The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma

Joypaul, B. V.; Hopwood, David A.; Newman, E. L.; Qureshi, S.; Grant, A.; Ogston, Simon; Lane, David P.; Cuschieri, Alfred

doi:10.1038/bjc.1994.182

Cited by 91 publications

(46 citation statements)

References 35 publications

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“…Other investigators have also shown that p21 loss correlates positively with the depth of cancer invasion and also stage progression in primary prostate cancer (Gao et al, 1995). Similar abnormalities have been reported in studies of other cell cycle-regulating factors such as p53 (Joypaul et al, 1994), Rb (Constancia et al, 1994), cyclins (Tahara E, 1994) and PCNA (Maeda et al, 1994). Our study and others suggest that cell cycle deregulation is an important factor in gastric cancer progression.…”

Section: Resultssupporting

confidence: 90%

“…Thus, it is reasonable to investigate the involvement of p53 function in cell cycle regulation by examining p21 protein expression. The p53 gene is an important tumour suppressor, and the correlation between its overexpression and tumour progression has been shown in gastric carcinoma (Martin et al, 1992;Joypaul et al, 1994;Gabbert et al, 1995 Cancer, 1981) were used for the clinicopathological classification, with one exception: tumours were divided into two histological subgroups -a differentiated type, which consisted of papillary and tubular adenocarcinomas, and an undifferentiated type, which included poorly differentiated adenocarcinoma, signet ring cell carcinoma and mucinous adenocarcinoma. All patients underwent gastrectomy.…”

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confidence: 99%

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Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma

Ogawa

Maeda²,

Onoda³

et al. 1997

Br J Cancer

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Summary Previous studies have shown that tumour-suppressor genes play an important role in the progression of solid tumours. Recently, the p21 WAF1/C1P1 tumour-suppressor protein has been reported to work as a critical downstream effector of p53 and a potent inhibitor of cyclindependent kinases. Thus, the p21WAF1/cIPl gene is thought to play a central role in tumour suppression. In this study we investigated p21 protein expression in gastric carcinomas. A total of 172 primary gastric carcinoma specimens were immunohistochemically stained for p21 protein expression. Correlations between p21 expression and clinicopathological features were examined. Loss of p21 expression was observed in 104 of 172 tumour tissues (60.4%), and the frequency of p21 loss increased as the stage progressed. Expression of p21 in the primary tumour was frequently lost in patients with either lymph node, liver or peritoneal metastases as compared with patients without metastases. In patients with p21-negative tumours, the risk of recurrence following curative surgery was significantly higher, and the prognosis was significantly poorer than in patients with p21-positive tumours. Loss of p21 expression in primary gastric carcinoma correlates with disease progression. The status of p21 gene expression may have prognostic value in this disease.

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Section: Resultssupporting

confidence: 90%

mentioning

confidence: 99%

Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma

Ogawa

Maeda²,

Onoda³

et al. 1997

Br J Cancer

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“…p53 expression was detected in 46% of patients, which falls within the range (40 -60%) of previously published gastric cancer series (Joypaul et al, 1994;Gabbert et al, 1995;Victorzon et al, 1996). Use of the immunohistochemical detection of p53 as a prognostic marker has yielded conflicting results (Fenoglio-Preiser et al, 2003).…”

Section: Discussionsupporting

confidence: 50%

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

et al. 2004

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This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n ¼ 53) or surgery plus adjuvant chemotherapy (n ¼ 103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P ¼ 0.005) and VEGF (P ¼ 0.005) expression were observed. Both MVD X100 (P ¼ 0.05) and positive VEGF expression (Po0.02) were associated with shorter disease-free survival, and positive VEGF expression (P ¼ 0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (Po0.0005 and 0.02, respectively) and overall survival (Po0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P ¼ 0.01).This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.

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“…The loss of p53 function is related to the progression of the tumor by allowing cells with damaged DNA to continue to multiply (23). In some studies, p53 expression in stomach cancer has been reported to be bad prognosis (9)(10)(11)(12)(13)(14), but other reports have shown that p53 expression has no effect on clinical results (24)(25)(26). The reasons for these conflicting results are unclear.…”

Section: Discussion Discussionmentioning

confidence: 43%

“…Mutation in the p53 gene is one of the most common genetic lesions associated with gastric cancer, and some studies have reported that the expression of p 53 is related to bad prognosis (9)(10)(11)(12)(13)(14).…”

Section: Introduction Introductionmentioning

confidence: 99%

A Pilot Multicenter Study Evaluating the Expression of p53 and ki-67 in Gastric Tumors and Their Utility for Guiding Treatment Strategy

Baek¹,

Kim²,

Kim³

et al. 2017

SGO

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Background: p53 mutation is the most common genetic alteration in cancers and influences clinical progression. Ki-67 protein is a cellular marker for proliferation in cancer or premalignant lesion. The aim of this study is to investigate whether p53 and Ki-67 measurements in gastric tumors would be helpful in determining treatment strategy. Methods: Immunohistochemical staining using monoclonal antibodies to p53 and Ki-67 was performed on specimens from 29 gastric adenomas (GA) by endoscopic submucosal dissection (ESD) and 240 gastric cancers (GC) by ESD or gastrectomy. Tumor cells with nuclear p53 and Ki-67 protein expression were arbitrarily graded into four groups: < 10 % = negative, 10-30 % = 1+, 30-60 % = 2+, and > 60 % = 3+. Results: The mean tumor sizes in the GA and GC groups were 17.3 ± 11.4 mm and 32.0 ± 20.9 mm respectively (P < 0.001). p53 positivity was not different between the GA and GC groups (P = 0.149), but Ki-67 positivity was significantly different between the 2 groups (P = 0.001). In addition, Ki-67 positivity tended to be increased as the pathologic progression changed from adenoma to cancer. Conclusions: Ki-67 positivity grade seems to be correlated with malignancy potential. Even if endoscopic biopsy showed low grade dysplasia, in lesions with high Ki-67 positivity, it is better to consider active ESD rather than just long-term follow up.

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The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma

Cited by 91 publications

References 35 publications

Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma

Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

A Pilot Multicenter Study Evaluating the Expression of p53 and ki-67 in Gastric Tumors and Their Utility for Guiding Treatment Strategy

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