#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Immunohistochemical expression of C-kit oncoprotein in salivary gland carcinomas (A pilot study)


Authors: I. Stárek 1;  L. Kučerová 2;  A. Skálová 3;  M. Brož 1;  T. Bakaj 1;  K. Langová 4
Authors‘ workplace: Klinika ORL a chirurgie hlavy a krku LF UP a FN, Olomouc, přednosta prof. MUDr. I. Stárek, CSc. 1;  Ústav patologie, FN Olomouc, přednosta doc. MUDr. M. Tichý, CSc. 2;  Ústav patologie, FN Plzeň, přednosta prof. MUDr. M. Michal 3;  Ústav lékařské biofyziky LF UP, Olomouc, přednostka doc. RNDr. H. Kolářová, Ph. D. 4
Published in: Otorinolaryngol Foniatr, 59, 2010, No. 3, pp. 129-135.
Category: Original Article

Overview

Background:
To investigate the expression of c-kit protein in salivary gland carcinomas and to correlate it to prognosis.

Methods:
Immunohistochemistry for c-kit protein was performed in 33 carcinomas, using formalin-fixed paraffin-embedded sections. For the evaluation of reactivity of tumor cells, a combination of the cytoplasmic and/or membranous staining and the percentage of positive cells were applied. Only cases without any staining pattern were considered negative. For prognostic correlation, univariate disease-specific survival curves were calculated by the Kaplan-Meier method and distributions were compared using the log-rank test.

Results:
Of all 33 cases, only 7 were c-kit negative, including 3 low-grade mucoepidermoid carcinomas, 2 carcinomas ex pleomorphic adenoma and 1 secretory carcinoma and 1 low-grade cribriform cystadenocarcinoma. The group of 26 (i.e. 79 %) positive tumors was dominated by 9 adenoid cystic carcinomas (all but one revealing strong reaction), followed by 5 acinic cell, 3 each mucoepidermoid and salivary duct carcinoma, 2 carcinomas ex pleomorphic adenoma and 4 other tumors, in which positive staining ranged from 50-100 %, with the immunoreaction varying from weak to strong. Disease specific survival in c-kit negative (n=7) carcinomas did not differ from that in positive (n=26) cases.

Conclusions:
Of all salivary gland carcinomas, only adenoid cystic carcinoma was regularly associated with strong c-kit expression. Immunoreactivity in other subtypes, considering our as well as published data, greatly varies. C-kit expression harbors no significant prognostic information.

Key words:
c-kit oncoprotein, salivary gland carcinoma, prognosis.


Sources

1. Akin, C., Metcalfe, D. D.: The biology of Kit in disease and the application of pharmacogenetics. J. Allergy Clin. Immunol., roč. 114, 2004, s. 13-19.

2. Andreadis, D., Epivatianos, A., Poulopoulos, A. et al.: Detection of C-kit (CD117) molecule in benign and malignant salivary gland tumours. Oral. Oncol., roč. 42, 2006, č. 1, s. 57-65.

3. Arber, D. A., Tamaro, R., Weiss, L. M.: Paraffin section detection of the c-kit gene product (CD117) in human tissue: value in the diagnosis of mast cell disorders. Hum. Pathol., roč. 29, 1998, č. 5, s. 498-504.

4. Ashman, L. K.: The biology of stem cell factor and its receptor C-kit. Int. J. Biochem. Cell Biol., roč. 31, 1999, č. 10, s.1037-1051.

5. Bell, R., Dierks, E. J., Potter, B. E.: Management and outcome of patients with malignant salivary gland tumors. J. Oral Maxillofac. Surg., roč. 63, 2005, s. 917-928.

6. Beltran, D., Faquin, W. C., Gallagher, G. et al.: Selective immunohistochemical comparison of polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma. J. Oral Maxillofac. Surg., roč. 64, 2006, č. 3, s. 415-423.

7. Di Palma, S., Skálová, A., Vaněček, T. et al.: Non-invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER-2/neu and MIB1 immunohistochemistry. Histopathol., roč. 46, 2005, č. 2, s.144-152.

8. Druker, B., Talpaz, M., Resta, D. J. et al.: Efficacy and safety of a specific inhibitor of the CBR-ABL tyrosin kinase in chronic myeloid leukemia. N. Engl. J. Med., roč. 344, 2001, s. 1031-1037.

9. Edwards, P. C., Bhuiya, T., Kepech, R. D.: C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontics., roč. 95, 2003, č. 5, s. 586-593.

10. Ettl, T., Schwarz, N., Hartmann, A. et al.: Overexpression of EGFR and absence of C-KIT expression correlate with poor prognosis in salivary gland carcinomas. Histopathol., roč. 53, 2008, č. 5, s. 567-577.

11. Faivre, S., Raymond, E., Casiraghi, O. et al.: Imatinib mesylate can induce objective response in progressing, highly expressing KIT adenoid cystic carcinoma of the salivary glands. J. Clin. Oncol., roč. 23, 2005, s. 6271-6273.

12. Frankenthaler, R. A., Luna, M. A., Lee, S. S.: Prognostic variables in parotid gland cancer. Arch. Otolaryngol. Head Neck Surg., roč. 117, 1991, s. 1251-1256.

13. Freier, K., Flechtenmacher, C., Walch, A. et al.: Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland. Oral Oncol., roč. 41, 2005, č. 9, s. 934-939.

14. Heinrich, M. C., Corless, C. L., Demeteri, G. D. et al.: Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol., roč. 21, 2003, s. 4342-4349.

15. Holst, V. A., Marshall, C. E., Moskaluk, C. A. et al.: KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma. Mod. Pathol., roč. 12, 1999, č. 10, s. 956-960.

