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Updated: Aug 12, 2026
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Relationship between expression of topoisomerase II isoforms and chemosensitivity in choroidal melanoma
K Satherley1, L de Souza, M H Neale
1Department of Pathology, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK.
Abstract:
Choroidal melanoma has a high mortality rate and responds poorly to existing chemotherapy, but unexpected ex vivo sensitivity of a subset of these tumours to topoisomerase II inhibitors has been noted. Since chemoresistance may be mediated by the molecular phenotype of tumours, immunohistochemistry has been used to study the expression of both isoforms of topoisomerase II (alpha and beta) in 29 choroidal melanomas for which chemosensitivity assay data for doxorubicin or mitoxantrone are also available. Of these, eight tumours were topoisomerase II beta-positive and 11 were topoisomerase II alpha-positive. Recent studies showing genetic abnormality (often monosomy of chromosome 3) in choroidal melanoma suggest that loss of immunostaining could be due to genomic loss rather than down-regulation of topoisomerase II beta in these tumours. There was no convincing excess of anthracycline resistance in the topoisomerase II beta-negative group. Addition of topoisomerase II alpha, MDR1 (11/17 positive), LRP (16/28 positive), and MRP (5/29 positive) data in multivariate analysis did not reliably predict sensitivity or resistance. Vincristine chemosensitivity showed no relation to MDR1, LRP or MRP in 18 tumours tested. While it is possible that some tumours which do express topoisomerase II beta may respond to anthracyclines, the molecular basis of resistance or sensitivity to anthracyclines or vincristine in uveal melanoma is complex and remains incompletely understood.
Insights
Chemoresistance in choroidal melanoma is complex. While some tumors express topoisomerase II beta and may respond to anthracyclines, molecular markers do not reliably predict sensitivity or resistance to chemotherapy.
Area of Science:
- Oncology
- Ophthalmology
- Molecular Biology
Background:
- Choroidal melanoma has a high mortality rate and poor response to chemotherapy.
- Chemoresistance may be linked to tumor molecular phenotype.
- Topoisomerase II inhibitors show ex vivo sensitivity in a subset of choroidal melanomas.
Purpose of the Study:
- To investigate the expression of topoisomerase II alpha and beta in choroidal melanomas.
- To correlate topoisomerase II expression with chemosensitivity data for doxorubicin and mitoxantrone.
- To explore other molecular markers (MDR1, LRP, MRP) in relation to chemotherapy resistance.
Main Methods:
- Immunohistochemistry was used to assess topoisomerase II (alpha and beta) expression in 29 choroidal melanomas.
- Chemosensitivity assay data for doxorubicin or mitoxantrone were available for these tumors.
- Multivariate analysis included data for topoisomerase II alpha, MDR1, LRP, and MRP.
Main Results:
- Eight tumors were topoisomerase II beta-positive and 11 were topoisomerase II alpha-positive.
- No clear association was found between topoisomerase II beta negativity and anthracycline resistance.
- MDR1, LRP, and MRP expression did not reliably predict sensitivity or resistance in multivariate analysis. Vincristine sensitivity also showed no relation to these markers.
Conclusions:
- The molecular basis of chemotherapy resistance or sensitivity in uveal melanoma is complex and not fully understood.
- While topoisomerase II beta expression might indicate potential response to anthracyclines, other factors are involved.
- Further research is needed to elucidate the mechanisms underlying chemotherapy response in choroidal melanoma.
