Skip to main content
Top
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Differential expression of topoisomerase IIα protein in salivary gland carcinomas: histogenetic and prognostic implications

Authors: Shin-ichiro Maruya, Takashi Shirasaki, Takahiko Nagaki, Seiji Kakehata, Hidekachi Kurotaki, Hiroki Mizukami, Hideichi Shinkawa

Published in: BMC Cancer | Issue 1/2009

Login to get access

Abstract

Background

Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis. Topoisomerase IIα (topoIIα), located at chromosome 17q21-22, is considered a major mediator of cell proliferation and DNA replication. The purpose of this study was to evaluate the expression of topoIIα in various types of salivary gland tumors and its biological significance.

Methods

The protein expression of topoIIα was evaluated immunohistochemically in formalin-fixed, paraffin-embedded tissue from 54 salivary gland carcinomas and 20 benign tumors (10 pleomorphic adenomas and 10 Warthin's tumors). The primary salivary gland carcinoma specimens consisted of 17 adenoid cystic carcinomas, 7 adenocarcinomas not otherwise specified, 7 mucoepidermoid carcinomas, 6 salivary duct carcinomas, 3 acinic cell carcinomas, 3 carcinomas ex pleomorphic adenomas, 3 epithelial-myoepithelial carcinomas, 2 carcinosarcomas, 2 lymphoepithelial carcinomas, 2 myoepithelial carcinomas, 1 oncocytic carcinoma, and 1 squamous cell carcinoma. The associations between clinicopathological factors and outcome were analyzed.

Results

Of the 54 primary salivary gland carcinomas, 38 (70%) showed positive expression (≥10%) of topoIIα protein, and 16 carcinomas (30%) and all benign tumors were negative (p < 0.001). Expression of topoIIα was more frequently observed in salivary duct carcinoma, carcinoma ex pleomorphic adenoma, adenocarcinoma, and adenoid cystic carcinoma, solid type, and it was associated with advanced stage and shortened survival.

