Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Expression of p53 and bcl-2 in Gastric Adenocarcinoma Affects the Prognosis and Survival Rate

위선암에서 p53과 bcl-2의 발현이 예후와 생존율에 미치는 영향

  • Hong, Jong-Hyun (Department of Surgery, Bundang Jesaeng General Hospital) ;
  • Shin, Dong-Woo (Department of Pathology, Bundang Jesaeng General Hospital) ;
  • Paik, So-Ya (Department of Surgery, Bundang Jesaeng General Hospital) ;
  • Kim, Il-Dong (Department of Surgery, Bundang Jesaeng General Hospital) ;
  • Kim, Ki-Ho (Department of Surgery, Bundang Jesaeng General Hospital) ;
  • Park, Jin-Soo (Department of Surgery, Bundang Jesaeng General Hospital) ;
  • Suh, Byung-Sun (Department of Surgery, Bundang Jesaeng General Hospital) ;
  • Kim, Sang-Wook (Department of Surgery, Bundang Jesaeng General Hospital) ;
  • Lim, Hye-In (Department of Surgery, Bundang Jesaeng General Hospital)
  • Published : 2009.09.30
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Abstract

Purpose: p53 and bcl-2 are important markers of apoptosis. The expression of p53 and bcl-2 in gastric adenocarcinoma was examined in relation to prognosis and survival rate. Materials and Methods: The clinicopathologic data from 238 patients who underwent gastrectomies for gastric adenocarcinoma between December 1999 and July 2007 were reviewed. Immunohistochemical staining of gastric adenocarcinoma tissues embedded in paraffin blocks was performed using an Envision kit (DAKO, Glostrup, Denmark). Statistical comparisons were made between age, gender, tumor invasion, lymph node metastasis, TNM stage, Lauren's classification, cell differentiation, and the relationship with p53 and bcl-2. Results: The expression of p53 was related to cell differentiation (P=0.028) and UICC TNM stage (P<0.001). The expression of bcl-2 was related to UICC TNM stage (P=0.005). The co-expression of p53 and bcl-2 was related to UICC TNM stage (P=0.002). The co-expression group exhibited a greater reduction in the survival rate (P=0.001). Conclusion: The expression of p53 and bcl-2 nuclear proteins has significant relationships with other conventional prognostic factors and the survival rate. bcl-2 will be characterized through analysis of a greater number of patients and comparison with survival data over a longer period of time.

목적: 세포자멸사의 중요인자인 p53과 bcl-2의 개별발현 및 동시 발현이 갖는 위선암의 예후 인자로서의 역할과 생존율에 미치는 영향을 알아보고자 하였다. 대상 및 방법: 1999년 12월에서 2007년 7월까지 위선암으로 분당제생병원 외과에서 근치적 위절제술을 시행 받은 238명의 환자들을 대상으로 자료의 후향적 분석을 시행하였다. p53과 bcl-2의 발현은 DAKO사의 Envision kit로 면역조직화학 염색을 하여 발현군을 양성으로 정의하였다. 결과: 전체 환자 중 p53은 149예(62.5%)에서 발현되었으며, 다른 임상병리학적 예후 인자와의 상관관계를 조사한 결과 세포분화도(P=0.028), TNM 병기(P<0.001)에서 유의성을 나타냈다. bcl-2은 29예(12.2%)가 발현되었으며, TNM 병기(P=0.005)에서 유의성을 나타냈다. 단변량 생존율 분석을 통해 p53과 bcl-2는 생존율 감소에 영향이 있으며, 다변량 생존율 분석을 통해 p53은 독립적 예후 인자로서의 확인되었다. 또한 두 단백의 동시 발현군도 TNM 병기(P=0.002)와 의미 있는 상관관계를 보였으며, 개별 발현 때보다 동시 발현 시 유의한 생존율 감소를 보였다(P<0.001). 결론: p53과 bcl-2의 개별 발현은 나쁜 예후를 나타내며, 이들의 동시 발현은 더욱 나쁜 예후를 나타냈다. 그러나 bcl-2는 다변량 분석에서 독립 예후인자로서 의미는 부족하여 더 많은 분석을 통해 명확히 할 필요가 있겠다.

