P53 abnormalities and outcomes in colorectal cancer: a systematic review

Munro, Alastair J.; Laı́n, Sonia; Lane, David P.

doi:10.1038/sj.bjc.6602358

Cited by 260 publications

(207 citation statements)

References 35 publications

(31 reference statements)

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“…These and other related markers have been extensively studied in recent years in primary colorectal cancers. 4,[22][23][24][25][26][27][28][29] The most frequent scenario, in which these markers were assessed has been stage II cancers to identify patients who might benefit from adjuvant therapy but would otherwise be denied of such an opportunity. 30 The data thus far have been inconclusive.…”

Section: Discussionmentioning

confidence: 99%

Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance

et al. 2011

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Folate receptor alpha (FRa), encoded by folate receptor 1 (adult) gene, has emerged as a cancer biomarker and potential therapeutic target. In addition, its expression in tumors may offer prognostic information. The aim of this study was to assess the prognostic value of FRa expression and other common molecular markers in resected liver metastases from colorectal cancer. To maximize potential biological differences, we selected two groups of patients with markedly different outcomes as study subjects. Immunohistochemical analysis of FRa expression and other common markers (thymidylate synthase, p53, p27, BCL2, ki67, MLH1, MSH2 and MGMT) on tissue microarrays was carried out on samples from 160 patients; 56 patients survived at least 10 years following liver resection, and 104 died within 2 years of surgery. These markers were evaluated and compared with standard clinical predictors of outcome including a previously validated clinical risk score. Our results showed that in addition to known clinical risk factors, FRa positivity was significantly associated with the early death group (32% compared with 13%; P ¼ 0.03). None of the other common molecular markers were differentially expressed between the two groups. On multivariate analysis, clinical risk score, margin status and FRa expression were independently associated with outcome. Specific multivariate comparisons confirmed that FRa expression was associated with outcome independent of the clinical risk score and margin. These data demonstrate that FRa expression is present in a subset of resected hepatic colorectal cancer metastases, and this marker is independently associated with survival after hepatic resection. The prognostic value of FRa expression and the utility of FRa-targeted therapies in stage-IV colorectal cancer patients deserve further exploration. Modern Pathology (2011) 24, 1221-1228; doi:10.1038/modpathol.2011.82; published online 13 May 2011Keywords: folate receptor 1 (adult); folate-targeted therapy; liver metastasisThe liver is the most common site of metastasis from colorectal carcinoma. Although 20 to 25% of colorectal carcinoma patients present with synchronous liver metastases, another 60% develop such metastases after the diagnosis of the primary tumor. 1,2 Surgical resection is potentially curative for colorectal cancer metastases confined to the liver, with a 5-year survival rate between 30 and 50%. 3 Some patients, however, recur early after resection and have a poor outcome. A clinical risk score developed by Fong et al 1 incorporates five preoperative criteria including nodal status of the primary lesion, disease-free interval, number of hepatic metastases, size of the largest metastasis and preoperative carcinoembryonic antigen (CEA) level. This

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Section: Discussionmentioning

confidence: 99%

Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance

et al. 2011

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“…Although p53 is recognized as an important factor for tumor suppression, its relationship with prognosis in cancer is controversial. Even large studies of TP53 gene in colorectal cancer have not been able to establish the relationship between TP53 gene mutation and prognosis [27,28].…”

Section: Discussionmentioning

confidence: 99%

Mortalin is a prognostic factor of gastric cancer with normal p53 function

et al. 2013

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Background Mortalin is a heat-non-inducible member of the heat shock protein 70 family. Mortalin binds to p53 and prevents p53 from entering the nucleus. To understand the significance of mortalin in gastric cancer, we investigated the expression of mortalin and p53. Methods Expression of mortalin and p53 was examined by immunohistochemical staining of 182 clinical samples of gastric cancer. Results Mortalin-positive and aberrant p53-positive tumors were found in 75.2 and 49.5 % of cases, respectively. Mortalin-positive tumors were deeper in invasion and had more lymph node and liver metastases compared with mortalin-negative tumors (P \ 0.01, P \ 0.05, respectively). Mortalin-positive tumors had worse prognosis compared with mortalin-negative tumors (P = 0.035). Moreover, in tumors with normal p53 function, mortalinpositive tumors had worse prognosis compared with mortalin-negative tumors (P = 0.017). Conclusions Mortalin has a great impact on gastric cancer with normal p53. Therefore, mortalin is a target molecule for treatment of gastric cancer, as well as a promising prognostic factor, especially in tumors with normal p53.

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“…Colorectal cancer is the other major tumor type to have received considerable attention in terms of the prognostic significance of p53 mutation. A recent systematic review identified 168 reports on p53 abnormality and outcome 58 , although many of these were based on the use of IHC. For studies that used mutation analysis, the increased risk of death associated with p53 mutation in the overall group was 1.31 (95% CI: 1.19-1.45) and even higher for patients classified as having good prognosis (RR ¼ 1.63, 95% CI: 1.40-1.90).…”

Section: Prognostic Significance Of P53 Mutation In Cancer -Does It Amentioning

confidence: 99%

p53 and disease: when the guardian angel fails

2006

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The p53 tumor suppressor gene (TP53) is mutated more often in human cancers than any other gene yet reported. Of importance, it is mutated frequently in the common human malignancies of the breast and colorectum and also, but less frequently, in other significant human cancers such as glioblastomas. There is also one inherited cancer predisposing syndrome called Li-Fraumeni that is caused by TP53 mutations. In this review, we discuss the significance of p53 mutations in some of the above tumors with a view to outlining how p53 contributes to malignant progression. We also discuss the usefulness of TP53 status as a prognostic marker and its role as a predictor of response to therapy. Finally, we outline some evidence that abnormalities in p53 function contribute to the etiology of other non-neoplastic diseases.

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P53 abnormalities and outcomes in colorectal cancer: a systematic review

Cited by 260 publications

References 35 publications

Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance

Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance

Mortalin is a prognostic factor of gastric cancer with normal p53 function

p53 and disease: when the guardian angel fails

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