This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bosserhoff, A.-K. Articles by Buettner, R. Search for Related Content PubMed PubMed Citation Articles by Bosserhoff, A.-K. Articles by Buettner, R.

Melanoma-inhibiting Activity, a Novel Serum Marker for Progression of Malignant Melanoma¹

Departments of Pathology [A-K. B., R. B.], Dermatology [A-K. B. W. S.], and Surgery [H. Z.], University of Regensburg Medical School, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg; Boehringer Mannheim, Werk Tutzing, Bahnhofstrasse 9-15, D-82324 Tutzing [M. K.]; Boehringer Mannheim, Werk Penzberg, Am Nonnenwald 2, D-82372 Penzberg [B. K., I. B.]; and Department of Dermatology and Allergology, Technical University of Munich, Am Biederstein, D-80802 Munich [R. H.], Germany

Melanoma-inhibiting activity (MIA) was isolated previously as a small soluble protein secreted from malignant melanoma cell lines in vitro. In vivo, highly restricted expression patterns in melanocytic tumors were identified. We therefore quantitated serum levels of MIA protein by means of a nonradioactive ELISa and investigated whether MIA provides a clinically useful parameter in patients with malignant melanomas. Here, we report enhanced MIA serum levels in 13 and 23% of patients with stage I and II disease, respectively, and in 100% with stage III or IV disease. Compared with S-100 and soluble intercellular adhesion molecule 1 serum levels in these patients, MIA was the most sensitive marker. Response to therapy in stage IV disease correlated with changes in MIA serum levels. Measuring repeatedly sera of 350 patients with a history of stage I or II melanoma during follow-up, we detected 32 patients developing positive MIA values. At the time of serum analysis, 15 of them had developed metastases, and one presented with metastatic disease 6 months later. In contrast, none of the patients with normal MIA serum levels developed metastases during the follow-up period of 6–12 months. In conclusion, MIA represents a novel serum marker for systemic malignant melanoma revealing the highest sensitivity and specificity among currently available markers. Useful clinical applications include staging of primary melanomas, detection of progression from localized to metastatic disease during follow-up, and monitoring therapy of advanced melanomas.

¹ This work was supported by grants from the Deutsche Forschungsgemeinschaft and the Krebshilfe (to R. B. and R. H.) and by Boehringer Mannheim.

² To whom requests for reprints should be addressed. Phone: (49) 941-944 6627; Fax: (49) 941-944 6602.

Received 4/10/97. Accepted 6/11/97.

This article has been cited by other articles:

				R. Bauer, M. Humphries, R. Fassler, A. Winklmeier, S. E. Craig, and A.-K. Bosserhoff Regulation of Integrin Activity by MIA J. Biol. Chem., April 28, 2006; 281(17): 11669 - 11677. [Abstract] [Full Text] [PDF]

				S. S. Kadkol, A. Y. Lin, V. Barak, I. Kalickman, L. Leach, K. Valyi-Nagy, D. Majumdar, S. Setty, A. J. Maniotis, R. Folberg, et al. Osteopontin expression and serum levels in metastatic uveal melanoma: a pilot study. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 802 - 806. [Abstract] [Full Text] [PDF]

				G. C. Cesana, G. DeRaffele, S. Cohen, D. Moroziewicz, J. Mitcham, J. Stoutenburg, K. Cheung, C. Hesdorffer, S. Kim-Schulze, and H. L. Kaufman Characterization of CD4+CD25+ Regulatory T Cells in Patients Treated With High-Dose Interleukin-2 for Metastatic Melanoma or Renal Cell Carcinoma J. Clin. Oncol., March 1, 2006; 24(7): 1169 - 1177. [Abstract] [Full Text] [PDF]

				H. Schmidt, J. S. Johansen, P. Sjoegren, I. J. Christensen, B. S. Sorensen, K. Fode, J. Larsen, and H. von der Maase Serum YKL-40 Predicts Relapse-Free and Overall Survival in Patients With American Joint Committee on Cancer Stage I and II Melanoma J. Clin. Oncol., February 10, 2006; 24(5): 798 - 804. [Abstract] [Full Text] [PDF]

				Y. Ikuta, T. Nakatsura, T. Kageshita, S. Fukushima, S. Ito, K. Wakamatsu, H. Baba, and Y. Nishimura Highly Sensitive Detection of Melanoma at an Early Stage Based on the Increased Serum Secreted Protein Acidic and Rich in Cysteine and Glypican-3 Levels Clin. Cancer Res., November 15, 2005; 11(22): 8079 - 8088. [Abstract] [Full Text] [PDF]

