Author:
Maruyama Satoshi,Cheng Jun,Shingaki Susumu,Tamura Takashi,Asakawa Shuichi,Minoshima Shinsei,Shimizu Yoshiko,Shimizu Nobuyoshi,Saku Takashi
Abstract
Abstract
Background
Among the salivary gland carcinomas, carcinoma in pleomorphic adenoma has been regarded as a representative carcinoma type which arises secondarily in the background of a pre-existent benign pleomorphic adenoma. It is still poorly understood how and which benign pleomorphic adenoma cells transform into its malignant form, carcinoma ex pleomorphic adenoma.
Methods
We have established five cell systems from a benign pleomorphic adenoma of the parotid gland of a 61-year-old woman. They were characterized by immunofluorescence, classical cytogenetics, p53 gene mutational analysis, fluorescence in-situ hybridization, and histopathological and immunohistochemical examinations of their xenografts, to demonstrate their potency of secondary transformation.
Results
We established and characterized five cell systems (designated as SM-AP1 to SM-AP5) from a benign pleomorphic adenoma of the parotid gland. SM-AP1 to SM-AP3 showed polygonal cell shapes while SM-AP4 and SM-AP5 were spindle-shaped. SM-AP1-3 cells were immunopositive for keratin only, indicating their duct-epithelial or squamous cell differentiation, while SM-AP4/5 cells were positive for both keratin and S-100 protein, indicating their myoepithelial cell differentiation. Chromosome analyses showed numeral abnormalities such as 5n ploidies and various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9;13)(p13.3;q12.3) was shared by all five of the cell systems. In addition, they all had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which resulted in generation of its nonsense gene product. Transplanted cells in nude mice formed subcutaneous tumors, which had histological features of squamous cell carcinoma with apparent keratinizing tendencies. In addition, they had ductal arrangements or plasmacytoid appearances of tumor cells and myxoid or hyaline stromata, indicating some characteristics of pleomorphic adenoma.
Conclusion
This study demonstrates in vitro that certain cell types from pleomorphic adenoma are able to clone and survive over a long term and develop subcutaneous tumors in nude mice. The histological features of squamous cell carcinoma from the transplanted cell systems in nude mice might suggest a secondary onset of malignancy from a pre-existing benign adenoma.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference40 articles.
1. Gnepp DR, Wening BM: Malignant mixed tumors. Surgical pathology of the Salivary Glands. Edited by: Ellis GL, Auclair PL, Gnepp DR. 1991, Philadelphia: W.B. Saunders, 350-368.
2. Ellis GL, Auclair PL: Tumor of the Salivary Glands: Atlas of Tumor Pathology, 3rd Series. 1996, Washington, DC: Armed Forces Institute of Pathology, 228-238.
3. Ohtaké S, Cheng J, Ida H, Suzuki M, Ohshiro K, Zhang W, Saku T: Precancerous foci in pleomorphic adenoma of the salivary gland: recognition of focal carcinoma and atypical tumor cells by P53 immunohistochemistry. J Oral Pathol Med. 2002, 31: 590-597. 10.1034/j.1600-0714.2002.00040.x.
4. Brandwein M, Huvos AG, Dardick I, Thomas MJ, Theise ND: Noninvasive and minimally invasive carcinoma ex mixed tumor: A clinicopathologic and ploidy study of 12 patients with major salivary tumors of low (or no?) malignant potential. Oral Surg Oral Med Oral Pathol Radiol Endod. 1996, 81: 655-664. 10.1016/S1079-2104(96)80071-0.
5. Auclair PL, Ellis GL: Atypical features in salivary gland mixed tumors: their relationship to malignant transformation. Mod Pathol. 1996, 9: 652-657.
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