타액선 종양에서 종양증식 관련인자 발현에 관한 면역조직화학적 연구

IMMUNOHISTOCHEMICAL STUDY ON EXPRESSION PATTERNS OF TUMOR GROWTH RELATED FACTORS IN SALIVARY GLAND TUMORS

  • 김한석 (강릉대학교 치과대학 구강악안면외과학교실) ;
  • 김성민 (강릉대학교 치과대학 구강악안면외과학교실) ;
  • 박영욱 (강릉대학교 치과대학 구강악안면외과학교실)
  • Kim, Han-Seok (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University) ;
  • Kim, Soung-Min (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University) ;
  • Park, Young-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University)
  • 발행 : 2007.09.30

초록

Objective : Lots of papers have revealed that tumor growth related factors such as EGF, EGFR, c-erbB-2 play an important role in tumorigenesis and proliferation. These factors are found in most tumors of ectodermal origin. But, documentations of tumor growth related factors on salivary gland tumors were rare. Therefore, we determined expressions of tumor growth related factors; PCNA, p53, EGF, EGFR, cerbB2(HER-2), Maspin, DMBT-1, N-Ras in representative salivary gland tumors. Materials and methods : A few types of salivary tumors were examined by immunohistochemical assays. Each antibody was applied to specimens of tumors. Specimens were composed of 5 pleomorphic adenomas (PA), 3 mucoepidermoid carcinomas (MEC), 2 adenoid cystic carcinomas (ACC) and 2 squamous cell carcinomas (SCC) from 12 patients. One specimen was selected randomly as negative control. For evaluation of staining intensity, each stained sample was divided into 5 grade; no staining, obscure, weak staining, moderate staining, strong staining. Results : Strong expressions of PCNA were found in all tumors except of PA. EGF was expressed strongly in SCC, ACC sequently. But in both PA and MEC, EGF expression was weak. EGFR and c-erbB-2 expression showed similar patterns in all salivary gland tumor tissues. P53 showed weak expression generally in all salivary gland tumors. DMBT-1 was expressed in SCC rather than in ACC or in MEC. N-Ras showed weak expressions in all salivary gland tumors except of squamous cell carcinoma. Conclusion : Taken together, tumor growth related factors were expressed in salivay tumors as well as mucosal squamous cell carcinoma. Especially EGFR and c-erbB-2 could be candidates as diagnostic markers for estimating clinical grade of salivary gland tumors. But further studies with reliable methods will be needed to confirm the results of this study.

