < 0.001), a lack of surfactant protein B expression (P = 0.014) and a high Ki67 index (P < 0.001) were significantly correlated with ADP-positive ADC. In contrast, there were no correlations between ADP-positive ADC and sex, age, smoking history, tumour stage, thyroid transcription factor-1 expression, or KRAS mutational status. ADP-positive ADCs had apocrine-like features (P < 0.001). Patients with ADP-positive ADC had worse disease-free and overall survival (P = 0.047 and P = 0.013, respectively) than those with ADP-negative ADC.
  
  
  CONCLUSIONS
  ADP was expressed in a small proportion of lung ADCs. ADP-positive lung ADC was significantly associated with apocrine-like features, wild-type EGFR, and poor prognosis, suggesting that ADP-positive lung ADC could be a distinct subtype of lung adenocarcinoma, induced by up-regulation of the lipogenic pathway.
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.|Department of Diagnostic Pathology, Wakayama Medical University Hospital, Wakayama, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshizawa
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.|Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Sumiyoshi
authors.affiliation: Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sonobe
authors.affiliation: Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Menju
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Momose
authors.affiliation: Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000070780:Perilipin-2 / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000602982:PLIN2 protein, human; D000070780:Perilipin-2
keywords: adipophilin; apocrine-like features; lipogenic pathway; lung adenocarcinoma; prognosis