Molecular Biologic Analysis of c-kit Gene in Salivary Gland Carcinoma

타액선암에서 c-kit 유전자에 대한 분자생물학적 연구

  • Seo Kyu-Hwan (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Jung Kwang-Yoon (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Woo Jung-Soo (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Baek Seung-Kuk (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Choi Sung-Bae (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Kim Sang-Hee (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Kim In-Sun (Department of Pathology, Korea University, College of Medicine) ;
  • Kwon Soon-Young (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine)
  • 서규환 (고려대학교 의과대학 이비인후과학교실) ;
  • 정광윤 (고려대학교 의과대학 이비인후과학교실) ;
  • 우정수 (고려대학교 의과대학 이비인후과학교실) ;
  • 백승국 (고려대학교 의과대학 이비인후과학교실) ;
  • 최성배 (고려대학교 의과대학 이비인후과학교실) ;
  • 김상희 (고려대학교 의과대학 이비인후과학교실) ;
  • 김인선 (고려대학교 의과대학 해부병리과학교실) ;
  • 권순영 (고려대학교 의과대학 이비인후과학교실)
  • Published : 2003.11.01

Abstract

Objectives: The c-kit gene encodes a transmembrane receptor-type tyrosine kinase, which is known to have a significant role in the normal migration and development of germ cells and melanocytes. In the previous studies of c-kit gene, c-kit expressions showed only in adenoid cystic carcinomas, lymphoepithelioma-like carcinomas and myoepithelial carcinomas, but not in others and mutation was not found in any types of salivary carcinoma. We investigate the c-kit expression which may be useful to differentiating adenoid cystic carcinomas from others, and mutation of the gene which may not be exist nor the mechanism of c-kit activation in salivary carcinomas. Material and Methods: The archival tissue samples from 42 salivary carcinomas of major and minor salivary glands were studied for c-kit expression by immunohistochemistry and gene mutation by polymerase chain reaction amplification and single strand conformational polymorphism. Results: The c-kit expressions were noted in 22/24 adenoid cystic carcinomas, 7/9 mucoepidermoid carcinomas, 2/3 acinic cell carcinomas, 3/4 malignant mixed tumors, and one undifferentiated carcinoma. The mutation of c-kit gene was found in 3/24 adenoid cystic carcinomas, 3/8 mucoepidermoid carcinomas, one acinic cell carcinoma, and 2/4 malignant mixed tumors. Conclusion: c-kit protein overexpression is seen in a variety of salivary gland carcinomas, and the mutation of the gene may be the mechanism of c-kit activation in these neoplasms.

Keywords

References

  1. Yarden Y, Kuang WJ, Yang-Feng T, et al : Human proto-oncogene c-kit : a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J 1987 ; 6 : 3341-3351
  2. Lammie A, Drobnjak: M, Gerald W, Saad A, Cote R, Cordon-Cardo C : Expression ofc-kit and kit ligand proteins in normal human tissues. J Histochem Cytochem 1994; 42 : 1417-1425 https://doi.org/10.1177/42.11.7523489
  3. Sekido Y, Obata Y, Ueda R, et al : Preferential expression of ckit protooncogene transcripts in small cell lung cancer. Cancer Res 1991 ; 51 : 2416-2419
  4. Pietsch T, Nicotra MR, Fraioli R, Wolf HK, Mottolese M, Natali PG : Expression of the c-kit receptor and its ligand SCF in nonsmall cell carcinomas. Int J Cancer 1998 ; 75 : 171-175 https://doi.org/10.1002/(SICI)1097-0215(19980119)75:2<171::AID-IJC1>3.0.CO;2-R
  5. Hirota S, Isozaki K, Moriyama Y, et al : Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998; 279 : 577-580 https://doi.org/10.1126/science.279.5350.577
  6. Ikeda H, Kanakura Y, Tamaki T, et al : Expression and junctional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells. Blood 1991 ; 78 : 2962-2968
  7. Hines SJ, Organ C, Komstein MJ, Krystal GW : Coexpression of the c-kit and stem cell factor genes in breast carcinomas. Cell Growth Differ 1995 ; 6 : 769-779
  8. Lasota J, Jasinski M, Sarlomo-Rikala M, Miettinen M : Mutations in Exon 11 of c-kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 1999 ; 154: 53-60 https://doi.org/10.1016/S0002-9440(10)65250-9
  9. Longley BJ, Tyrrell L, Lu SZ, et al : Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis : establishment of clonality in a human mast cell neoplasm. Nat Genet 1996 ; 12 : 312-314 https://doi.org/10.1038/ng0396-312
  10. Jeng YM, Lin CY, Hsu HC : Expression of the c-kit protein is associated with certain subtypes of salivary gland carcinoma. Cancer Lett 2000 Jun 1 ; 154(1) : 107-111 https://doi.org/10.1016/S0304-3835(00)00387-6
  11. Holst VA, Marshall CE, Moskaluk CA, Frierson HF Jr : KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma. Mod Pathol 1999 Oct; 12 (10) : 956-960
  12. Ehab YH, James YS : Neoplasms of the Salivary Glands. In : Cummings CW, Fredricson JM, Harker LA, et al (eds). Otolaryngology-Head and Neck Surgery, 3rd Ed. St. Louis : Mosby-Year Book, 1998, p1255-1302
  13. Pignataro L, Capaccio P, Carboni N, et al : p53 and cyclinX D1 protein expression in carcinomas of the parotid gland. Anticancer Res 1998 ; 18 : 1287-1290
  14. Deguchi H, Hamano H, Hayashi Y : c-myc, ras p21 and p53 expression in pleomorphic adenoma and its malignant form of the human salivary glands. Acta Pathol Jpn 1993 ; 43 : 413-422
  15. Kamio N : Coexpression of p53 and c-erbB-2 proteins is associated with histological type, tumour stage, and cell proliferation in malignant salivary gland tumours. Virchows Archiv 1996 ; 428: 75-83
  16. Gallo O, Franchi A, Bianchi S, Boddi V, Giannelli E, Alajmo E : p53 oncoprotein expression in parotid gland carcinoma is associated with clinical outcome. Cancer 1995 ; 75 : 2037-2044 https://doi.org/10.1002/1097-0142(19950415)75:8<2037::AID-CNCR2820750802>3.0.CO;2-V
  17. Sarlomo-Rikata M, Kovatich AJ, Barusevicius A, Miettine M : CD117 : a sensitive marker for gastrointestinal stromal tumors that is specific than CD34. Mod Pathol 1998 ; 11 : 728-734
  18. Tazawa K, Tsukada K, Makuuchi H, Tsutsumi Y : An immuno-histochemical and clinico-pathological study of gastrointestinal tumors. Pathol Int 1999 ; 49 : 786-798 https://doi.org/10.1046/j.1440-1827.1999.00947.x
  19. Demetri GD : Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571). Eur J Cancer 2002 Sep ; 38 Suppl 5 : S52-59