16. Hong, S. M., Hwang, I., Song, D. E. et al.: Clinical and prognostic significances of nuclear and cytoplasmic KIT expressions in extrahepatic bile duct carcinomas. Mod. Pathol., roč. 20, 2007, s. 562-569.

17. Hotte, S. J., Winquist, E. W., Lamont, E.: Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: A Princess Margaret Hospital phase II consortium study. J. Clin. Oncol., roč. 23, 2008, č. 3, s. 585-590.

18. Chandan, V. S., Wilbur, D., Faquin, W. C. et al.: Is c-kit (CD117) immunolocalization in cell block preparations useful in the differentiation of adenoid cystic carcinoma from pleomorphic adenoma? Cancer (Cancer Cytopathol), roč. 102, 2004, s. 207-209.

19. Jeng, Y. M., Lin, Ch. Y., Hsu, H. Ch.: Expression of the c-kit protein is associated with certain subtypes of salivary gland carcinoma. Cancer Letters, roč. 154, 2000, s. 107-111.

20. Juany, E., Nocka, K., Beier, D. R. et al.: The hematopoetic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell, roč. 63, 1990, č. 1, s. 225-233.

21. Lammie, A., Drobnjak, M., Gerald, W. et al.: Expression of c-kit and kit ligand proteins in normal human tissues. J. Histochem. Cytochem., roč. 42, 1994, č. 11, s. 1417-1425.

22. Lima, R. A., Tavares, M. R., Dias, F. L. et al.: Clinical prognostic factors in malignant parotid gland tumors. Otolaryngol. Head Neck Surg., roč. 133, 2005, s. 702-708.

23. Miliaras, D., Karasavvidou, F., Papanikolaou, A. et al.: KIT expression in fetal, normal adult and neoplastic renal tissues. J. Clin. Pathol., roč. 57, 2004, s. 463-466.

24. Pfeffer, M. R., Talmi, Y., Catane, R. et al.: A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands. Oral Oncol., roč. 43, 2007, s. 33-36.

25. Rohr, U. P., Rehfeld, N., Pflugfelder, L. et al.: Expression of the tyrosine kinase c-kit is an independent prognostic factor in patients with small cell lung cancer. Int. J. Cancer, roč. 111, 2004, s. 259-263.

26. Sattler, M., Salgia, R.: Targeting c-Kit mutations: basic science to novel therapies. Leuk. Res., roč. 28 (Suppl. 1), 2004, s. 11-20.

27. Seethala, R. R., Hunt, J. L., Baloch, Z. W. et al.: Adenoid cystic carcinoma with high-grade transformation. A report of 11 cases and a review of the literature. Amer. J. Surg. Pathol., roč. 31, 2007, č. 11, s. 1683-1694.

28. Schmandt, R. E., Broaddus, R., Lu, K. H. K. et al.: Expression of c-ABL, c-KIT, and platelet derived growth factor receptor-beta in ovarian serous carcinoma and normal ovarian surface epithelium. Cancer, roč. 98, 2003, č. 4, s. 758-764.

29. Simak, R., Capodieci, P., Cohen, D. W. et al.: Expression of c-kit and kit-ligand in benign and malignant prostatic tissues. Histol. Histopathol., roč. 15, 2000, č. 2, s. 765-374.

30. Skálová, A., Stárek, I., Vaněček, T. et al.: Expression of HER2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluoresence in situ hybridisation immunohistochemisty. Histopathol., roč. 42, 2003, č. 4, s. 348-356.

31. Skálová, A., Vaněček, T., Šíma, R. et al.: Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Amer. J. Surg. Pathol., roč. 34, 2010, č. 5, s. 599-608.

32. Sorensen, K. B., Godballe, C., de Stricker, K. et al: Parotid carcinoma: expression of kit protein and epidermal growth factor receptor. J. Oral Pathol. Med., roč. 35, 2006, s. 286-291.

33. Stanula, M., Weite, K., Hadam, M. R. et al.: Coexpression of stem cell factor and its receptor c-Kit in human malignant glioma cell lines. Acta Neuropathol., roč. 89, 1995, č. 2, s. 158-165.

34. Tsutsui, S., Yasuda, K., Suzuji, K. et al.: A loss of c-kit expressions is associated with an advanced stage and poor prognosis in breast cancer. Br. J. Cancer, roč. 94, 2006, s. 1874-1878.

35. Tsuura, Y., Hiraki, H., Watanabe, K. et al.: Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed, paraffin embedded tissues. Virchows Arch., roč. 424, 1994, č. 2, s. 35-41.

36. Ulivi, P., Zoli, W., Medri, L. et al.: C-kit and SCF expression in normal and tumor breast tissue. Breast Cancer Res. Treat., roč. 83, 2004, č. 1, s. 33-42.

37. Van Oosterom, A. T., Judein, I., Verweij, J. et al.: Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet, roč. 358, 2001, s. 1421-1423.

38. Vila, L., Liu, H., Al-Quran, S. Z. et al.: Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. Mod. Pathol., roč. 22, 2009, č. 10, s. 1296-1302.

39. Vitali, R., Cesi, V., Nicotra, M. R. et al.: C-Kit is preferentially expressed in MYCN-amplified neuroblastoma and its effect on cell proliferation is inhibited in vitro by STI-571. Int. J. Cancer, roč. 106, 2003, č. 2, s. 147-152.

40. Went, P. T., Dirnhofer, S., Bundi, M. et al.: Prevalence of KIT expression in human tumors. J. Clin. Oncol., roč. 22, 2004, s. 4514-4522.

41. Zsebo, K. M., Williams, D. A., Geissler, E. N. et al.: Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell, roč. 63, 1990, č. 1, s. 213-224.

Labels
Audiology Paediatric ENT ENT (Otorhinolaryngology)
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#