Conclusion

The results of the present study suggest that topoIIα expression is associated with histologically aggressive subtypes and shortened survival. Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIα-targeting therapy in patients with salivary gland carcinoma.
Appendix
Available only for authorised users
Literature
1.
go back to reference Spiro RH: Management of malignant tumors of the salivary glands. Oncology. 1998, 12: 671-680.PubMed Spiro RH: Management of malignant tumors of the salivary glands. Oncology. 1998, 12: 671-680.PubMed
2.
go back to reference Sternberg SS: Histopathology for pathologists. 1997, Philadelphia: Lippincott-Raven Press, 405-425. Sternberg SS: Histopathology for pathologists. 1997, Philadelphia: Lippincott-Raven Press, 405-425.
3.
go back to reference Szanto PA, Luna MA, Tortoledo ME, White RA: Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer. 1984, 15: 1062-1069. 10.1002/1097-0142(19840915)54:6<1062::AID-CNCR2820540622>3.0.CO;2-E.CrossRef Szanto PA, Luna MA, Tortoledo ME, White RA: Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer. 1984, 15: 1062-1069. 10.1002/1097-0142(19840915)54:6<1062::AID-CNCR2820540622>3.0.CO;2-E.CrossRef
4.
go back to reference Laurie SA, Licitra L: Systemic therapy in the palliative management of advanced salivary gland cancers. J Clin Oncol. 2006, 24: 2673-2678. 10.1200/JCO.2005.05.3025.CrossRefPubMed Laurie SA, Licitra L: Systemic therapy in the palliative management of advanced salivary gland cancers. J Clin Oncol. 2006, 24: 2673-2678. 10.1200/JCO.2005.05.3025.CrossRefPubMed
5.
go back to reference Wang JC: Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol. 2002, 3: 430-440. 10.1038/nrm831.CrossRefPubMed Wang JC: Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol. 2002, 3: 430-440. 10.1038/nrm831.CrossRefPubMed
6.
go back to reference Kellner U, Sehested M, Jensen PB, Gieseler F, Rudolph P: Culprit and victim-DNA topoisomerase II. Lancet Oncol. 2002, 3: 235-243. 10.1016/S1470-2045(02)00715-5.CrossRefPubMed Kellner U, Sehested M, Jensen PB, Gieseler F, Rudolph P: Culprit and victim-DNA topoisomerase II. Lancet Oncol. 2002, 3: 235-243. 10.1016/S1470-2045(02)00715-5.CrossRefPubMed
7.
go back to reference Mano MS, Rosa DD, De Azambuja E, Ismael GF, Durbecq : The 17q12-q21 amplicon: Her2 and topoisomerase-IIα and their importance to the biology of solid tumours. Cancer Treat Rev. 2007, 33: 64-77. 10.1016/j.ctrv.2006.10.001.CrossRefPubMed Mano MS, Rosa DD, De Azambuja E, Ismael GF, Durbecq : The 17q12-q21 amplicon: Her2 and topoisomerase-IIα and their importance to the biology of solid tumours. Cancer Treat Rev. 2007, 33: 64-77. 10.1016/j.ctrv.2006.10.001.CrossRefPubMed
8.
go back to reference Glisson B, Colevas AD, Haddad R, Krane J, El-Naggar A, Kies M, Costello R, Summey C, Arquette M, Langer C, Amrein PC, Posner M: HER2 expression in salivary gland carcinomas: dependence on histological subtype. Clin Cancer Res. 2004, 10: 944-946. 10.1158/1078-0432.CCR-03-0253.CrossRefPubMed Glisson B, Colevas AD, Haddad R, Krane J, El-Naggar A, Kies M, Costello R, Summey C, Arquette M, Langer C, Amrein PC, Posner M: HER2 expression in salivary gland carcinomas: dependence on histological subtype. Clin Cancer Res. 2004, 10: 944-946. 10.1158/1078-0432.CCR-03-0253.CrossRefPubMed
9.
go back to reference Di Leo A, Gancberg D, Larsimont D, Tanner M, Jarvinen T, Rouas G, Dolci S, Leroy JY, Paesmans M, Isola J, Piccart MJ: HER-2 amplification and topoisomerase IIα gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res. 2002, 8: 1107-1116.PubMed Di Leo A, Gancberg D, Larsimont D, Tanner M, Jarvinen T, Rouas G, Dolci S, Leroy JY, Paesmans M, Isola J, Piccart MJ: HER-2 amplification and topoisomerase IIα gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res. 2002, 8: 1107-1116.PubMed
10.
go back to reference Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S, Renta V, Fronda G, Preisler HD: Amplification and overexpression of topoisomerase IIα predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res. 2002, 8: 1061-1067.PubMed Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S, Renta V, Fronda G, Preisler HD: Amplification and overexpression of topoisomerase IIα predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res. 2002, 8: 1061-1067.PubMed
11.
