Expression of p53 and p21waf1/cip1in gastric carcinoma: lack of inter-relationship or correlation with prognosis

doi:10.1053/ejso.1999.0738

European Journal of Surgical Oncology (EJSO)

Volume 26, Issue 1, February 2000, Pages 39-43

https://doi.org/10.1053/ejso.1999.0738 Get rights and content

Abstract

Aims: The cell cycle regulators p53 and p21^waf1/cip1are expressed variably in human cancers. We investigated their expression in gastric carcinoma and determined their inter-relationship and prognostic significance. Methods: Immunohistochemistry was used to determine their expression in material from 100 resected specimens of gastric carcinoma, and comparison was then made of the degree of expression between each, with conventional clinicopathological indices and with survival. Results: Positivity was found with p53 (40%) and p21 (75%). There was no significant correlation between the expression of each individual marker, nor between each marker and 5-year survival. There appeared to be an association between p53 expression and lymph node metastases, and a higher frequency of p21^waf1/cip1expression in males. Conclusions: The expression of p53 and p21^waf1/cip1as detected by immunohistochemistry were of no value in predicting the prognosis of patients with gastric carcinoma.

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Cited by (22)

Oncogenic functions of tumour suppressor p21<sup>Waf1/Cip1/Sdi1</sup>: Association with cell senescence and tumour-promoting activities of stromal fibroblasts
2002, Cancer Letters
p21^{Waf1/Cip1/Sdi1} is best known as a broad-specificity inhibitor of cyclin/cyclin-dependent kinase complexes, but p21 also interacts with many other regulators of transcription or signal transduction. p21 induction, which is mediated by p53 and by p53-independent mechanisms, is essential for the onset of cell cycle arrest in damage response and cell senescence. The effects of p21 knockout in mice and its expression patterns in human cancer are consistent with a role for p21 as both a tumour suppressor and an oncogene. Several functions of p21 are likely to promote carcinogenesis and tumour progression. These include endoreduplication and abnormal mitosis that develop in tumour cells after release from p21-induced growth arrest, the ability of p21 to inhibit apoptosis through several different mechanisms, and its ability to stimulate transcription of secreted factors with mitogenic and anti-apoptotic activities. The latter effects of p21 show close resemblance to paracrine activities of senescent cells and to tumour-promoting functions of stromal fibroblasts. Therapeutic strategies targeting the oncogenic consequences of p21 expression may provide a new approach to chemoprevention and treatment of cancer.
Expression of p21<sup>WAF1/CIP1</sup> and p53 proteins in gastric carcinoma: Its relationships with cell proliferation activity and prognosis
2001, Cancer Letters
The expressions of p21^WAF1/CIP1, p53 proteins, and Ki-67 antigen were investigated immunohistochemically in 190 primary gastric carcinomas. Of the 190 tumors, 40.5% positively expressed p21^WAF1/CIP1 and 42.1% positively expressed p53. The expression of p21^WAF1/CIP1 was significantly associated with clinicopathological factors including gender, tumor size, status of lymph node, and clinicopathological stage (P<0.05 for all), but p21^WAF1/CIP1 expression showed no clear correlation with Ki-67 labeling index. The mean Ki-67 labeling index was significantly higher in p53-positive cases than p53-negative cases (P<0.0001). However, among the clinicopathological factors examined, expression of p53 correlated only with age. Univariate and multivariate survival analyses revealed that clinicopathological stage (P<0.001) and expression status of p21^WAF1/CIP1 (P<0.05) were independent prognostic factors. Neither the expression status of p53 nor the Ki-67 labeling index, however, influenced the prognosis of patients with gastric cancer.
Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis
2001, Experimental and Toxicologic Pathology
Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and β-catenin by immunohistochemistry and for methylation of the CDH1 promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDH1 promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of β-catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer.
Absence of CIP1/KIP1 hypermethylation in gastric cancer patients from Northern Brazil
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Genetic polymorphisms of p21 and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck
2010, Carcinogenesis
The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients
2010, Romanian Journal of Morphology and Embryology

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^f1: Correspondence to: P. V. Kaye, Department of Histopathology, Kings Mill Centre for Health Care Services, Mansfield Road, Sutton-in-Ashfield, Notts NG17 4JL UK. Fax: +44 1623 626 575, E-mail: [email protected]

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Original ArticleExpression of p53 and p21waf1/cip1in gastric carcinoma: lack of inter-relationship or correlation with prognosis

Abstract

Eur J Cancer

Hum Pathol

Pathology and prognosis of gastric carcinoma

Cancer

Tumorigenesis associated with the p53 tumour suppressor gene

Br J Cancer

Cell-cycle control and its watchman

Nature

The p53 tumour suppressor gene

Nature

An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms

J Pathol

p53 in tumour pathology: can we trust immunohistochemistry?—revisited

J Pathol

Relationship between abnormal p53 protein and failure to express p21 protein in human breast carcinomas

J Pathol

p21WAF1immunohistochemical expression in breast carcinoma: correlations with clinicopathological data, oestrogen receptor status, MIB1 expression, p53 gene and protein alterations and relapse-free survival

Br J Cancer

p21(Waf1/Cip1) and p53 protein expression in breast cancer

Am J Clin Pathol

p53 expression and prognosis in gastric carcinoma

Int J Cancer

Gastric cancer with p53 overexpression has high potential for metastasizing to lymph nodes

Br J Cancer

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

Br J Cancer

Original Article
Expression of p53 and p21^waf1/cip1in gastric carcinoma: lack of inter-relationship or correlation with prognosis

p21^WAF1immunohistochemical expression in breast carcinoma: correlations with clinicopathological data, oestrogen receptor status, MIB1 expression, p53 gene and protein alterations and relapse-free survival