Skip to main content
Top
Published in: Cellular Oncology 3/2012

01-06-2012 | Original Paper

MMP2 expression is a prognostic marker for primary melanoma patients

Authors: Anand Rotte, Magdalena Martinka, Gang Li

Published in: Cellular Oncology | Issue 3/2012

Login to get access

Abstract

Background

Matrix metalloproteinase 2 (MMP2) is a collagenase, which aids tumor growth and invasion by digesting the extracellular matrix surrounding the tumor tissue. Our study examined MMP2 expression in various stages of melanoma progression and tested the prognostic significance of MMP2 expression. We also analyzed the correlation between p-Akt status and MMP2 expression in melanoma patients.

Methods

Tissue microarray (TMA) and immunohistochemistry were employed to study the expression of MMP2. A total of 482 melanoma (330 primary and 152 metastatic) tumor biopsies and 149 nevi biopsies (49 normal and 100 dysplastic nevi) were used for the analysis. MMP2 expression was correlated with melanoma progression. Kaplan-Meier survival curve and multivariate Cox regression analysis were applied to verify the prognostic significance of MMP2 expression. The correlation between MMP2 and p-Akt expression was analyzed in 92 cases which were common in the present and the previous study on p-Akt expression.

Results

Strong MMP2 expression is significantly increased in primary (25 %) and metastatic melanoma (43 %) compared to normal (5 %) and dysplastic nevi (10 %). Patients with strong MMP2 had significantly poorer survival compared to those with negative-to-moderate MMP2 expression. MMP2 expression could predict the patient survival independent of tumor thickness and ulceration. Furthermore, in our cohort study MMP2 expression was associated with p-Akt status and patient survival.

