Prognostic Significance of p53 and Ki67 Proteins Expression in Greek Gastric Cancer Patients

Abstract Aim: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. Materials and methods: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. Results: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival. Conclusions: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.

[1]  Ph.D. Ulf H. Haglund M.D.,et al.  Current management of gastric cancer , 2007, Journal of Gastrointestinal Surgery.

[2]  S. Takao,et al.  Comparison of p53 expression in proximal and distal gastric cancer: Histopathologic correlation and prognostic significance , 1997, Annals of Surgical Oncology.

[3]  I. Burney,et al.  The prognostic significance of p53, p27kip1, p21waf1, HER‐2/neu, and Ki67 proteins expression in gastric cancer: A clinicopathological and immunohistochemical study of 121 Arab patients , 2005, Journal of surgical oncology.

[4]  C. Oshima,et al.  Ki-67 as a prognostic marker in colorectal cancer but not in gastric cancer. , 2005, Neoplasma.

[5]  C. Cass,et al.  Gastric Cancer: Establishing Predictors of Biologic Behavior with Use of Population-Based Data , 2004, Annals of Surgical Oncology.

[6]  E. Cook,et al.  Asian ethnicity-related differences in gastric cancer presentation and outcome among patients treated at a canadian cancer center. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  K. Choe,et al.  Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. , 2003, Japanese journal of clinical oncology.

[8]  C. Fenoglio-Preiser,et al.  TP53 and gastric carcinoma: A review , 2003, Human mutation.

[9]  L. David,et al.  Clinicopathologic Profiles and Prognosis of Gastric Carcinomas from the Cardia, Fundus/Body and Antrum , 2001, Digestive Surgery.

[10]  K. Becker,et al.  Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxirubicin, and cisplatinum , 2001, Cancer.

[11]  M. Medrano,et al.  P53 protein expression in gastric adenocarcinoma. Negative predictor of survival after postoperative adjuvant chemotherapy. , 2000, Anticancer research.

[12]  S. Steinberg,et al.  Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-ErbB2, c-myc and EGFr as prognostic factors in gastric cancer. , 2000, Histology and histopathology.

[13]  H. Cho,et al.  DNA ploidy patterns in gastric adenocarcinoma. , 2000, Journal of Korean medical science.

[14]  J. Nesland,et al.  The prognostic value of p53 and c‐erb b‐2 immunostaining is overrated for patients with lymph node negative breast carcinoma , 2000, Cancer.

[15]  S. Isaacs,et al.  Expression of p53 and p21waf1/cip1 in gastric carcinoma: lack of inter-relationship or correlation with prognosis. , 2000, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[16]  F. Roviello,et al.  p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type , 1999, Annals of Surgical Oncology.

[17]  M. Terashima,et al.  Evaluation of the ratio of lymph node metastasis as a prognostic factor in patients with gastric cancer , 1999, Gastric Cancer.

[18]  N. Hashimoto,et al.  Expression of p53 and RB Proteins in Squamous Cell Carcinoma of the Esophagus: Their Relationship With Clinicopathologic Characteristics , 1999, Annals of Surgical Oncology.

[19]  E. Tokunaga,et al.  Prognostic value of p53 protein expression for patients with gastric cancer – a multivariate analysis , 1999, British Journal of Cancer.

[20]  Y. Kakeji,et al.  Clinical implications of serum anti‐p53 antibodies for patients with gastric carcinoma , 1999, Cancer.

[21]  J. Siewert,et al.  The current management of gastric cancer. , 1999, Advances in surgery.

[22]  D. Lane,et al.  The p53 tumour suppressor gene , 1998, The British journal of surgery.

[23]  S. Cascinu,et al.  Expression of p53 protein and resistance to preoperative chemotherapy in locally advanced gastric carcinoma , 1998, Cancer.

[24]  M. Ikeguchi,et al.  The correlation between the expression of p53 protein and DNA ploidy in patients with gastric cancer that has invaded the serosa. , 1997, Anticancer research.

[25]  A. Ochiai,et al.  c-erbB2 and p53 expression are not associated with stage progression of gastric cancer in Britain or Japan. , 1997, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[26]  S. Nordling,et al.  Ki-67, ploidy and S-phase fraction as prognostic factors in gastric cancer. , 1997, Anticancer research.

[27]  S. Tsujitani,et al.  Expression of p21 (waf1/cip1/sdi1), but not p53 protein, is a factor in the survival of patients with advanced gastric carcinoma , 1997, Cancer.

[28]  F. Seow-Choen,et al.  Mutant plasma p53 protein levels: Prognostication in colorectal carcinoma , 1997, The British journal of surgery.

[29]  D. Shin,et al.  Relationship between p53 overexpression and gastric cancer progression. , 1997, Oncology.

[30]  B. Iacopetta,et al.  p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma , 1996, International journal of cancer.

[31]  P. Hamilton,et al.  Colorectal cell kinetics , 1996, The British journal of surgery.

[32]  S. Nordling,et al.  Ki-67 immunoreactivity, ploidy and S-phase fraction as prognostic factors in patients with gastric carcinoma. , 1996, Oncology.

[33]  F. Borchard,et al.  PROGNOSTIC INFLUENCE OF p53 EXPRESSION IN GASTRIC CANCER , 1996, The Journal of pathology.

[34]  Y. Chung,et al.  Tumour angiogenesis and tumour cell proliferation as prognostic indicators in gastric carcinoma. , 1995, British Journal of Cancer.

[35]  Y. Maehara,et al.  The prognostic significance of proliferating cell nuclear antigen in clinical gastric cancer. , 1993, Surgery.

[36]  K. Gatter,et al.  Monoclonal antibody Ki‐67: its use in histopathology , 1990, Histopathology.

[37]  I. Ninomiya,et al.  Growth fractions in gastric carcinomas determined with monoclonal antibody Ki‐67 , 1990, Cancer.

[38]  S. Ming Gastric carcinoma: A pathobiological classification , 1977 .

[39]  P. Laurén,et al.  THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. , 1965, Acta pathologica et microbiologica Scandinavica.