The TP53 Colorectal Cancer International Collaborative Study on the Prognostic and Predictive Significance of <i>p53</i> Mutation: Influence of Tumor Site, Type of Mutation, and Adjuvant Treatment

Russo, Antonio; Bazan, Viviana; Iacopetta, Barry; Kerr, David; Soussi, Thierry; Gebbia, Nicola

doi:10.1200/jco.2005.00.471

Cited by 341 publications

(281 citation statements)

References 45 publications

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“…The TP53 gene is one of the most frequently mutated genes in human cancers 4, 5, 23, 24. Approximately half of all cancers have mutated TP53 4, 5.…”

Section: Discussionmentioning

confidence: 99%

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Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

Takahashi

Sugai

Habano

et al. 2016

Intl Journal of Cancer

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Differences in the pathogenesis of microsatellite stable (MSS) sporadic colorectal cancers (CRCs) between left‐sided CRC (LC) and right‐sided CRC (RC) have not been clarified. To identify pathogenesis‐related genomic differences between MSS CRCs within the two locations, we performed a comprehensive molecular analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite instability (MSI; high and low/negative) and DNA methylation status (low methylation epigenome; intermediate methylation epigenome [IME] or high methylation epigenome [HME]) were determined using polymerase chain reaction (PCR) microsatellite analysis and PCR‐bisulfite pyrosequencing, respectively. Additionally, mutations in the TP53, KRAS, BRAF and PIK3CA genes were examined using PCR‐bisulfite pyrosequencing (for KRAS and BRAF mutations) or PCR‐single conformation polymorphism (for TP53 and PIK3CA mutations), followed by sequencing of aberrant bands. Finally, a genome‐wide study using a copy number alteration (CNA)‐targeted single nucleotide polymorphism array was performed. Ninety‐two CRCs were classified into 71 MSS and 21 MSI phenotypes. We examined 71 CRCs with the MSS phenotype (LC, 56; RC, 15). Mutations in KRAS were associated with RC with the MSS phenotype, whereas mutations in TP53 were more frequently found in LC with the MSS phenotype. There were significant differences in the frequencies of KRAS and TP53 mutations in the IME between LC and RC with the MSS phenotype. Although CNA gains were associated with LC with the MSS phenotype, CNA losses were not major alterations associated with the MSS phenotype. These findings suggested that the molecular pathogenesis of the MSS phenotype in LC was different from that in RC.

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“…The TP53 gene is one of the most frequently mutated genes in human cancers 4, 5, 23, 24. Approximately half of all cancers have mutated TP53 4, 5.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, mutation of the TP53 gene is found in 60–80% of CRCs 4, 5, 7. Mutation of the TP53 gene is a representative event during the progression of CRC 4, 5, 23, 24. Recent studies have shown that mutation of TP53 is observed more frequently in LC than in RC 9, 25.…”

Section: Discussionmentioning

confidence: 99%

Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

Takahashi

Sugai

Habano

et al. 2016

Intl Journal of Cancer

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“…This low rate is in keeping with the literature, indicating a significantly lower frequency of microsatellite instability-high phenotype in advanced colorectal cancers when compared with primary cancers, and likely reflecting the fact that microsatellite instable cancers are less likely to metastasize. 28 The low number of positive cases in our series makes it impossible to draw any meaningful conclusion about its prognostic significance in patients with resected colorectal cancer liver metastases. Thymidylate synthase has been studied in resected colorectal cancer liver metastases with mixed results.…”

Section: Discussionmentioning

confidence: 77%

“…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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“…The carcinogenic pathway in colorectal cancers is characterized by allelic losses on chromosome 5q (APC), 7p (p53), and 18q (DCC/SMAD4) and is therefore called the chromosomal instability (CNI) pathway. Patients with CRC involving a p53 mutation have worse survival than do patients whose cancers do not have a p53 mutation [22].…”

Section: Discussionmentioning

confidence: 99%

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

Shinada

Tsukiyama

Sho

et al. 2011

Biochemical and Biophysical Research Communications

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The ubiquitin-proteasomal system plays a crucial role in oncogenesis in colorectal tissues. Recent studies have shown that stability of -catenin, which functions as an oncogene for colorectal cancer, is regulated by ubiquitin-mediated degradation. It has been reported that a putative E3 ubiquitin ligase, RNF43, is highly expressed in human colorectal carcinoma and that RNF43 promotes cell growth. However, the involvement of RNF43 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that RNF43 binds to NEDD-4-like ubiquitin-protein ligase-1 (NEDL1), which enhances pro-apoptotic activity by p53. In addition, we found that RNF43 also interacts with p53 and that RNF43 suppresses transcriptional activity of p53 in H1299 cells and attenuates apoptosis induced by ultraviolet irradiation. These findings suggest that RNF43 is associated with p53-mediated apoptosis in collaboration with NEDL1 in colorectal carcinogenesis.3

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The TP53 Colorectal Cancer International Collaborative Study on the Prognostic and Predictive Significance of p53 Mutation: Influence of Tumor Site, Type of Mutation, and Adjuvant Treatment

Abstract: Analysis of TP53 mutations from a large cohort of CRC patients has identified tumor site, type of mutation, and adjuvant treatment as important factors in determining the prognostic significance of this genetic alteration.

Cited by 341 publications

References 45 publications

Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

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

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

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