키워드

참고문헌

  1. Fordice J, Kershaw C, El-Naggar A et al : Adenoid cystic carcinoma of the head and neck: predictor of morbidity and mortality. Arch Otolaryngol Head and neck 125 : 149, 1999 https://doi.org/10.1001/archotol.125.2.149
  2. Friedman EW, Schwartz AE : Diagnosis of salivary gland tumors. Cancer 24 : 266, 1974 https://doi.org/10.1002/1097-0142(196908)24:2<266::AID-CNCR2820240209>3.0.CO;2-#
  3. Wang JL, Zheng BY, Li XD et al : Predictive significance of the alterations of p16INK4A, p14ARF, p53, and proliferating cell nuclear antigen expression in the progression of cervical cancer. Clinical Cancer Research 10 : 2407, 2004 https://doi.org/10.1158/1078-0432.CCR-03-0242
  4. Thomas GR, Nadiminti H, Regalado J : Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int. J. Exp. Path. 86 : 347, 2005 https://doi.org/10.1111/j.0959-9673.2005.00447.x
  5. Khazaie K, Schirrmacher V, Lichtner RB : EGFreceptor in neoplasia and metastasis. Cancer Metastasis Rew 12 : 255, 1993 https://doi.org/10.1007/BF00665957
  6. Miettinen PJ, Berger JE, Meneses J et al : Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376 : 337, 1995 https://doi.org/10.1038/376337a0
  7. Threadgill DW, Dlugosz AA, Hansen LA et al : Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 269 : 230, 1995 https://doi.org/10.1126/science.7618084
  8. Sibilia M, Wagner EF : Strain-dependent epithelial defects in mice lacking the EGF receptor. Science 269 : 234, 1995 https://doi.org/10.1126/science.7618085
  9. Troyer KL, Lee DC : Regulation of mouse mammary gland development and tumorigenesis by the ERBB signaling network. J Mammary Gland Biol Neoplasia 6 : 7, 2001 https://doi.org/10.1023/A:1009560330359
  10. Maarten L, Janmaat ML, Giuseppe G : Small-molecule Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. The Oncologist 8 : 576, 2003 https://doi.org/10.1634/theoncologist.8-6-576
  11. Bruns CJ, Solorzano CC, Harbistone MT et al : Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res 60 : 2926, 2000
  12. Radinsky R, Risin S, Fan D et al : Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin cancer Res 1 : 19, 1995
  13. Salomon DS, Brandt R, Ciardiello F et al : Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19 : 183, 1995 https://doi.org/10.1016/1040-8428(94)00144-I
  14. Dziemianczyk D, Grabowska SZ, Czyzewska E et al : wybrane aspekty biochemiczne I fizjologiczne. Czas Stomat 53 : 656, 2000
  15. Prime SS, Game SM, Matthews JB et al : Epidermal growth factor and transforming growth factor alpha characteristics of human oral carcinoma cell lines. Br J Cancer 69(1) : 8, 1994 https://doi.org/10.1038/bjc.1994.2
  16. Partridge M, Kiguwa S, Emilion G et al : New insight into p53 protein stabilisation in oral squamous cell carcinoma. Oral Oncol 35 : 45, 1999 https://doi.org/10.1016/S1368-8375(98)00051-7
  17. Soengas MS, Capodieci P, Polsky D et al : Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 409 : 207, 2001 https://doi.org/10.1038/35051606
  18. Balajee AS, Geard CR : Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells. Nucleic Acid Research 29 : 1341, 2001 https://doi.org/10.1093/nar/29.6.1341
  19. Tsuji T, Mimura Y, Wen S et al : The significance of PCNA and p53 protein in some oral tumours. Int J Oral Maxillofac Surg 24 : 221, 1995 https://doi.org/10.1016/S0901-5027(06)80132-3
  20. Maass N, Hojo T, Rosel F et al : Down regulation of the tumor suppressor gene maspin in breast carcinoma is associated with a higher risk of distant metastasis. Clinical Biochemistry 34 : 303, 2001 https://doi.org/10.1016/S0009-9120(01)00220-X
  21. Sheng S, Carey J, Seftor EA et al : Maspin acts at the cell membrane to inhibit invasion and motility of mammary and prostatic cancer cells. Proc Natl Acad Sci USA 93 : 11669, 1996
  22. Mollenhauer J, Wiemann S, Scheurlen W et al : DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours. Nat. Genet. 17 : 32, 1997 https://doi.org/10.1038/ng0997-32
  23. Wu W, Kemp BL, Proctor ML et al : Expression DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer. Cancer Res. 59 : 1846, 1999
  24. Takeshita H, Sato M, Shiwaku HO et al : Expression of the DMBT1 gene is frequently suppressed in human lung cancer. Jpn J. Cancer Res. 90 : 903, 1999 https://doi.org/10.1111/j.1349-7006.1999.tb00833.x
  25. Mori M, Shiraishi T, Tanaka S et al : Lack of DMBT1 expression in oesophageal, gastric and colon cancers. Br. J. Cancer 79 : 211, 1999 https://doi.org/10.1038/sj.bjc.6690035
  26. Boguski MS, McCormick F : Proteins regulating Ras and its relatives. Nature 366 : 643, 1993 https://doi.org/10.1038/366643a0
  27. Zhang XF, Settleman J, Kyriakis JM et al : Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature 364 : 308, 1993 https://doi.org/10.1038/364308a0
  28. Lowy DR, Willumsen BM : Function and regulation of Ras. Annu Rev Biochem 62 : 851, 1993 https://doi.org/10.1146/annurev.bi.62.070193.004223
  29. Park YW, Kim JH : Immunohistochemiocal assays for the expression of epidermal growth factor-signaling proteins in adenoid cystic carcinomas of human salivary glands. J Kor Acad Maxillofac Plast Reconstr Surg 28 : 499, 2006
  30. Shiratsuchi T, Ishibashi H, Shirasuna K : Inhibition of Epidermal growth factor-induced invasion by Dexamethasone and AP-1 Decoy in Human Squamous Cell Carcinoma Cell Lines. J of Cellular physiology 193 : 340, 2002 https://doi.org/10.1002/jcp.10181
  31. Grunwald V, Hidalgo M : The epidermal growth factor receptor: a new target for anticancer therapy. Curr Probl Cancer 26 : 109, 2002
  32. Chen IH, Chang JH, Liao CT : Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area. British J of Cancer 89 : 681, 2003 https://doi.org/10.1038/sj.bjc.6601171
  33. Maubec E, Duvillard P, Velasco V : Immunohistochemical Analysis of EGFR and HER-2 in patients with Metastatic Squamous Cell Carcinoma of the skin. Anticancer Research 25 : 1205, 2005
  34. Sorensen KB, Godballe C. Stricker K et al : Parotid carcinoma: expression of kit protein and epidermal growth factor receptor. J Oral Pathol Med 35 : 286, 2006 https://doi.org/10.1111/j.1600-0714.2006.00421.x
  35. Kiyoshima T, Shima K, Kobayashi I et al : Expression of p53 tumor suppressor gene in adenoid cystic and mucoepidermoid carcinomas of the salivary glands. Oral Oncology 37 : 315, 2001 https://doi.org/10.1016/S1368-8375(00)00083-X
  36. Paterson IC, Eveson JW, Prime SS : Molecular changes in oral cancer may reflect aetiology and ethnic origin. Oral Oncol Eur J Cancer 32B : 150, 1996
  37. Baker SJ, Preisinger AC, Jessup JM et al : p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 50 : 7717, 1990
  38. Scarpa A, Capelli P, Mukai K et al : Pancreatic adenocarcinomas frequently show p53 gene mutations. Am J Pathol 142 : 1534, 1993
  39. Xia W, Lau YK, Mickey CT et al : High tumoral maspin expression is associated with improved survival of patients with oral squamous cell carcinoma. Oncogene 19 : 2398, 2000 https://doi.org/10.1038/sj.onc.1203535
  40. Sugimoto S, Maass N, Takimoto Y et al : Expression and regulation of tumor suppressor gene maspin in human bladder cancer. Cancer Letters 203 : 209, 2004 https://doi.org/10.1016/j.canlet.2003.09.010
  41. Braidott P, Nuciforo PG, Mollenhauer J et al : DMBT1 expression is down-regulated in breast cancer. BMC cancer 4 : 46, 2004 https://doi.org/10.1186/1471-2407-4-46
  42. Sasaki M, Huang SF, Chen MF et al : Decreased of Deleted in Malignant Brain Tumor-1(DMBT-1)expression is a crucial late event in intrahepatic cholangiocarcinoma. Histopathology 43 : 340, 2003 https://doi.org/10.1046/j.1365-2559.2003.01719.x
  43. Midgley RS, Kerr DJ : Ras as a target in cancer therapy. Hematology 44 : 109, 2002