BRAFV600E Mutation and Its Association with Clinicopathological Features of Colorectal Cancer: A Systematic Review and Meta-Analysis

Chen, Dong; Huang, Junlan; Li, Kai; Zhang, Liqun; Yang, Zhao; Chuai, Zheng-Ran; Wang, Yunxia; Shi, Dachuan; Huang, Qing; Fu, Weiling

doi:10.1371/journal.pone.0090607

Cited by 134 publications

(117 citation statements)

References 39 publications

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“…There is a link between BRAF V600E status and worse prognosis (36,37) and BRAF V600E and more advanced cancer, being mostly present in right-sided tumours (38,39). As discussed before, BRAF V600E has been found to interfere with KRAS occasionally.…”

Section: Discussionmentioning

confidence: 83%

KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer

Sideris

Moorhead

Díaz‐Cano

et al. 2016

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Abstract. Background The method of local excision, that has recently, gained wider acceptance, in early rectal cancer, is transanal endoscopic microsurgery (TEMS). TEMS generally offers advantages in operative access and oncological clearance over transanal resection (TAR), but recently a number of similar logic techniques with various rectal ports for endoscopic excision of rectal tumours has been invented. Those methods are collectively named transanal minimal-invasive surgery (TAMIS) and for oncological purposes they share the same features of local excision as TEMS (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).TEMS is a minimally invasive technique that was introduced by Buess in the early 1980's (2). Through the new rectoscope with 3D binocular optic and the endoscopic instruments, it offers better access to proximal lesions with lower margin positivity and fragmentation and magnification of the operative field (2, 15). TEMS is a safe procedure that offers low complication rates and peri-operative morbidity (10.7%) (4). There have been multiple studies to suggest that TEMS is the operation of choice for rectal adenomas (1), retrorectal and submucosal rectal lesions (5). Furthermore, TEMS offers the advantage of not damaging the anorectal function (7).TEMS is indicated as a curative treatment for malignant neoplasms that are histologically confirmed as pT1 sm1 carcinomas, whereas T1 sm2-3 and T2 lesions are still under question (8). A number of studies have shown that TEMS can have comparable results with radical surgery (1,8,12,16) for rectal cancer.There has been concern about oncologic outcomes following TEMS (17). Some studies support that there is potentially a higher risk of local recurrence rate with TEMS (8,10,18). Efforts have been made to classify risk with morphological and histological criteria with better patients' selection (1, 6-9); however, the risk stratification remains 5315

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Section: Discussionmentioning

confidence: 83%

KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer

Sideris

Moorhead

Díaz‐Cano

et al. 2016

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“…When studying the second tertile, this observation was confirmed (P ¼ 0.0071; HR, 2.7; 95% CI, 1.28-5.78; Table 3). The presence of BRAF-V600E mutation is known to be strongly correlated with a decrease in patient survival (27). To avoid the influence of BRAF V600E mutation poor prognosis on OS analysis, we also analyzed this parameter exclusively in KRAS-mutant mCRC patients (N ¼ 38).…”

Section: Os Analysis In the Mutant Cohortmentioning

confidence: 99%

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

147

108

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Purpose: Circulating cell-free DNA (ccfDNA) is a valuable source of tumor material obtained from a simple blood sampling that enables noninvasive analysis of the tumor genome. Our goal was to carry out a multiparametric analysis of ccfDNA and evaluate its prognostic value by investigating the overall survival (OS) of 97 metastatic colorectal cancer patients (mCRC).Experimental Design: Qualitative parameters (determination of the main KRAS exon2 and BRAF V600E mutations) and quantitative parameters (total ccfDNA concentration, mutant ccfDNA concentration, the proportion of mutant ccfDNA, and ccfDNA integrity index) were determined simultaneously in a single run using a unique Q-PCR multimarker approach (100% success rate).Results: The median follow-up time was 36 months and median OS was 22 months. Patients showing high ccfDNA levels had significantly shorter OS (18.07 months vs. 28.5 months, P ¼ 0.0087). Moreover, multivariate analysis revealed that a high ccfDNA level is an independent prognostic factor (P ¼ 0.034). All ccfDNA parameters were of prognostic interest: patients with higher levels of mutant ccfDNA and higher mutation loads for the detected mutations had shorter OS (P ¼ 0.0089 and P ¼ 0.05, respectively). In addition, the level of ccfDNA fragmentation correlated positively with decreased OS in the exclusive KRAS/ BRAF-mutant cohort of patients (P ¼ 0.0052) and appeared as a strong independent prognostic factor (P ¼ 0.0072), whereas it was not significant in the exclusive KRAS/BRAF WT cohort of patients (P ¼ 0.67).Conclusions: Our data provide for the first time qualitative and quantitative evidence in favor of multiparametric ccfDNA analysis in mCRC patients for prognostic assessment.

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“…They are frequently associated with poor differentiation, mucinous histology, and advanced tumornode-metastasis stage (3). In patients with microsatellite-stable colorectal carcinoma (4,5) and those with advanced colorectal carcinoma (6), BRAF V600E mutation confers worse survival compared with their wild-type counterpart.…”

Section: Introductionmentioning

confidence: 99%

Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing

Estrella

Tetzlaff

Bassett

et al. 2015

Molecular Cancer Therapeutics

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Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in !20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (<20% of tumor cells) staining. Among 33 BRAF wildtype colorectal carcinomas, 16 (48%) had no or weak staining, whereas 15 (45%) had heterogeneous staining. In contrast with colorectal carcinoma, Bond and Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management.

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BRAFV600E Mutation and Its Association with Clinicopathological Features of Colorectal Cancer: A Systematic Review and Meta-Analysis

Cited by 134 publications

References 39 publications

KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer

KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing

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