Immunohistochemical localization of metallothionein in benign and malignant epithelial ovarian tumors

McCluggage, W. Glenn; Strand, Kathryn; Abdulkadir, AY

doi:10.1046/j.1525-1438.2002.01081.x

Cited by 15 publications

(16 citation statements)

References 28 publications

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“…The studied group was uniform: 95% of the patients were in FIGO stage III, 86% of the studied cases involved serous carcinoma, 98% of the patients were treated with cisplatin-based schemes and 2% or one patient with a carboplatin-based scheme. We confirm that the studied proteins are expressed in ovarian carcinomas [2,17]. We have found that intensity of MT expression is higher in sections from second-look procedures (after chemotherapy) and that there is no difference in expression intensity of GST-pi between sections from primary laparotomies and second-look procedures.…”

Section: Discussionsupporting

confidence: 84%

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Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients

et al. 2005

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Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients.

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Section: Discussionsupporting

confidence: 84%

“…zinc and copper), alleviation of toxic effects of cadmium and mercury or protection of cells from oxidative stress [6,11]. Numerous reports document MT presence in cells of various tumors, including ovarian cancer [3,7,17,28].…”

Section: Introductionmentioning

confidence: 99%

Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients

et al. 2005

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“…A total of four studies were identified [57]–[60]. All studies except for Tan et al reported a significant increase [59].…”

Section: Resultsmentioning

confidence: 99%

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

et al. 2014

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Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review.Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests.A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82–17.03) and ovarian tumors (OR 7.83; 1.09–56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03–0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08–2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03–2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47–2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer.Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.

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“…The relationship between MT expression and cisplatin sensitivity has been clearly demonstrated in cultured cells [137] , and there is evidence in support of this association from clinical studies. MT expression is elevated in oesophageal, ovarian, ductal mammary tumours and adenocarcinoma of the large intestine [73,[138][139][140] ; and moreover, correlations between expression and the resistant phenotype have been observed in both oesophageal [73] and urothelial [128] cancers. The ovarian cancer study indicates that increased expression of MT is associated with a poor prognosis.…”

Section: Detoxification Of Platinum Complexesmentioning

confidence: 99%

Resistance to Chemotherapy in Cancer: A Complex and Integrated Cellular Response

Mellor¹,

Callaghan²

2008

Pharmacology

151

100

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Inherent and acquired resistance pathways account for the high rate of failure in cancer chemotherapy. The mechanisms or pathways mediating resistance may be classified as pharmacokinetic (i.e. alter intratumour drug exposue) or pharmacodynamic (i.e. failure to elicit cytotoxicity). More often than not, the resistant phenotype is characterised by alterations in multiple pathways. Consequently, the pathways may act synergistically or generate a broad spectrum of resistance to anticancer drugs. There has been a great deal of systematic characterisation of drug resistance in vitro. However, translating this greater understanding into clinical efficacy has rarely been achieved. This review explores the phenomenon of drug resistance in cancer and highlights the gap between in vitro and in vivo observations. This gap presents a major obstacle in overcoming drug resistance and restoring sensitivity to chemotherapy.

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Immunohistochemical localization of metallothionein in benign and malignant epithelial ovarian tumors

Cited by 15 publications

References 28 publications

Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients

Augmented expression of metallothionein and glutathione S-transferase pi as unfavourable prognostic factors in cisplatin-treated ovarian cancer patients

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

Resistance to Chemotherapy in Cancer: A Complex and Integrated Cellular Response

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