				S. Mian, S. Ugurel, E. Parkinson, I. Schlenzka, I. Dryden, L. Lancashire, G. Ball, C. Creaser, R. Rees, and D. Schadendorf Serum Proteomic Fingerprinting Discriminates Between Clinical Stages and Predicts Disease Progression in Melanoma Patients J. Clin. Oncol., August 1, 2005; 23(22): 5088 - 5093. [Abstract] [Full Text] [PDF]

				C. Voit, M. Kron, J. Rademaker, M. Schwurzer-Voit, W. Sterry, L. Weber, C. Ozdemir, T. Proebstle, and U. Keilholz Molecular Staging in Stage II and III Melanoma Patients and Its Effect on Long-Term Survival J. Clin. Oncol., February 20, 2005; 23(6): 1218 - 1227. [Abstract] [Full Text] [PDF]

				T. Nakatsura, T. Kageshita, S. Ito, K. Wakamatsu, M. Monji, Y. Ikuta, S. Senju, T. Ono, and Y. Nishimura Identification of Glypican-3 as a Novel Tumor Marker for Melanoma Clin. Cancer Res., October 1, 2004; 10(19): 6612 - 6621. [Abstract] [Full Text] [PDF]

				M. B. Faries, R. K. Gupta, X. Ye, E. C. Hsueh, and D. L. Morton Melanoma-Inhibiting Activity Assay Predicts Survival in Patients Receiving a Therapeutic Cancer Vaccine After Complete Resection of American Joint Committee on Cancer Stage III Melanoma Ann. Surg. Oncol., January 1, 2004; 11(1): 85 - 93. [Abstract] [Full Text] [PDF]

				I. Poser, M. Golob, R. Buettner, and A. K. Bosserhoff Upregulation of HMG1 Leads to Melanoma Inhibitory Activity Expression in Malignant Melanoma Cells and Contributes to Their Malignancy Phenotype Mol. Cell. Biol., April 15, 2003; 23(8): 2991 - 2998. [Abstract] [Full Text] [PDF]

				R. Stoll, C. Renner, R. Buettner, W. Voelter, A.-K. Bosserhoff, and T. A. Holak Backbone dynamics of the human MIA protein studied by 15N NMR relaxation: Implications for extended interactions of SH3 domains Protein Sci., March 1, 2003; 12(3): 510 - 519. [Abstract] [Full Text] [PDF]

				I. Poser, M. Golob, M. Weidner, R. Buettner, and A. K. Bosserhoff Down-Regulation of COOH-Terminal Binding Protein Expression in Malignant Melanomas Leads to Induction of MIA Expression Cancer Res., October 15, 2002; 62(20): 5962 - 5966. [Abstract] [Full Text] [PDF]

				M. Moser, A.-K. Bosserhoff, E. B. Hunziker, L. Sandell, R. Fassler, and R. Buettner Ultrastructural Cartilage Abnormalities in MIA/CD-RAP-Deficient Mice Mol. Cell. Biol., March 1, 2002; 22(5): 1438 - 1445. [Abstract] [Full Text] [PDF]

				M. Deichmann, A. Benner, M. Bock, A. Jackel, K. Uhl, V. Waldmann, and H. Naher S100-Beta, Melanoma-Inhibiting Activity, and Lactate Dehydrogenase Discriminate Progressive From Nonprogressive American Joint Committee on Cancer Stage IV Melanoma J. Clin. Oncol., June 1, 1999; 17(6): 1891 - 1891. [Abstract] [Full Text] [PDF]

				M. Muhlbauer, N. Langenbach, W. Stolz, R. Hein, M. Landthaler, R. Buettner, and A.-K. Bosserhoff Detection of Melanoma Cells in the Blood of Melanoma Patients by Melanoma-inhibitory Activity (MIA) Reverse Transcription-PCR Clin. Cancer Res., May 1, 1999; 5(5): 1099 - 1105. [Abstract] [Full Text] [PDF]

				J. C. Lougheed, J. M. Holton, T. Alber, J. F. Bazan, and T. M. Handel Structure of melanoma inhibitory activity protein, a member of a recently identified family of secreted proteins PNAS, May 8, 2001; 98(10): 5515 - 5520. [Abstract] [Full Text] [PDF]