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Metallothionein - overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients.

Weinlich G, Eisendle K, Hassler E, Baltaci M, Fritsch PO, Zelger B - Br. J. Cancer (2006)

Bottom Line: In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis.The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis.Similarly, Kaplan-Meier curves gave highly significant disadvantages for the MT-positive group.

View Article: PubMed Central - PubMed

Affiliation: Clinical Department of Dermatology and Venerology, Innsbruck Medical University, Anichstrasse 35, Innsbruck A-6020, Austria. georg.weinlich@uibk.ac.at

ABSTRACT
Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel-Haenszel chi2 test, Kaplan-Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (P<0.0001). Similarly, Kaplan-Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2-10.2; P<0.0001 for progression; relative risk 7.1; 95% CI 4.7-10.9; P<0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma.

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Kaplan–Meier estimates for progression and survival in melanoma patients.
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fig2: Kaplan–Meier estimates for progression and survival in melanoma patients.

Mentions: Figure 2 illustrates the progression and survival of melanoma patients over a time period of 150 months estimated by the Kaplan–Meier method. A total of 55.9% of the MT-positive group, but only 10.9% of the MT-negative group developed metastasis after 10 years of observation (P<0.0001); 44.1% of MT-positive patients died within a period of 120 months due to progression of melanoma, but only 6.8% of patients in the MT-negative group (P<0.0001). According to the tumour node metastasis (TNM) classification of the American Joint Committee on Cancer 2001, we subdivided our patients into four groups (<1.0 mm, 1.01–2.0 mm, 2.01–4.0 mm, >4.01 mm) with similar results. Even in the group of low-risk melanomas thinner than 1.0 mm, the prognosis for the MT-positive group was worse in comparison with the MT-negative group. Figure 3 illustrates the Kaplan–Meier curves for the progress-free interval; analogous data for survival are not shown.


Metallothionein - overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients.

Weinlich G, Eisendle K, Hassler E, Baltaci M, Fritsch PO, Zelger B - Br. J. Cancer (2006)

Kaplan–Meier estimates for progression and survival in melanoma patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361379&req=5

fig2: Kaplan–Meier estimates for progression and survival in melanoma patients.
Mentions: Figure 2 illustrates the progression and survival of melanoma patients over a time period of 150 months estimated by the Kaplan–Meier method. A total of 55.9% of the MT-positive group, but only 10.9% of the MT-negative group developed metastasis after 10 years of observation (P<0.0001); 44.1% of MT-positive patients died within a period of 120 months due to progression of melanoma, but only 6.8% of patients in the MT-negative group (P<0.0001). According to the tumour node metastasis (TNM) classification of the American Joint Committee on Cancer 2001, we subdivided our patients into four groups (<1.0 mm, 1.01–2.0 mm, 2.01–4.0 mm, >4.01 mm) with similar results. Even in the group of low-risk melanomas thinner than 1.0 mm, the prognosis for the MT-positive group was worse in comparison with the MT-negative group. Figure 3 illustrates the Kaplan–Meier curves for the progress-free interval; analogous data for survival are not shown.

Bottom Line: In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis.The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis.Similarly, Kaplan-Meier curves gave highly significant disadvantages for the MT-positive group.

View Article: PubMed Central - PubMed

Affiliation: Clinical Department of Dermatology and Venerology, Innsbruck Medical University, Anichstrasse 35, Innsbruck A-6020, Austria. georg.weinlich@uibk.ac.at

ABSTRACT
Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel-Haenszel chi2 test, Kaplan-Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (P<0.0001). Similarly, Kaplan-Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2-10.2; P<0.0001 for progression; relative risk 7.1; 95% CI 4.7-10.9; P<0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma.

Show MeSH
Related in: MedlinePlus