Aylin Orgen ÇALLI, Neşe EKİNCİ, Ayşegül AKDER SARI, Filiz DAĞ

Mide adenokarsinomlarında p53 ekspresyonu ve diğer konvansiyonel prognostik faktörlerle ilişkisi

İnsan kanserlerinde tümör gelişimi ve tümör progresyonunun oluşumundan sorumlu tutulan çoğu genetik değişikliklerin temelinde p53 gen mutasyonlan rol oynar. Meme kanseri başta olmak üzere çoğu kanser tiplerinde p53 ekspresyonu ile prognoz arasında ilişki olmasına rağmen; mide karsinomlarında p53 geninin prognostik önemi hala kesinlik kazanmamıştır. Mide karsinomlu 70 hastanın formalinle fikse parafin kesitlerinde p53 ekspresyonu araştırıldı. Tüm olguların %31'inde p53 pozitifliği tespit edildi. İstatistiksel olarak p53 overekspresyonu ile tümör invazyon derinliği, lenf nodu tutulumu, tümör diferansiyasyon derecesi, damar ve lenfatik invazyon, yaş, cinsiyet ve tümör boyutu karşılaştırıldı. Histolojik diferansiyasyon dışında diğer prognostik faktörlerle p53 pozitifliği arasında istatistiksel olarak anlamlıilişki saptanmadı. Sadece intestinal tip gastrik karsinomlarda p53 ekspresyonunun prognostik önemi tespit edilmiş olmasına rağmen, p53 ekspresyonunun mide karsinomlarında prognostik değerinin olmadığıdüşünüldü.

Anahtar Kelimeler:

Gen ekspresyonu, Mide neoplazmları, İmmünohistokimya, Seyir, Adenokarsinom

Expression of p53 protein in adenocarcinomas of stomach and its relationship with other conventional prognostic factors

Mutations of the p53 gene belong to the most common genetic alterations in human cancer that have been implicated in tumorigenesis and tumor progression. Although p53 expression appears to be correlated with prognosis of breast cancer and some other types of cancer, its prognostic role in gastric cancer is stili uncertain. p53 gene expression was examined in formalin-fixed, paraffin-embedded tissue sections from 70 patients with gastric cancer. p53 expression was detected in 31% of ali tumors. The correlation of p53 over-expression and depth of invasion, lymph node involvement, degree of tumor differantion, blood vessel invasion, lymphatic vessel invasion, age , sex and tumor size was evaluated statistically. Significant relation was not noted between p53 expression and prognostic factors except histologic grade. These results indicate p53 expression seem to be important in the prognosis of only intestinal type of gastric carcinomas; hovvever, p53 protein accumulation was found to have no prognostic value in gastric tumors.

Keywords:

Gene Expression, Stomach Neoplasms, Immunohistochemistry, Prognosis, Adenocarcinoma,

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1. Cho JH, Kim WH. Altered Topographic expression of p21/WAF1/CIP1/SDI1,bcl2 and p53 during gastric carcinogenesis. Pathol Res Pract1998;194: 305-17
2. Morita M, Kuvano H, Baba Hideo, Taketomi A.Kohnoe S, Tomoda H, et al. Multifocal oocurence of gastnc carcinoma in patients with a family history of gastric carcinoma. Cancer 1998; 83:1307-11
3. Tahara E. Molecular Mechanism of Stomach Carcinogenesis. J Cancer Res Clin Oncol 1993; 119: 265-272
4. Tahara E. Genetic alterations in human gastrointestinal cancers: The application to molecular diagnosis. Cancer 1995; 75: 1410- 1417
5. Tahara E. Molecular Biology of Gastric Cancer. World J Surg 1995; 19: 484-490
6. Fielding IWL, Roginski C, Ellis DJ et ali: Clinicopathological staging of gastric cancer. Br J Surg 1984; 71: 677-680
7. Onaran, M.S ve ark. Türkiye Yüksek İhtisas Hastanesi Gastroenteroloji Cerrahisi Servisi Çalışmaları, kişisel görüşme ve yayınlamaya hazır veriler, Ankara, 1988
8. Goldman H, eds. Pathology of the Gastrointestinal Tract. Philadelphia: WB Saunders. 1992; 584-617
9. Hurlimann J, Saraga EP. Expression of p53 protein in gastric carcinomas. Association with histologic type and prognosis. Am J Surg Pathol 1994; 18(12): 1247-53
10. Starzynska T, Bromley M, Ghosh A, Stern PL. Prognostic significance of p53 overexpression in gastric and colorectal cancer Br J Cancer. 1992;66 (3):558-62.
11. Kakeji Y, Korenaga D, Tsujtani S, Baba H, Anai H, Machara Y, et ali. Gastric cancer with p53 overexpression has high potential for metastasing to lymph nodes. Brit J Cancer 1993; 67: 589-93
12. Yonemura Y, Fushida S, Tsuqawa K, Ninomiya I, Foncesa L, Yan A, Miyazaki I, Urano T, Shiku H. Correlation of p53 Expression and proliferative activity in gastric cancer. Anal Celi Pathol 1993; 5(5): 227-88
13. Sanz-Ortega J, Steinberg SM, Mora E, et al. Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-erbB- 2, c-myc and EGFras prognostic factors in gastric cancer. Histol histopathol. 2000: 15(2): 455-62
14. Stemmermann G, Heffelfinger SC, Noffsinger A, et ali. The molecular biology of eosophageal and gastric cancer and their precursors: Oncogenes and supressor genes and grovvth factors. Hum Pathol 1994; 25: 968-981
15. Yonemura Y, Takamura H, Ninomiya I, et ali: Interrelationship betvveen transforming grovvth factor alpha epidermal grovvth factor receptor in advanced gastic cancer. Oncology 1992; 49: 157-161
16. Zeren H, Kayaselçuk F, Coşar E, Tuncer i. Doku tespit solüsyonu ve süresinin Immunohistokimyaya yansıması. Ankara Patoloji Bülteni 1996; 13(1) : 87-91
17. Mountinho RM, Sarmento JA, Sabrinho SMA, Bastos J: Prognostic Significance of Lauren and Ming Classifications and other Pathologic Parameters in Gastric Carcinoma. Cancer 1981; 47: 780-4
18. Davessar K, Pezzullo JC, Kessimian N, Hale JH, Jau regvi HO. Gastric Adenocarcinoma: Prognostic Significance of Several Pathologic Parameters and Histologic Classifications. Human Pathology 1990; 21(3): 325-32
19. Martin HM, Filipe M, Morris RW, İane DP, Silvertre F. p53 expression in gastric and colorectal carcinoma. Brit J Cancer 1992; 66: 558-62
20. Joypaul BY, HopvvoodD, Nevvman EL, Oureshi S, Granî A, Ogston SA, et ali. The prognostic significance of the accumulation of p53 tumor supressor gene protein in gastric adenocarcinoma Brit J Cancer 1994; 69: 943-6
21. Roviello F, Marrelli D, Vindigni C, et al. p53 accumulation is a prognostic factor in intestinal-type gastric carcinoma but not in the diffuse type. Ann Surg Oncol 1999 ; 6(8): 739-451
22. lochim E, Goussia A, Stefanou D, Agnantis NJ. Expression of p53 protein in gastric cancer : an imrnunohistochemical study with correlation to proliferative activity. Anticancer Res. 1997;17(1A):513-7.
23. Gabbert HE, Müller W, Schneiders A, Hommel G. The Relationship of p53 Expression to the Prognosis of 418 Patients vvith Gastric Carcinoma. Cancer 1995; 76: 720-6
24. Wang LS, Wu CW, Hsieh MJ, Fahn HJ, Huang MH, Chien KY. Lymph node metastasis in patients vvith adenocarcinoma of gastric cardia. Cancer 1993; 71: 1948-53
25. Şerlin O, Keehn RJ, Higgins GA, Harrovver HW, Mendeloff GL. Factors related to survival follovving resection for gastric carcinoma. Analysis of 903 cases. Cancer 1977; 40: 1318-29
26. Hiroto T, Ming SC. Early Gastric Cancer. İn: Ming SC, Goldman H, eds. Pathology of the Gastrointestinal Tract. Philadelphia: WB. Saunders, 1992; 570-583
27. Harrison JC, Dean PJ, Wander Zvvaag R, el Zeky F, Wruble LD. Adenocarcinoma of the stomach vvith invasion limited to the muscularis propria. Hum Pathol 1991; 22: 111-7
29. Antonioli DA, Madara JL: Functional anatomy of the gastrointestinal tract. İn Ming SC, Goldman H, editors: Pathology of th gastrointestinal tract, Philadelphia: Saunders, 1992
29. Ichiyoshi Y, Oivva H, Tomisaki S, Sakaquchi Y, Ohno S, Maehara Y, Suqimachi K. Overexpression of p53 is associated vvith grovvth pattern and prognosis in advenced gastric cancer. Hepatogastroenterology 1997; 44(14): 546-553
30. Maehara Y, Tomoda M, Hasuda S, Kabahhima A, Takunaga E, Kakji Y, Suqimacki K, Prognostic value of p53 protein expression for patients vvith gastric cancer-a multivariate analysis. Br J Cancer 1999; 79(7-8): 1255-61
31. Lee WJ. Shun CT, Hong RL, Wu MS, Chang KJ, Chen KM. Overexpression of p53 predicts shorter survival in diffuse type gastic cancer. Br J Surg 1998: 85(8): 1138-42
32. Kennedy BJ: Staging of Gastric Cancer. Semin Oncol 1985; 1: 19-20
33. Jürgen D.R, Knut B, Rüdiger S, et ali: Prognostic factors in Gastric Carcinoma. Cancer 1993; 72: 2089-97
34. Tanaka, Watanabe T, Okuna K, Tasutom M: Perineural invasion or a predictor of recurrence of gastric cancer. Cancer 1994; 73: 550-553
35. Nakamura K, Ueyama T, Yao T, et ali. Pathology and prognosis of gastric carcinoma. Cancer 1992; 70: 1030-1037