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Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas

Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas
Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas
Background Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50–80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known.
Objectives To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease.
Methods Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1.
Results Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours.
Conclusions The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.
epidermolysis bullosa, muc1, squamous cell carcinoma, vaccine
0007-0963
540-545
Cooper, H.L.
80852309-f99f-4024-a4d7-71ba0342261a
Cook, I.S.
27a63af5-dbe2-4d25-8d68-bdd25bba5345
Theaker, J.M.
e24ec934-c79c-471c-8556-d38a15ac845b
Mallipeddi, R.
fb8126c0-26e2-4ebe-90c0-80cfccc3b19c
McGrath, J.
1dabdddd-65ad-4211-834d-5739a3081ce9
Friedmann, P.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd
Cooper, H.L.
80852309-f99f-4024-a4d7-71ba0342261a
Cook, I.S.
27a63af5-dbe2-4d25-8d68-bdd25bba5345
Theaker, J.M.
e24ec934-c79c-471c-8556-d38a15ac845b
Mallipeddi, R.
fb8126c0-26e2-4ebe-90c0-80cfccc3b19c
McGrath, J.
1dabdddd-65ad-4211-834d-5739a3081ce9
Friedmann, P.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd

Cooper, H.L., Cook, I.S., Theaker, J.M., Mallipeddi, R., McGrath, J., Friedmann, P. and Healy, E. (2004) Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas. British Journal of Dermatology, 151 (3), 540-545. (doi:10.1111/j.1365-2133.2004.06075.x).

Record type: Article

Abstract

Background Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50–80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known.
Objectives To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease.
Methods Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1.
Results Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours.
Conclusions The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.

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More information

Published date: 2004
Additional Information: Cutaneous Biology
Keywords: epidermolysis bullosa, muc1, squamous cell carcinoma, vaccine

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Local EPrints ID: 27004
URI: http://eprints.soton.ac.uk/id/eprint/27004
ISSN: 0007-0963
PURE UUID: efbfc38e-f00d-4f24-aff0-8ff2c0a0e9c4

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Date deposited: 26 Apr 2006
Last modified: 15 Mar 2024 07:14

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Contributors

Author: H.L. Cooper
Author: I.S. Cook
Author: J.M. Theaker
Author: R. Mallipeddi
Author: J. McGrath
Author: P. Friedmann
Author: E. Healy

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