Conclusions

Strong MMP2 staining is associated with worse survival of melanoma patients and is an independent molecular prognostic factor for primary melanoma.
Literature
1.
go back to reference T.L. Diepgen, V. Mahler, The epidemiology of skin cancer. Br. J. Dermatol. 146(Suppl 61), 1–6 (2002)PubMedCrossRef T.L. Diepgen, V. Mahler, The epidemiology of skin cancer. Br. J. Dermatol. 146(Suppl 61), 1–6 (2002)PubMedCrossRef
2.
go back to reference A.C. Geller, S.M. Swetter, K. Brooks, M.F. Demierre, A.L. Yaroch, Screening, early detection, and trends for melanoma: current status (2000–2006) and future directions. J. Am. Acad. Dermatol. 57(4), 555–572 (2007). quiz 573–556PubMedCrossRef A.C. Geller, S.M. Swetter, K. Brooks, M.F. Demierre, A.L. Yaroch, Screening, early detection, and trends for melanoma: current status (2000–2006) and future directions. J. Am. Acad. Dermatol. 57(4), 555–572 (2007). quiz 573–556PubMedCrossRef
5.
go back to reference M.B. Lens, T.G. Eisen, Systemic chemotherapy in the treatment of malignant melanoma. Expert. Opin. Pharmacother. 4(12), 2205–2211 (2003)PubMedCrossRef M.B. Lens, T.G. Eisen, Systemic chemotherapy in the treatment of malignant melanoma. Expert. Opin. Pharmacother. 4(12), 2205–2211 (2003)PubMedCrossRef
6.
go back to reference C.M. Balch, S.J. Soong, J.E. Gershenwald, J.F. Thompson, D.S. Reintgen, N. Cascinelli et al., Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J. Clin. Oncol. 19(16), 3622–3634 (2001)PubMed C.M. Balch, S.J. Soong, J.E. Gershenwald, J.F. Thompson, D.S. Reintgen, N. Cascinelli et al., Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J. Clin. Oncol. 19(16), 3622–3634 (2001)PubMed
7.
go back to reference A.N. Houghton, D. Polsky, Focus on melanoma. Canc. Cell. 2(4), 275–278 (2002)CrossRef A.N. Houghton, D. Polsky, Focus on melanoma. Canc. Cell. 2(4), 275–278 (2002)CrossRef
8.
go back to reference R.M. Turner, K.J. Bell, R.L. Morton, A. Hayen, A.B. Francken, K. Howard et al., Optimizing the frequency of follow-up visits for patients treated for localized primary cutaneous melanoma. J. Clin. Oncol. 29(35), 4641–4646 (2011) R.M. Turner, K.J. Bell, R.L. Morton, A. Hayen, A.B. Francken, K. Howard et al., Optimizing the frequency of follow-up visits for patients treated for localized primary cutaneous melanoma. J. Clin. Oncol. 29(35), 4641–4646 (2011)
9.
go back to reference K.Y. Bilimoria, M.V. Raval, D.J. Bentrem, J.D. Wayne, C.M. Balch, C.Y. Ko, National assessment of melanoma care using formally developed quality indicators. J. Clin. Oncol. 27(32), 5445–5451 (2009)PubMedCrossRef K.Y. Bilimoria, M.V. Raval, D.J. Bentrem, J.D. Wayne, C.M. Balch, C.Y. Ko, National assessment of melanoma care using formally developed quality indicators. J. Clin. Oncol. 27(32), 5445–5451 (2009)PubMedCrossRef
10.
go back to reference A.C. Geller, S.M. Swetter, S. Oliveria, S. Dusza, A.C. Halpern, Reducing mortality in individuals at high risk for advanced melanoma through education and screening. J. Am. Acad. Dermatol. 65(5), S87–94 (2011)PubMedCrossRef A.C. Geller, S.M. Swetter, S. Oliveria, S. Dusza, A.C. Halpern, Reducing mortality in individuals at high risk for advanced melanoma through education and screening. J. Am. Acad. Dermatol. 65(5), S87–94 (2011)PubMedCrossRef
11.
go back to reference C.M. Balch, J.E. Gershenwald, S.J. Soong, J.F. Thompson, M.B. Atkins, D.R. Byrd et al., Final version of 2009 AJCC melanoma staging and classification. J. Clin. Oncol. 27(36), 6199–6206 (2009)PubMedCrossRef C.M. Balch, J.E. Gershenwald, S.J. Soong, J.F. Thompson, M.B. Atkins, D.R. Byrd et al., Final version of 2009 AJCC melanoma staging and classification. J. Clin. Oncol. 27(36), 6199–6206 (2009)PubMedCrossRef
12.
go back to reference J.F. Thompson, S.J. Soong, C.M. Balch, J.E. Gershenwald, S. Ding, D.G. Coit et al., Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J. Clin. Oncol. 29(16), 2199–2205 (2011)PubMedCrossRef J.F. Thompson, S.J. Soong, C.M. Balch, J.E. Gershenwald, S. Ding, D.G. Coit et al., Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J. Clin. Oncol. 29(16), 2199–2205 (2011)PubMedCrossRef
13.
go back to reference M. Bjorklund, E. Koivunen, Gelatinase-mediated migration and invasion of cancer cells. Biochim. Biophys. Acta. 1755(1), 37–69 (2005)PubMed M. Bjorklund, E. Koivunen, Gelatinase-mediated migration and invasion of cancer cells. Biochim. Biophys. Acta. 1755(1), 37–69 (2005)PubMed
14.
go back to reference E.I. Deryugina, J.P. Quigley, Matrix metalloproteinases and tumor metastasis. Canc. Metastasis Rev. 25(1), 9–34 (2006)CrossRef E.I. Deryugina, J.P. Quigley, Matrix metalloproteinases and tumor metastasis. Canc. Metastasis Rev. 25(1), 9–34 (2006)CrossRef
15.
go back to reference C.E. Brinckerhoff, J.L. Rutter, U. Benbow, Interstitial collagenases as markers of tumor progression. Clin. Canc. Res. 6(12), 4823–4830 (2000) C.E. Brinckerhoff, J.L. Rutter, U. Benbow, Interstitial collagenases as markers of tumor progression. Clin. Canc. Res. 6(12), 4823–4830 (2000)
16.
go back to reference U.B. Hofmann, J.R. Westphal, G.N. Van Muijen, D.J. Ruiter, Matrix metalloproteinases in human melanoma. J. Invest. Dermatol. 115(3), 337–344 (2000)PubMedCrossRef U.B. Hofmann, J.R. Westphal, G.N. Van Muijen, D.J. Ruiter, Matrix metalloproteinases in human melanoma. J. Invest. Dermatol. 115(3), 337–344 (2000)PubMedCrossRef
17.