go back to reference Cardoso F, Durbecq V, Larsimont D, Paesmans M, Leroy JY, Rouas G, Sotiriou C, Renard N, Richard N, Richard V, Piccart MJ, Di Leo A: Correlation between complete response to anthracycline-based chemotherapy and topoisomerase II-α gene amplification and protein overexpression in locally advanced/metastatic breast cancer. Int J Oncol. 2004, 24: 201-209.PubMed Cardoso F, Durbecq V, Larsimont D, Paesmans M, Leroy JY, Rouas G, Sotiriou C, Renard N, Richard N, Richard V, Piccart MJ, Di Leo A: Correlation between complete response to anthracycline-based chemotherapy and topoisomerase II-α gene amplification and protein overexpression in locally advanced/metastatic breast cancer. Int J Oncol. 2004, 24: 201-209.PubMed
12.
go back to reference Barnes L: International Academy of Pathology, World Health Organization, International Agency for Research on Cancer. Pathology and genetics of head and neck tumours. 2005, Lyon: IARC Press Barnes L: International Academy of Pathology, World Health Organization, International Agency for Research on Cancer. Pathology and genetics of head and neck tumours. 2005, Lyon: IARC Press
13.
go back to reference Kuropkat C, Rudolph P, Parwaresch R, Werner JA: Ki-Si-a prognostic marker for hypopharyngeal carcinoma with potential predictive value for response to chemotherapy. Anticancer Res. 2003, 23: 3965-3970.PubMed Kuropkat C, Rudolph P, Parwaresch R, Werner JA: Ki-Si-a prognostic marker for hypopharyngeal carcinoma with potential predictive value for response to chemotherapy. Anticancer Res. 2003, 23: 3965-3970.PubMed
14.
go back to reference Ho DM, Hsu CY, Ting LT, Chiang H: MIB-1 and DNA topoisomerase IIα could be helpful for predicting long-term survival of patients with glioblastoma. Am J Clin Pathol. 2003, 119: 715-722. 10.1309/UN4WV65UH94JEWUV.CrossRefPubMed Ho DM, Hsu CY, Ting LT, Chiang H: MIB-1 and DNA topoisomerase IIα could be helpful for predicting long-term survival of patients with glioblastoma. Am J Clin Pathol. 2003, 119: 715-722. 10.1309/UN4WV65UH94JEWUV.CrossRefPubMed
15.
go back to reference Fritz P, Cabrera CM, Dippon J, Gerteis A, Simon W, Aulitzky WE, Kuip van der H: c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study. Breast Cancer Res. 2005, 7: R374-384. 10.1186/bcr1012.CrossRefPubMedPubMedCentral Fritz P, Cabrera CM, Dippon J, Gerteis A, Simon W, Aulitzky WE, Kuip van der H: c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study. Breast Cancer Res. 2005, 7: R374-384. 10.1186/bcr1012.CrossRefPubMedPubMedCentral
16.
go back to reference Lewis JE, Olsen KD, Sebo TJ: Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001, 32: 596-604. 10.1053/hupa.2001.25000.CrossRefPubMed Lewis JE, Olsen KD, Sebo TJ: Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001, 32: 596-604. 10.1053/hupa.2001.25000.CrossRefPubMed
17.
go back to reference Tortoledo ME, Luna MA, Batsakis JG: Carcinoma ex pleomorphic adenoma and malignant mixed tumors. Histomorphologic indexes. Arch Otolaryngol. 1984, 110: 172-176.CrossRefPubMed Tortoledo ME, Luna MA, Batsakis JG: Carcinoma ex pleomorphic adenoma and malignant mixed tumors. Histomorphologic indexes. Arch Otolaryngol. 1984, 110: 172-176.CrossRefPubMed
18.
go back to reference Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S, Renta V, Fronda G, Preisler HD: Amplification and overexpression of topoisomerase IIα predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res. 2002, 8: 1061-1067.PubMed Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S, Renta V, Fronda G, Preisler HD: Amplification and overexpression of topoisomerase IIα predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res. 2002, 8: 1061-1067.PubMed
19.
go back to reference Braybrooke JP, Levitt NC, Joel S, Davis T, Madhusudan S, Turley H, Wilner S, Harris AL, Talbot DC: Pharmacokinetic study of cisplatin and infusional etoposide phosphate in advanced breast cancer with correlation of response to topoisomerase IIα expression. Clin Cancer Res. 2003, 9: 4682-4688.PubMed Braybrooke JP, Levitt NC, Joel S, Davis T, Madhusudan S, Turley H, Wilner S, Harris AL, Talbot DC: Pharmacokinetic study of cisplatin and infusional etoposide phosphate in advanced breast cancer with correlation of response to topoisomerase IIα expression. Clin Cancer Res. 2003, 9: 4682-4688.PubMed
20.
go back to reference Nguyen LH, Black MJ, Hier M, Chauvin P, Rochon L: HER2/neu and Ki-67 as prognostic indicators in mucoepidermoid carcinoma of salivary glands. J Otolaryngol. 2003, 32: 328-331. 10.2310/7070.2003.11438.CrossRefPubMed Nguyen LH, Black MJ, Hier M, Chauvin P, Rochon L: HER2/neu and Ki-67 as prognostic indicators in mucoepidermoid carcinoma of salivary glands. J Otolaryngol. 2003, 32: 328-331. 10.2310/7070.2003.11438.CrossRefPubMed
