Diagnostic significance of intracellular lipid droplets in grading cutaneous melanocytic tumor

• Project/Area Number: 17K15650
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Wakayama Medical University
• Principal Investigator: Fujmoto Masakazu 和歌山県立医科大学, 医学部, 助教 (90573676)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 悪性黒色腫 / 脂肪滴 / アディポフィリン / Melanoma / Adipophilin / mRNA ISH / Tissue microarray / Lipid droplet

Outline of Final Research Achievements

We found that high adipophilin (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.

Academic Significance and Societal Importance of the Research Achievements

皮膚悪性黒色腫のパラフィン切片上で免疫組織化学的にアディポフィリン(ADP)蛋白が高発現している患者の予後は不良である事が分かった。ADPの免疫染色, mRNA in situ hybridization, Ki67 index には正の相関がある事が分かった。皮膚悪性黒色腫の培養細胞におけるADPの発現と細胞の増殖率には正の相関がある事が分かった。以上の結果より、ADPが皮膚悪性黒色腫の増殖において重要な役割を果たしている可能性が示され、新しい治療標的となる可能性が示唆された。

Research Products

• [Journal Article] Adipophilin Expression in Cutaneous Malignant Melanoma Is Associated With High Proliferation and Poor Clinical Prognosis (2020)
  • Author(s): Masakazu Fujimoto, Ibu Matsuzaki, Kazuchika Nishitsuji, Yuki Yamamoto, Daisuke Murakami, Takanori Yoshikawa, Ayaka Fukui, Yuuki Mori, Masaru Nishino, Yuichi Takahashi, Yoshifumi Iwahashi, Kenji Warigaya, Fumiyoshi Kojima, Masatoshi Jinnin, Shin-Ichi Murata
  • Journal Title: Laboratory investigation Volume: 100 Issue: 5 Pages: 727-737
  • DOI: 10.1038/s41374-019-0358-y
• [Presentation] Adipophilin Expression in Cutaneous Malignant Melanoma is Associated with High Proliferation and Poor Clinical Prognosis (2020)
  • Author(s): Masakazu Fujimoto, Ibu Matsuzaki, Kazuchika Nishitsuji, Fumiyoshi Kojima, Shin-ichi Murata
  • Organizer: USCAP
  • Int'l Joint Research