Prognostic significance of Bcl-2 and p53 expression in gastric cancer
- 127 Downloads
Background and aims
Apoptosis regulates cell death and influences cell proliferation and therefore may play an important role in development or growth of various malignant tumors. The Bcl-2 and p53 are closely linked in the regulation of apoptosis. We investigated the prognostic significance of Bcl-2 and p53 expression in patients with gastric cancer.
Patients and methods
Immunohistochemistry was used to study Bcl-2 and p53 expression in 308 consecutive patients with gastric cancer.
Bcl-2 expression was positive in 39 patients (12.7%) and showed a significant negative correlation with depth of invasion and lymph node metastasis. p53 expression was observed in 105 patients (34.1%) and was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and intestinal type. Patients with Bcl-2+ tumors showed a trend to better 5-year survival rate (81%) than those with Bcl-2− negative tumors (71%). The 5-year survival rate in p53 positive cases (60%) was significantly lower than that in p53-negative cases (78%). In addition, p53 expression showed a significantly poorer prognosis in both diffuse and intestinal types. In multivariate analysis restricted to patients with R0 resection p53 expression was an independent prognostic factor (relative risk: 2.063). In combined assessment of p53 and Bcl-2 expression the group with p53+/Bcl-2− tumors showed significantly worse 5-year survival (57%) than the other groups, while best survival was seen in the group with p53+/Bcl-2+ tumors (100%).
p53 expression is an unfavorable prognostic factor in gastric cancer. Bcl-2 expression may have possible prognostic value when combined with p53 expression.
KeywordsBcl-2 p53 Gastric cancer
This study was supported by the Korean Foundation for Cancer Research Grant No. 20-12-4.
- 2.Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M (1991) Wild-type p53 induces apoptosis of myeloid leukemic cells that is inhibited by interleutin-6. Nature 353:345–347Google Scholar
- 3.Fukuhara S, Rowley JD, Variakojis D, Golomb HM (1979) Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. Cancer Res 39:3119–3128Google Scholar
- 5.Cleary ML, Sklar J (1985) Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a chromosome 18. Proc Natl Acad Sci USA 82:7437–7443Google Scholar
- 11.Nakanishi H, Ohsawa M, Naka N, Uchida A, Ochi T, Aozasa K (1997) Immunohistochemical detection of bcl-2 and p53 proteins and apoptosis in soft tissue sarcoma: their correlations with prognosis. Oncology 54:238–244Google Scholar
- 13.Pollina L, Pacini F, Fontanini G, Vignati S, Bevilacqua G, Basolo F (1996) bcl-2, p53 and proliferating cell nuclear antigen expression is related to the degree of differentiation in thyroid carcinomas. Br J Cancer 73:139–143Google Scholar
- 23.McLaren R, Kuzu I, Dunnill M, Harris A, Lane D, Gatter KC (1992) The relationship of p53 immuostaining to survival in carcinoma of the lung. Br J Cancer 66:735–738Google Scholar
- 25.Seshadri R, Leong ASY, McCaul K, Firgaira FA, Setlur V, Horsfall DJ (1996) Relationship between p53 gene abnormalities and other tumour characteristics in breast cancer prognosis. Int J Cancer 69:135–141Google Scholar
- 27.Martin HM, Filipe MI, Morris RW, Lane DP, Silvestre F (1992) p53 expression and prognosis in gastric carcinoma. Int J Cancer 50:859–862Google Scholar
- 29.Aizawa K, Ueki K, Suzuki S, Yabusaki H, Kanda T, Nishimaki T, Suzuki T, Hatakeyama K (1999) Apoptosis and Bcl-2 expression in gastric carcinoma: correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis. Int J Oncol 14:85–91Google Scholar
- 33.Henriksen R, Wilander E, Oberg K (1995) Expression and prognostic significance of Bcl-2 in ovarian tumours. Br J Cancer 72:1324–1329Google Scholar
- 34.Inada T, Kikuyama S, Ichikawa A, Igarashi S, Ogata Y (1998) Bcl-2 expression as a prognostic factor of survival of gastric carcinoma. Anticaner Res 18:2003–2010Google Scholar
- 37.van Slooten HJ, Clahsen PC, van Dierendonck JH, Duval C, Pallud C, Mandard AM, Delobelle-Deroide A, van de Velde CJ, van de Vijver MJ (1996) Expression of bcl-2 in node-negative breast cancer is associated with various prognostic factors, but does not predict response to one course of perioperative chemotherapy. Br J Cancer 74:78–85Google Scholar
- 38.Diebold J, Baretton G, Felchner M, Meier W, Dopfer K, Schmidt M, Lohrs U (1995) Bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas. Am J Clin Pathol 105:341–349Google Scholar
- 45.Joypaul BV, Hopwood D, Newman EL, Qureshi S, Grant A, Ogston SA, Lane DP, Cuschieri A (1994) The prognostic significance of the accumulation of p53 tumor-suppressor gene protein in gastric adenocarcinoma. Br J Cancer 68:943–946Google Scholar
- 46.Maehara Y, Okuyama T, Kakeji Y, Endo K, Yamamoto M, Sugimachi K (1995) A tumor-associated cell-surface glycoprotein accompanying p53 overexpression and higher growth potential for gastric cancer. Br J Cancer 71:999–1002Google Scholar
- 48.Maehara Y, Tomoda M, Hasuda S, Kabashima A, Tokunaga E, Kakeji Y, Sugimachi K (1999) Prognostic value of p53 protein expression for patients with gastric cancer-multivariate analysis. Br J Cancer 79:1255–1261Google Scholar
- 51.Shiao YH, Palli D, Buzard GS, Caporaso NE, Amorosi A, Saieva C, Fraumeni JF Jr, Anderson LM, Rice JM (1998) Implications of p53 mutation spectrum for cancer etiology in gastric cancers of various histologic types from a high-risk area of central Italy. Carcinogenesis 19:2145–2149CrossRefPubMedGoogle Scholar
- 55.Watson AJ, Merritt AJ, Jones LS, Askew JN, Anderson E, Becciolini A, Balzi M, Potten CS, Hickman JA (1996) Evidence of reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas. Br J Cancer 73:889–895Google Scholar