Nuclear HER3 is associated with favorable overall survival in uveal melanoma†
Eric Trocmé
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
E.T., D.M. and C.C.J. contributed equally to this work
Search for more papers by this authorDimitrios Mougiakakos
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
E.T., D.M. and C.C.J. contributed equally to this work
Search for more papers by this authorC. Christian Johansson
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
E.T., D.M. and C.C.J. contributed equally to this work
Search for more papers by this authorCharlotta All-Eriksson
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
Search for more papers by this authorMario A. Economou
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Olle Larsson
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Olle Larsson, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 70366
Yingbo Lin, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 75242,
Search for more papers by this authorStefan Seregard
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
Search for more papers by this authorRolf Kiessling
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Yingbo Lin
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Olle Larsson, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 70366
Yingbo Lin, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 75242,
Search for more papers by this authorEric Trocmé
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
E.T., D.M. and C.C.J. contributed equally to this work
Search for more papers by this authorDimitrios Mougiakakos
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
E.T., D.M. and C.C.J. contributed equally to this work
Search for more papers by this authorC. Christian Johansson
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
E.T., D.M. and C.C.J. contributed equally to this work
Search for more papers by this authorCharlotta All-Eriksson
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
Search for more papers by this authorMario A. Economou
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Olle Larsson
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Olle Larsson, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 70366
Yingbo Lin, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 75242,
Search for more papers by this authorStefan Seregard
Ophthalmic Pathology and Oncology Service, St Erik's Eye Hospital, Stockholm, Sweden
Search for more papers by this authorRolf Kiessling
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Yingbo Lin
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
Olle Larsson, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 70366
Yingbo Lin, CCK R8:04, Karolinska Hospital, SE-17176 Stockholm, Sweden, Tel.: +46 8 517 75242,
Search for more papers by this authorAbstract
HER3 is a member of the epidermal growth factor receptor (EGFR) family and is expressed in several types of cancer. Both the cytoplasmic and nuclear appearances of the receptor have been reported. Here, we investigate the expression and subcellular distribution of HER3 in uveal melanoma (UM) cells and tissues and its potential impact on clinical outcome of patients. Paraffin-embedded samples from 128 consecutive UM patients, enucleated without alternative treatment on UM diagnosis, were evaluated for HER3 using immunohistochemistry. Immunoreactivity was scored for frequency, intensity of positive cells, and subcellular distribution. The results were correlated with the established clinicopathological parameters using univariate and multivariate statistical analyses. HER3 expression was shown in 70% of the cases (89/128). This contrasts with the other EGFR family receptors (EGFR, HER2 and HER4) that are infrequently expressed in UM. Surprisingly, HER3 was found to be localized solely in the cell nuclei in 56 cases. The remaining 33 HER3 positive cases showed diffuse distribution (cytoplasmic ± nuclear). Nuclear HER3 was independently correlated with a more favorable overall survival (p = 0.043 and hazard ratio = 0.618) compared to cases with diffuse and/or no HER3. Nuclear localization of HER3 was also confirmed in fresh UM material and in UM cell lines. In conclusion, HER3 is frequently localized solely in the cell nuclei in UM and as such it predicts a more favorable overall survival.
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