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

Maruya S, Shirasaki T, Nagaki T, Kakehata S, Kurotaki H, Mizukami H, Shinkawa H - BMC Cancer (2009)

Bottom Line: The associations between clinicopathological factors and outcome were analyzed.Expression of topoIIalpha 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.The results of the present study suggest that topoIIalpha expression is associated with histologically aggressive subtypes and shortened survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otolaryngology, Hirosaki University School of Medicine, Hirosaki, Japan. marucell@hotmail.com

ABSTRACT

Background: Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis. Topoisomerase IIalpha (topoIIalpha), 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 topoIIalpha in various types of salivary gland tumors and its biological significance.

Methods: The protein expression of topoIIalpha 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 (> or = 10%) of topoIIalpha protein, and 16 carcinomas (30%) and all benign tumors were negative (p < 0.001). Expression of topoIIalpha 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 topoIIalpha expression is associated with histologically aggressive subtypes and shortened survival. Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIalpha-targeting therapy in patients with salivary gland carcinoma.

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Immunohistochemistry for topoIIα in salivary gland tumors. A: Pleomorphic adenoma: few positive nuclear expressions in tumor cells (×100). B: Warthin's tumor: abundant positive expression in lymphoid cells of germinal centers, not in epithelial tumor cells (×100). C: Adenoid cystic carcinoma (Grade 1): low expression in low-grade tubular components (×100). D: Adenoid cystic carcinoma (Grade 3): high nuclear expression in high-grade solid areas (×100). E: Salivary duct carcinoma: many positive cells in foci with typical comedonecrosis (×100). F: Salivary duct carcinoma: strong and diffuse expression observed in the invasive micropapillary variant (×200).
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Figure 2: Immunohistochemistry for topoIIα in salivary gland tumors. A: Pleomorphic adenoma: few positive nuclear expressions in tumor cells (×100). B: Warthin's tumor: abundant positive expression in lymphoid cells of germinal centers, not in epithelial tumor cells (×100). C: Adenoid cystic carcinoma (Grade 1): low expression in low-grade tubular components (×100). D: Adenoid cystic carcinoma (Grade 3): high nuclear expression in high-grade solid areas (×100). E: Salivary duct carcinoma: many positive cells in foci with typical comedonecrosis (×100). F: Salivary duct carcinoma: strong and diffuse expression observed in the invasive micropapillary variant (×200).

Mentions: The immunohistochemical expression of topoIIα was negative in the epithelial cells of all 20 benign tumors, including pleomorphic adenoma and Warthin's tumor (Fig. 2A and 2B), whereas positive expression of topoIIα protein (≥10%) was found in 38 of 54 malignant tumors (70%) (p < 0.001) (Table 1). In Warthin's tumors, focal immunopositivity was detected in germinal centers of lymphoid stromal cells, but not in epithelial cells (Fig. 2B). In adenoid cystic carcinoma and mucoepidermoid carcinoma, nuclear staining of topoIIα was positive in 12 cases (71%) and 4 cases (57%), respectively. In adenoid cystic carcinoma, topoIIα expression seemed to be more remarkable in solid type than tumors composed of tubular or cribriform pattern (Fig. 2C and 2D). High expression (3+) was mainly associated with high-grade malignant tumors such as salivary duct carcinoma (83%, 5/6), adenocarcinoma not otherwise specified (43%, 3/7), and carcinoma ex pleomorphic adenoma (100%, 3/3) (Table 1). In salivary duct carcinoma, the nuclear expression of topoIIα was evident in both conventional type with comedonecrosis and microinvasive variant (Fig. 2E and 2F). All malignant components of the 3 carcinomas ex pleomorphic adenomas were mainly composed of salivary duct carcinoma.


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

Maruya S, Shirasaki T, Nagaki T, Kakehata S, Kurotaki H, Mizukami H, Shinkawa H - BMC Cancer (2009)

Immunohistochemistry for topoIIα in salivary gland tumors. A: Pleomorphic adenoma: few positive nuclear expressions in tumor cells (×100). B: Warthin's tumor: abundant positive expression in lymphoid cells of germinal centers, not in epithelial tumor cells (×100). C: Adenoid cystic carcinoma (Grade 1): low expression in low-grade tubular components (×100). D: Adenoid cystic carcinoma (Grade 3): high nuclear expression in high-grade solid areas (×100). E: Salivary duct carcinoma: many positive cells in foci with typical comedonecrosis (×100). F: Salivary duct carcinoma: strong and diffuse expression observed in the invasive micropapillary variant (×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654461&req=5

Figure 2: Immunohistochemistry for topoIIα in salivary gland tumors. A: Pleomorphic adenoma: few positive nuclear expressions in tumor cells (×100). B: Warthin's tumor: abundant positive expression in lymphoid cells of germinal centers, not in epithelial tumor cells (×100). C: Adenoid cystic carcinoma (Grade 1): low expression in low-grade tubular components (×100). D: Adenoid cystic carcinoma (Grade 3): high nuclear expression in high-grade solid areas (×100). E: Salivary duct carcinoma: many positive cells in foci with typical comedonecrosis (×100). F: Salivary duct carcinoma: strong and diffuse expression observed in the invasive micropapillary variant (×200).
Mentions: The immunohistochemical expression of topoIIα was negative in the epithelial cells of all 20 benign tumors, including pleomorphic adenoma and Warthin's tumor (Fig. 2A and 2B), whereas positive expression of topoIIα protein (≥10%) was found in 38 of 54 malignant tumors (70%) (p < 0.001) (Table 1). In Warthin's tumors, focal immunopositivity was detected in germinal centers of lymphoid stromal cells, but not in epithelial cells (Fig. 2B). In adenoid cystic carcinoma and mucoepidermoid carcinoma, nuclear staining of topoIIα was positive in 12 cases (71%) and 4 cases (57%), respectively. In adenoid cystic carcinoma, topoIIα expression seemed to be more remarkable in solid type than tumors composed of tubular or cribriform pattern (Fig. 2C and 2D). High expression (3+) was mainly associated with high-grade malignant tumors such as salivary duct carcinoma (83%, 5/6), adenocarcinoma not otherwise specified (43%, 3/7), and carcinoma ex pleomorphic adenoma (100%, 3/3) (Table 1). In salivary duct carcinoma, the nuclear expression of topoIIα was evident in both conventional type with comedonecrosis and microinvasive variant (Fig. 2E and 2F). All malignant components of the 3 carcinomas ex pleomorphic adenomas were mainly composed of salivary duct carcinoma.

Bottom Line: The associations between clinicopathological factors and outcome were analyzed.Expression of topoIIalpha 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.The results of the present study suggest that topoIIalpha expression is associated with histologically aggressive subtypes and shortened survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otolaryngology, Hirosaki University School of Medicine, Hirosaki, Japan. marucell@hotmail.com

ABSTRACT

Background: Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis. Topoisomerase IIalpha (topoIIalpha), 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 topoIIalpha in various types of salivary gland tumors and its biological significance.

Methods: The protein expression of topoIIalpha 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 (> or = 10%) of topoIIalpha protein, and 16 carcinomas (30%) and all benign tumors were negative (p < 0.001). Expression of topoIIalpha 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 topoIIalpha expression is associated with histologically aggressive subtypes and shortened survival. Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIalpha-targeting therapy in patients with salivary gland carcinoma.

Show MeSH
Related in: MedlinePlus