21.
go back to reference Prat A, Parera M, Reyes V, Peralta S, Cedres S, Andreu J, Huquet P, del Campo JM: Successful treatment of pulmonary metastatic salivary ductal carcinoma with trastuzumab-based therapy. Head Neck. 2007, 30: 680-683. 10.1002/hed.20714.CrossRef Prat A, Parera M, Reyes V, Peralta S, Cedres S, Andreu J, Huquet P, del Campo JM: Successful treatment of pulmonary metastatic salivary ductal carcinoma with trastuzumab-based therapy. Head Neck. 2007, 30: 680-683. 10.1002/hed.20714.CrossRef
22.
go back to reference Maruya S, Kurotaki H, Shimoyama N, Kaimori M, Shinkawa H, Yagihashi S: Expression of p16 protein and hypermethylation status of its promoter gene in adenoid cystic carcinoma of the head and neck. ORL J Otorhinolaryngol Relat Spec. 2003, 65: 26-32.CrossRefPubMed Maruya S, Kurotaki H, Shimoyama N, Kaimori M, Shinkawa H, Yagihashi S: Expression of p16 protein and hypermethylation status of its promoter gene in adenoid cystic carcinoma of the head and neck. ORL J Otorhinolaryngol Relat Spec. 2003, 65: 26-32.CrossRefPubMed
23.
go back to reference Maruya S, Kurotaki H, Wada R, Saku T, Shinkawa H, Yagihashi S: Promoter methylation and protein expression of the E-cadherin gene in the clinicopathologic assessment of adenoid cystic carcinoma. Mod Pathol. 2004, 17: 637-645. 10.1038/modpathol.3800104.CrossRefPubMed Maruya S, Kurotaki H, Wada R, Saku T, Shinkawa H, Yagihashi S: Promoter methylation and protein expression of the E-cadherin gene in the clinicopathologic assessment of adenoid cystic carcinoma. Mod Pathol. 2004, 17: 637-645. 10.1038/modpathol.3800104.CrossRefPubMed
24.
go back to reference Norberg-Spaak L, Dardick I, Ledin T: Adenoid cystic carcinoma: use of cell proliferation, BCL-2 expression, histologic grade, and clinical stage as predictors of clinical outcome. Head Neck. 2000, 22: 489-497. 10.1002/1097-0347(200008)22:5<489::AID-HED8>3.0.CO;2-X.CrossRefPubMed Norberg-Spaak L, Dardick I, Ledin T: Adenoid cystic carcinoma: use of cell proliferation, BCL-2 expression, histologic grade, and clinical stage as predictors of clinical outcome. Head Neck. 2000, 22: 489-497. 10.1002/1097-0347(200008)22:5<489::AID-HED8>3.0.CO;2-X.CrossRefPubMed
25.
go back to reference Carlinfante G, Lazzaretti M, Ferrari S, Bianchi B, Crafa P: P53, bcl-2 and Ki-67 expression in adenoid cystic carcinoma of the palate. A clinico-pathologic study of 21 cases with long-term follow-up. Pathol Res Pract. 2005, 200: 791-799. 10.1016/j.prp.2004.08.008.CrossRefPubMed Carlinfante G, Lazzaretti M, Ferrari S, Bianchi B, Crafa P: P53, bcl-2 and Ki-67 expression in adenoid cystic carcinoma of the palate. A clinico-pathologic study of 21 cases with long-term follow-up. Pathol Res Pract. 2005, 200: 791-799. 10.1016/j.prp.2004.08.008.CrossRefPubMed
26.
go back to reference Greer RO, Said S, Shroyer KR, Marileila VG, Weed SA: Overexpression of cyclin D1 and cortactin is primarily independent of gene amplification in salivary gland adenoid cystic carcinoma. Oral Oncol. 2007, 43: 735-741. 10.1016/j.oraloncology.2006.09.007.CrossRefPubMed Greer RO, Said S, Shroyer KR, Marileila VG, Weed SA: Overexpression of cyclin D1 and cortactin is primarily independent of gene amplification in salivary gland adenoid cystic carcinoma. Oral Oncol. 2007, 43: 735-741. 10.1016/j.oraloncology.2006.09.007.CrossRefPubMed
27.
go back to reference Sakurai K, Urade M, Noguchi K, Hashitani S, Takaoka K, Segawa E, Kishimoto H: Prognostic significance of cyclooxygenase-2 and DNA topoisomerase IIα expression in oral carcinoma. Head Neck. 2007, 29: 1002-1009. 10.1002/hed.20627.CrossRefPubMed Sakurai K, Urade M, Noguchi K, Hashitani S, Takaoka K, Segawa E, Kishimoto H: Prognostic significance of cyclooxygenase-2 and DNA topoisomerase IIα expression in oral carcinoma. Head Neck. 2007, 29: 1002-1009. 10.1002/hed.20627.CrossRefPubMed
Metadata
Title
Differential expression of topoisomerase IIα protein in salivary gland carcinomas: histogenetic and prognostic implications
Authors
Shin-ichiro Maruya
Takashi Shirasaki
Takahiko Nagaki
Seiji Kakehata
Hidekachi Kurotaki
Hiroki Mizukami
Hideichi Shinkawa
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-72

Other articles of this Issue 1/2009

BMC Cancer 1/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine