Immunohistochemical Analysis of p53, Ki-67, CD44, HER-2/neu Expression Patterns in Gastric Cancer, and Their Association with One Year Survival in North-West of Iran
-
Zohreh Sanaat
,
Monireh Halimi
,
Morteza Ghojezadeh
,
Amir Hossein Pirovi
,
Jalil Vaez Gharamaleki
,
Ali Esfahani
,
Iraj Aswadi Kermani
,
Jamal Eivazi Ziae
Abstract
Introduction: Gastric cancer remains the second most common cause of cancer-related deaths worldwide. In many malignancies like, lung and breast, multiple prognostic factors are known, such as mutations in Ki-67, HER-2/neu, p53. In this study, we evaluated immunohistochemical protein expression patterns of cell-cycle-regulators p53, proliferation marker Ki-67, surface expression of CD44, HER-2/neu oncogene proposed as useful prognostic factors.
Methods: In this descriptive-analytic study, we evaluate 100 patients with gastric cancer who were referred to Shahid Ghazi Hospital or other oncology clinics of Tabriz University of Medical Sciences in 2005-2010. Patients with pathologic confirmation of gastric cancer were selected. Expression of p53, ki-67, CD-44, HER-2/neu were detected by immunohistochemical staining.
Results: In this study, 100 patients with gastric cancer participated. 76(76%) were men and 24(24%) were women with mean age of 64.02(8.05) years. Seventy two samples were intestinal type and 28 were diffuse type. CD44 was positive in 27(27%) patients. P53 was positive in 35(35%) patients. Ki-67 was positive in 53(53%) patients. HER-2/neu was positive in 51(51%) patients.
Conclusion: The frequency of positive p53, Ki-67, CD44 and HER-2/neu varied in different studies. Positive Ki-67 and HER-2/neu were not associated with changes in survival but positive p53 and CD44 were significantly associated with improved survival.
Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med.1995; 333: 32 – 41.
Kato Y, Nakamura S, Arai K, Konishi T, Takeshita K,Sano T, et al. Meeting report: the 75th Congress of the Japanese Gastric Cancer Association. Gastric Cancer.2004; 7: 3 – 8.
Morales TG. Adenocarcinoma of the gastric cardia. Dig Dis. 1997; 15: 346 – 356.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial progression. Cancer Res. 1992; 52:6735 – 6740.
Parsonnet J, Friedman GD, Vandersteen DP, Chang Y,Volgeman JH, Orentreich N, et al. Helicobacter pylori infection and risk of gastric carcinoma. N Engl J Med.1991; 325: 1127 – 1131.
Tredaniel J, Boffetta P, Buiatti E, Saracci R, Hirsch A.Tobacco smoking and gastric cancer: review and metaanalysis.Int J Cancer. 1997; 72: 565 – 573.
DaVita Vincent T., Lawrence, Theodore S., Rosenberg, Steven A. DaVita, Hellman & Rosenberg's Cancer, Principles & Practice of Oncology, 8th Edition, Lippincott Williams & Wilkins.2008;989-992.
Smith MG, Hold GL, Tahara E, El-Omar EM.Cellular and molecular aspects of gastric cancer. World J Gastroenterol . 2006; 12:2979–2990.
Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol .2006; 12:354–362.
Milner J, Watson JV. Addition of fresh medium induces cell cycle and conformational changes in p53, a tumor suppressor protein. Oncogene. 1990; 5: 1683 – 1690.
Azarhoush R, Keshtkar AA, Amiriani T, Kazemi-Nejad V.Relationship between p53 Expression and Gastric Cancers in Cardia and Antrum. Arch Iran Med, 2008; 11(5):502-6.
Staib f, Robeles AI, Varticovski l, WangXW.The tumor suppressor network is a key responder to microinvironmental components of chronic inflammatory stress.cancer res, 2005; 65(22):122-55.
Jovanović I, Todorović V, Milosavljević T, Micev M, Pesko P"et al".Expression of p53 protein in Barrett's adenocarcinoma and adenocarcinoma of the gastric cardia and antrum. Vojnosanit Pregl, 2005; 62(12):879-85.
Al-Moundhri MS, Nirmala V, Al-Hadabi I, Al-Mawaly K, Burney I," et al. The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/HER-/neu, and KI-67 proteins expression in gastric cancer: a clinic pathological and Immunohistochemical study of 121 Arab patients. J Surg Oncol, 2005; 15; 91(4):243-52.
Park DI, Yun JW, Park JH, Oh SJ, Kim HJ," et al".HER-2/neuamplification is an independent prognostic factor in gastric cancer. Dig Dis Sci, 2006; 51(8):1371-9.
Orita H, Maehara Y, Emi Y, Kakeji Y, Baba H, Korenaga D,Sugimachi K. c-erbB-2 expression is predictive for lymphatic spread of clinical gastric carcinoma. Hepatogastroenterology.1997; 44:294–298.
Joo M, Lee HK, Kang YK.Expression of E-cadherin, beta-catenin, CD44s and CD44v6 in gastric adenocarcinoma: relationship with lymph node metastasis. Anticancer Res, 2003; 23(2B):1581-8.
Hsieh HF, Yu JC, Ho LI, Chiu SC, Harn HJ. Molecular studies into the role of CD44 variants in metastasis in gastric cancer.Mol Pathol, 1999; 52(1):25-8.
Sneath RJ, Mangham DC. The normal structure and function of CD44 and its role in neoplasia. Mol Pathol, 1998; 51(4):191-200.
wakamatsu Y,Sakamoto N,Oo Hz.Expresion of cancer stem cell markers ALDH1,CD44, and CD133 in primary tumor and lymph node metastasis of gastric cancer;pathol Int.2012;62(2):112-9.
Byung Ik Jang,* Yuan Li,* David Y. Graham,* and Putao Cen. The Role of CD44 in the Pathogenesis, Diagnosis, and Therapy of Gastric Cancer. Gut Liver, 2011; 5(4): 397–405.
Shigeo T,Tomoyuki O,Shiuping TSophie S.Wataru S,Ramanathan V"et al.Identification of gastric cancer stem cells using the cell surface marker CD44.alphaMed Press,2009;l27(5), 1006-1020.
Shafigh E, Abdolazimi Y, Shafaie Sh, Hajiahmadi M. Expression of biomarkers Ki-67, p27KIP1,p53 in gastric cancer andtheir association with histopathologic indicators of gastrectomy samples of patients reffered to Shahid Beheshti hospital Babol Iran in2000-2006. Univ Med Scienc Babol. 2007; 9(4):7.
Yao zheng, Lin wang, Jian-ping.expression of p53, c-erbB and KI-67 in intestinal met aphasia and gastric carcinoma.world j gastroenterol, 2010: 21; 13(23):3189-98.
Shiao YH, RuggeM.p53 alteration in gastric precancerous lesions.Am J Pathol.1994; 144(3):511.
LI JH, Shi XZ,Lv S, Liu M(2005).Effect of helicon bacter on p53 expression of gastric mucosa and adenocarcinoma with micro satellite instability.World J Gastroenterol,2005;11(28):4363.
N E Tzanakis, G Peros,P Karakitsos.(2009).prognostic significans of p53 and KI-67 proteins expression in Greek gastric cancer patients.ActaChirurgica Belgica,2009;109(5):606-611.
Wanyi Tai, Rubi Mahato, and Kun Cheng.The role of HER-2/NEU in cancer therapy and targeted drug delivery. J Control Release, 2010; 15; 146(3): 264–275.
Cathy B.Moelans, Paul J. van Diest, Anya N Milne, and G. Johan A. Offerhaus. SAGE-Hindawi .Access to Research Pathology Research International, 2011:10.
Fredrik Petersson, Kurt Borch , Lennart E. Franzén. Gastric Epithelial Proliferation and p53 and p21 Expression in a General Population SampleRelations to Age, Sex, and Mucosal Changes Associated with H. pylori Infection.Digestive disease and science, 2006; 47(7)145-56.
28 Gomyo Y, Ikeda M, Osaki M, et al.Expression of P21 (waf1/cip1/sdi1), but not P53 protein, is a factor in the survival of patients with advanced gastric carcinoma. Cancer, 1997; 79(11): 2067-72.
E. U. Cidon, R. G. Centeno, E. G. Lagarto, J. I. Peral. HER-2 Evaluation in a Specific Gastric Cancer Population with the Highest Rate of Mortality in Spain. Journal of Oncology, 2011: 6.
Shi-Yan Yan, Ying Hu, Jian-Gao Fan, Guo-Quan Tao, Yong-Ming Lu, Xu Cai, Bao-Hua Yu, Yi-Qun Du.Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma. World J Gastroenterol. 2011;17(11): 1501-1506
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| Issue | Vol 7, No 3 (2013) | |
| Section | Articles | |
| Keywords | ||
| CD-44 Gastric cancer HER-2/neu Ki-67 P53 | ||
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