go back to reference U.B. Hofmann, J.R. Westphal, A.J. Zendman, J.C. Becker, D.J. Ruiter, G.N. van Muijen, Expression and activation of matrix metalloproteinase-2 (MMP-2) and its co-localization with membrane-type 1 matrix metalloproteinase (MT1-MMP) correlate with melanoma progression. J. Pathol. 191(3), 245–256 (2000)PubMedCrossRef U.B. Hofmann, J.R. Westphal, A.J. Zendman, J.C. Becker, D.J. Ruiter, G.N. van Muijen, Expression and activation of matrix metalloproteinase-2 (MMP-2) and its co-localization with membrane-type 1 matrix metalloproteinase (MT1-MMP) correlate with melanoma progression. J. Pathol. 191(3), 245–256 (2000)PubMedCrossRef
18.
go back to reference T. Turpeenniemi-Hujanen, Gelatinases (MMP-2 and −9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie. 87(3–4), 287–297 (2005)PubMedCrossRef T. Turpeenniemi-Hujanen, Gelatinases (MMP-2 and −9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie. 87(3–4), 287–297 (2005)PubMedCrossRef
19.
go back to reference A.H. Vaisanen, M. Kallioinen, T. Turpeenniemi-Hujanen, Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma. Hum. Pathol. 39(3), 377–385 (2008)PubMedCrossRef A.H. Vaisanen, M. Kallioinen, T. Turpeenniemi-Hujanen, Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma. Hum. Pathol. 39(3), 377–385 (2008)PubMedCrossRef
20.
go back to reference S. Shukla, G.T. Maclennan, D.J. Hartman, P. Fu, M.I. Resnick, S. Gupta, Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int. J. Canc. 121(7), 1424–1432 (2007)CrossRef S. Shukla, G.T. Maclennan, D.J. Hartman, P. Fu, M.I. Resnick, S. Gupta, Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int. J. Canc. 121(7), 1424–1432 (2007)CrossRef
21.
go back to reference V. Vasko, M. Saji, E. Hardy, M. Kruhlak, A. Larin, V. Savchenko et al., Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer. J. Med. Genet. 41(3), 161–170 (2004)PubMedCrossRef V. Vasko, M. Saji, E. Hardy, M. Kruhlak, A. Larin, V. Savchenko et al., Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer. J. Med. Genet. 41(3), 161–170 (2004)PubMedCrossRef
22.
go back to reference D.L. Dai, M. Martinka, G. Li, Prognostic significance of activated Akt expression in melanoma: a clinicopathologic study of 292 cases. J. Clin. Oncol. 23(7), 1473–1482 (2005)PubMedCrossRef D.L. Dai, M. Martinka, G. Li, Prognostic significance of activated Akt expression in melanoma: a clinicopathologic study of 292 cases. J. Clin. Oncol. 23(7), 1473–1482 (2005)PubMedCrossRef
23.
go back to reference K.M. Sze, K.L. Wong, G.K. Chu, J.M. Lee, T.O. Yau, I. Oi-Lin Ng, Loss of phosphatase and tensin homolog enhances cell invasion and migration through AKT/Sp-1 transcription factor/matrix metalloproteinase 2 activation in hepatocellular carcinoma and has clinicopathologic significance. Hepatology 53(5), 1558–1569 (2011)PubMedCrossRef K.M. Sze, K.L. Wong, G.K. Chu, J.M. Lee, T.O. Yau, I. Oi-Lin Ng, Loss of phosphatase and tensin homolog enhances cell invasion and migration through AKT/Sp-1 transcription factor/matrix metalloproteinase 2 activation in hepatocellular carcinoma and has clinicopathologic significance. Hepatology 53(5), 1558–1569 (2011)PubMedCrossRef
24.
go back to reference H. Lin, R.P. Wong, M. Martinka, G. Li, Loss of SNF5 expression correlates with poor patient survival in melanoma. Clin. Canc. Res. 15(20), 6404–6411 (2009)CrossRef H. Lin, R.P. Wong, M. Martinka, G. Li, Loss of SNF5 expression correlates with poor patient survival in melanoma. Clin. Canc. Res. 15(20), 6404–6411 (2009)CrossRef
25.
go back to reference W. Remmele, H.E. Stegner, Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 8(3), 138–140 (1987)PubMed W. Remmele, H.E. Stegner, Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 8(3), 138–140 (1987)PubMed
26.
go back to reference A. Vaisanen, P. Kuvaja, M. Kallioinen, T. Turpeenniemi-Hujanen, A prognostic index in skin melanoma through the combination of matrix metalloproteinase-2, Ki67, and p53. Hum. Pathol. 42(8), 1103–1111 (2011)PubMedCrossRef A. Vaisanen, P. Kuvaja, M. Kallioinen, T. Turpeenniemi-Hujanen, A prognostic index in skin melanoma through the combination of matrix metalloproteinase-2, Ki67, and p53. Hum. Pathol. 42(8), 1103–1111 (2011)PubMedCrossRef
27.
go back to reference F. Su, W.D. Bradley, Q. Wang, H. Yang, L. Xu, B. Higgins et al., Resistance to selective BRAF inhibition can be mediated by modest upstream pathway activation. Cancer Res. 72(4), 969–978 (2012)PubMedCrossRef F. Su, W.D. Bradley, Q. Wang, H. Yang, L. Xu, B. Higgins et al., Resistance to selective BRAF inhibition can be mediated by modest upstream pathway activation. Cancer Res. 72(4), 969–978 (2012)PubMedCrossRef
28.
go back to reference J.A. Sparano, P. Bernardo, P. Stephenson, W.J. Gradishar, J.N. Ingle, S. Zucker et al., Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J. Clin. Oncol. 22(23), 4683–4690 (2004)PubMedCrossRef J.A. Sparano, P. Bernardo, P. Stephenson, W.J. Gradishar, J.N. Ingle, S. Zucker et al., Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J. Clin. Oncol. 22(23), 4683–4690 (2004)PubMedCrossRef
29.
go back to reference R.L. Camp, V. Neumeister, D.L. Rimm, A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J. Clin. Oncol. 26(34), 5630–5637 (2008)PubMedCrossRef R.L. Camp, V. Neumeister, D.L. Rimm, A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J. Clin. Oncol. 26(34), 5630–5637 (2008)PubMedCrossRef
Metadata
Title
MMP2 expression is a prognostic marker for primary melanoma patients
Authors
Anand Rotte
Magdalena Martinka
Gang Li
Publication date
01-06-2012
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 3/2012
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-012-0080-x

Other articles of this Issue 3/2012

Cellular Oncology 3/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine