Identification of Glypican-3 as a Novel Tumor Marker for Melanoma

• Published in: Clinical cancer research Vol. 10; no. 19; pp. 6612 - 6621
• Main Authors: NAKATSURA, Tetsuya, KAGESHITA, Toshiro, ITO, Shosuke, WAKAMATSU, Kazumasa, MONJI, Mikio, IKUTA, Yoshiaki, SENJU, Satoru, ONO, Tomomichi, NISHIMURA, Yasuharu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2004
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Glypicans; Heparan Sulfate Proteoglycans - analysis; Heparan Sulfate Proteoglycans - blood; Heparan Sulfate Proteoglycans - genetics; Humans; Immunohistochemistry; Male; Medical sciences; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mice; Middle Aged; Neoplasm Staging; NIH 3T3 Cells; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumors; Tumoral marker; Malignant melanoma; Malignant tumor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0348

Purpose: We reported recently the novel tumor marker glypican-3 (GPC3) for hepatocellular carcinoma. In the present study, we investigated the expression of GPC3 in human melanoma cell lines and tissues and asked whether GPC3 could be a novel tumor marker for melanoma. Experimental Design: Expression of GPC3 mRNA and protein was investigated in human melanoma cell lines and tissues using reverse transcription-PCR and immunohistochemical analysis. Secreted GPC3 protein was quantified using ELISA in culture supernatants of melanoma cell lines and in sera from 91 patients with melanoma and 28 disease-free patients after surgical removal of primary melanoma. All of the subjects were Japanese nationals. Results: In >80% of melanoma and melanocytic nevus, there was evident expression of GPC3 mRNA and protein. Furthermore, GPC3 protein was evidenced in sera of 39.6% (36 of 91) of melanoma patients but not in sera from subjects with large congenital melanocytic nevus (0 of 5) and from healthy donors (0 of 60). Twenty-seven of 36 serum GPC3-positive patients were negative for both serum 5-S-cysteinyldopa and melanoma-inhibitory activity, well-known tumor markers for melanoma. The positive rate of serum GPC3 (39.6%) was significantly higher than that of 5-S-cysteinyldopa (26.7%) and of melanoma-inhibitory activity (20.9%). Surprisingly, we detected serum GPC3 even in patients with stage 0 in situ melanoma. The positive rate of serum GPC3 at stage 0, I, and II (44.4%, 40.0%, and 47.6%) was significantly higher than that of 5-S-cysteinyldopa (0.0%, 8.0%, and 10.0%). Also observed was the disappearance of GPC3 protein in sera from 11 patients after surgical removal of the melanoma. Conclusions: GPC3 is apparently a novel tumor marker useful for the diagnosis of melanoma, especially in early stages of the disorder.