Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis

Abstract

Adipophilin (ADP) is a primary protein component of lipid droplets (LDs). For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigated the association between ADP and other pathological characteristics in cutaneous malignant melanomas to clarify the role of ADP in melanoma cells. We immunostained whole paraffin sections of primary cutaneous melanomas obtained from 90 cases for ADP, after which we analyzed the correlation between ADP immunohistochemistry (IHC) and patient survival data. We also studied the relationship between the ADP IHC score and in situ hybridization (ISH) score of ADP mRNA, and the Ki67-labeling index (Ki67-LI) by using tissue microarrays consisting of 74 primary cutaneous malignant melanomas, 19 metastasizing melanomas, and 29 melanocytic nevi. Finally, we analyzed the relationship between ADP expression and cell proliferation in cutaneous melanoma cell lines. We found that high ADP expression was associated with poor metastasis-free survival, disease-specific survival, and overall survival rates of patients with cutaneous melanomas (P < 0.05). By linear regression analysis, ADP IHC was correlated with increasing ADP mRNA ISH H-scores and Ki67-LI scores in melanocytic lesions (P < 0.01). ADP IHC and ADP ISH H-scores and Ki67-LI scores were greater in pT3–4 melanomas than in pT1–2 melanomas. In cell-based assays, cells with increased ADP expression showed higher proliferation rates compared with those of low-ADP cells. Thus, ADP expression in malignant melanoma was significantly associated with high cell proliferation and poor clinical prognosis. Our results thus indicate a significant association between ADP and melanoma progression, and we propose that ADP may be a novel marker of aggressive cutaneous melanoma with a lipogenic phenotype.