Keywords

References

  1. Reed JC. Mechanisms of apoptosis. Am J Pathol 2000; 157:1415-1430. https://doi.org/10.1016/S0002-9440(10)64779-7
  2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
  3. Dematrios A. Oncogenes and tumor suppressor gene as paradigms in oncogenesis. J BUON 2007;12(Suppl 1):9s-12s.
  4. Ku KB, Park SH, Cheong HY, Yu W, Lee MH. p53 gene mutation in gastric cancer tissue. J Korean Gastric Cancer Assoc 2006;6:214-220. https://doi.org/10.5230/jkgca.2006.6.4.214
  5. Martin HM, Filipe MI, Morris RW, Lane DP, Silvestre F. p53 expression and prognosis in gastric carcinoma. Int J Cancer 1992;50:859-862. https://doi.org/10.1002/ijc.2910500604
  6. Ishida H, Irie K, Itoh T, Fukikawa T, Tokunaga O. The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with ki-67 growth fraction. Cancer 1997;80:1034-1045. https://doi.org/10.1002/(SICI)1097-0142(19970915)80:6<1034::AID-CNCR5>3.0.CO;2-9
  7. Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 1995;55:237-241.
  8. Zhao DP, Ding XW, Peng JP, Zheng YX, Zhang SZ. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B 2005;6:1163-1169. https://doi.org/10.1631/jzus.2005.B1163
  9. Faille A, De Cremoux P, Extra JM, Linares G, Espie M, Bourstyn E, De Rocquancourt A, Giacchetti S, Marty M, Calvo F. p53 mutations and overexpression in locally advanced breast cancers. Br J Cancer 1994;69:1145-1150. https://doi.org/10.1038/bjc.1994.225
  10. Ahrendt SA, Rashid A, Chow JT, Eisenberger CF, Pitt HA, Sidransky D. p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer. J Hepatobiliary Pancreat Surg 2000;7:426-431. https://doi.org/10.1007/s005340070039
  11. Puhalla H, Kandioler D, Ludwig C, Filipits M, Wrba F, Laengle F, Jakesz R, Gruenberger T. p53 analysis in gallbladder cancer: comparison of gene analysis versus immunohistochemistry. Anticancer Res 2004;24:1201-1206.
  12. Pezzella F, Turley H, Kuzu I, Tungekar MF, Dunnill MS, Pierce CB, Harris A, Gatter KC, Masom DY. bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med 1993;329: 690-694. https://doi.org/10.1056/NEJM199309023291003
  13. Manne U, Myers RB, Moron C, Poczatek RB, Dillard S, Weiss H, Brown D, Srivastava S, Grizzle WE. Prognostic significance of Bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma. Int J Cancer 1997;74:346-358. https://doi.org/10.1002/(SICI)1097-0215(19970620)74:3<346::AID-IJC19>3.0.CO;2-9
  14. Muller W, Schneiders A, Hommel G, Gabbert HE. Prognostic value of bcl-2 expression in gastric cancer. Anticancer Res 1998;18:4699-4704.
  15. Lauwers GY, Scott GV, Karpeh MS. Immunohistochemical evaluation of bcl-2 protein expression in gastric adenocarcinomas. Cancer 1995;75:2209-2213. https://doi.org/10.1002/1097-0142(19950501)75:9<2209::AID-CNCR2820750904>3.0.CO;2-M
  16. Inada T, Kikuyama S, Ichikawa A, Igarashi S, Ogata Y. Bcl-2 expression as a prognostic factor of survival of gastric carcinoma. Anticaner Res 1998;18:2003-2010.
  17. Aizawa K, Ueki K, Suzuki S, Yabusaki H, Kanda T, Nishimaki T, Suzuki T, Hatakeyama K. Apoptosis and Bcl-2 expression in gastric carcinoma: correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis. Int J Oncol 1999;14:85-91.
  18. Yi SH, Kim HC, Lee SH, Park HC, Yoon C, Joo HZ, Choi BK, Choi JM. Multivariate analysis of prognostic factors in gastric cancer. J Korean Surg Assoc 1999;56:75-83.
  19. Maruyama K. The most important prognostic factors for gastric cancer patients: a study using univariate and multivariate analyses. Scandinavian J Gastroenterol 1987;22:63-68. https://doi.org/10.3109/00365528709091021
  20. Tahara E. Gene alterations in human gastrointestinal cancers. The application to molecular diagnosis. Cancer 1995;75(Suppl 6):1410s-1417s. https://doi.org/10.1002/1097-0142(19950315)75:6+<1410::AID-CNCR2820751504>3.0.CO;2-O
  21. Motojima K, Furui J, Kohara N, Ito T, Kanematsu T. Expression of p53 protein in gastric carcinomas is not independently prognostic. Surgery 1994;116:890-895.
  22. Union International Contre la Cancrum. UICC TNM Classification of Malignant Tumors. 5th ed. New York: Wilwy-Liss, 1997.
  23. Haldar S, Negrini M, Monne M, Sabbioni S, Croce CM. Downregulation of bcl-2 by p53 in breast cancer cells. Cancer Res 1994;54:2095-2097.
  24. Hurlimann J, Larrinaga B, Vala DL. bcl-2 protein in invasive ductal breast carcinomas. Virchows Arch 1995;426:163-168.
  25. Watson AJ, Merritt AJ, Jones LS, Askew JN, Anderson E, Becciolini A, Balzi M, Potten CS, Hickman JA. Evidence of reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas. Br J Cancer 1996;73:889-895. https://doi.org/10.1038/bjc.1996.178