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

Kakeji, Yoshihiro; Korenaga, Daisuke; Tsujitani, Shunichi; Baba, Hideo; Anai, Hideaki; Maehara, Yoshihiko; Sugimachi, Keizō

doi:10.1038/bjc.1993.108

Cited by 128 publications

(78 citation statements)

References 21 publications

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“…In some studies, the expression of p53 was associated with a higher frequency of serosal, vascular, and lymphatic invasion, increased lymph node metastases and, consequently, a more advanced tumour stage (Kakeji et al, 1993;Kim et al, 1997;Monig et al, 1997;Maehara et al, 1999). By contrast, other authors have not shown the association of p53 expression with node metastases or serosal invasion Maeda et al, 1998).…”

Section: Discussionmentioning

confidence: 91%

“…If 10% or more of the malignant nuclei were stained, the slide was scored as positive. If fewer than 10% of the nuclei were stained, the slide was scored as negative, in accordance with other authors (Kakeji et al, 1993;Maehara et al, 1999). All specimens were analysed by two separate investigators (CF and AV) who were blinded to all clinical information.…”

Section: Immunohistochemical Methodsmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 91%

Section: Immunohistochemical Methodsmentioning

confidence: 99%

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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“…More than half of human malignancies tested so far have been shown to overexpress the p53 protein (Bartek et al, 1991;Gusterson et al, 1991;Porter et al, 1992). There are reports of increasing immunostaining intensity with increasing progression of neoplasia in surgical samples (Allred et al, 1993;Bell et al, 1993;Kakeji et al, 1993).…”

Section: Function Of the P53mentioning

confidence: 99%

Tumourigenesis associated with the p53 tumour suppressor gene

Chang

Syrjänen²,

Tervahauta³

et al. 1993

Br J Cancer

111

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Summary The p53 gene is contained within 16-20 kb of cellular DNA located on the short arm of human chromosome 17 at position 17pl3.1. This gene encodes a 393-amino-acid nuclear phosphoprotein involved in the regulation of cell proliferation. Current evidence suggests that loss of normal p53 function is associated with cell transformation in vitro and development of neoplasms in vivo. More than 50% of human malignancies of epithelial, mesenchymal, haematopoietic, lymphoid, and central nervous system origin analysed thus far, were shown to contain an altered p53 gene. The oncoproteins derived from several tumour viruses, including the SV40 large T antigen, the adenovirus EIB protein and papillomavirus E6 protein, as well as specific cellular gene products, e.g. murine double minute-2 (MDM2), were found to bind to the wild-type p53 protein and presumably lead to inactivation of this gene product. Therefore, the inactivation of p53 tumour suppressor gene is currently regarded as an almost universal step in the development of human cancers. The current data on p53-associated tumourigenesis are briefly discussed in this minireview.

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“…(B) Survival time for p53-positive patients (n = 115) was shorter than for p53-negative patients (n = 138) in those in the node-positive group (P = 0.0060). Solid line, p53-negative patients; light line, p53-positive patients The p53 abnormal staining was reported to be related to the proliferating activity of cancer cells (Kakeji et al, 1993), and aggressive behaviour of cancer cells for serosal invasion, lymph node metastasis of gastric cancer and a poorer prognosis ensued (Martin et al, 1992;Starzynska et al, 1992;Joypaul et al, 1994;Maehara et al, 1995;Mšnig et al, 1997). Because vascular and lymphatic involvement are closely related to p53 expression, p53 expression was closely related to tumour invasion and metastasis and, in particular, proved to be a significant prognostic factor for node-positive cases.…”

Section: Figurementioning

confidence: 99%

“…A distinct nuclear immunoreaction for p53 was recorded as positive, and here the nuclear staining pattern was diffuse with little variation. When 10% of the cancer cells showed a positive nuclear staining, a positive-staining was defined (Kakeji et al, 1993).…”

Section: P53 Stainingmentioning

confidence: 99%

Prognostic value of p53 protein expression for patients with gastric cancer – a multivariate analysis

et al. 1999

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Mutations in the p53 gene, one of the most common genetic alterations in human cancer, are implicated in tumorigenesis and tumour progression. Although p53 protein expression appears to be correlated to prognosis in patients with malignancy, its prognostic role in gastric cancer has remained controversial. We examined the clinical significance of p53 overexpression in 427 patients with gastric cancer, using multivariate analysis. Tumour sections of gastric cancer tissues from these 427 Japanese patients were stained immunohistochemically with monoclonal antibody PAb1801. The presence of p53 expression was statistically compared with clinicopathological features and post-operative survival, using univariate and multivariate analyses. p53 expression was detected in 38.6% (165 out of 427) of these gastric cancers and immunoreactivity was not observed in normal mucosa adjacent to the tumour. A higher rate of p53 detection was observed among large tumours and in those with a prominent depth of invasion, lymphatic and vascular invasion and lymph node involvement. Prognosis was significantly worse for patients with p53-positive-staining tumours. The 5-year survival rate was 62.5% for patients with p53-negative tumours and 43.3% for those with positive malignancies. p53 expression was a significant prognostic factor for node-positive gastric cancers in subjects undergoing treatment with curative resection, as assessed by Cox regression analysis. Thus, the expression of p53 was closely related to the potential for tumour advance and a poorer post-operative prognosis for patients with gastric cancer. © 1999 Cancer Research Campaign

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

Cited by 128 publications

References 21 publications

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

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

Tumourigenesis associated with the p53 tumour suppressor gene

Prognostic value of p53 protein expression for patients with gastric cancer – a multivariate analysis

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