Clinicopathologic study of 85 colorectal serrated adenocarcinomas: further insights into the full recognition of a new subset of colorectal carcinoma

García‐Solano, José; Pérez‐Guillermo, Miguel; Conesa‐Zamora, Pablo; Acosta-Ortega, Jesús; Trujillo‐Santos, Javier; Cerezuela-Fuentes, Pablo; Mäkinen, Markus J.

doi:10.1016/j.humpath.2010.04.002

Cited by 91 publications

(143 citation statements)

References 17 publications

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“…Furthermore, explorative analyses within the chemo‐naïve stage I–III subgroup suggest that CDX2 carries prognostic information for cancers with BRAF mutations, within both the MSI and MSS subtypes separately, highlighting CDX2 as a potential biomarker with additional prognostic information to MSI and BRAF status. This finding is in line with recent studies reporting synergistic oncogenic activity between loss of CDX2 and BRAF mutation in serrated tumors (Sakamoto et al ., 2017; Tong et al ., 2017), which is associated with more aggressive disease and a poor prognosis (Garcia‐Solano et al ., 2010). …”

Section: Discussionmentioning

confidence: 99%

Prognostic, predictive, and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer

et al. 2018

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We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in colorectal cancer (CRC) according to disease stage and chemotherapy sensitivity in preclinical models. CDX2 expression was evaluated in 1045 stage I–IV primary CRCs by gene expression (n = 403) or immunohistochemistry (n = 642) and in relation to 5‐year relapse‐free survival (RFS), overall survival (OS), and chemotherapy. Pharmacogenomic associations between CDX2 expression and 69 chemotherapeutics were assessed by drug screening of 35 CRC cell lines. CDX2 expression was lost in 11.6% of cases and showed independent poor prognostic value in multivariable models. For individual stages, CDX2 was prognostic only in stage IV, independent of chemotherapy. Among stage I–III patients not treated in an adjuvant setting, CDX2 loss was associated with a particularly poor survival in the BRAF‐mutated subgroup, but prognostic value was independent of microsatellite instability status and the consensus molecular subtypes. In stage III, the 5‐year RFS rate was higher among patients with loss of CDX2 who received adjuvant chemotherapy than among patients who did not. The CDX2‐negative cell lines were significantly more sensitive to chemotherapeutics than CDX2‐positive cells, and the multidrug resistance genes MDR1 and CFTR were significantly downregulated both in CDX2‐negative cells and in patient tumors. Loss of CDX2 in CRC is an adverse prognostic biomarker only in stage IV disease and appears to be associated with benefit from adjuvant chemotherapy in stage III. Early‐stage patients not qualifying for chemotherapy might be reconsidered for such treatment if their tumor has loss of CDX2 and mutated BRAF.

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Section: Discussionmentioning

confidence: 99%

Prognostic, predictive, and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer

et al. 2018

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“…Our study cases come from a described series of CRCs, 7 including specimens up to the age of 15 years, that are useful for testing sample requirements, given the fact that, in clinical practice, mutation detection experiments are usually performed on archival material. DNA from paraffin-embedded samples is seriously degraded after formalin treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The study cases come from a previously described series of serrated and conventional CRCs from January 1995 to December 2009December (mean, 2003; SD, Ϯ3.0 years). 7 All patient identifiers were deleted to protect patient confidentiality, and the study was approved by the local ethical board.…”

Section: Study Cases and Dna Extractionmentioning

confidence: 99%

Comparison of Allelic Discrimination by dHPLC, HRM, and TaqMan in the Detection of BRAF Mutation V600E

Carbonell

Turpin

Torres-Moreno

et al. 2011

The Journal of Molecular Diagnostics

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The V600E mutation in the BRAF oncogene is associated with colorectal carcinomas, with mismatch-repair deficiency and, recently, with nonresponse to epidermal growth factor receptor inhibitor therapy. The use of reliable techniques for its detection is important. The aim of our study was to compare the performance characteristics in V600E detection of denaturing high-performance liquid chromatography (dHPLC) and high-resolution melting (HRM) with TaqMan allelic discrimination as well as direct-sequencing methods in a series of 195 colorectal paraffinembedded specimens up to the age of 15 years. The effectiveness for obtaining results on mutation status was best using TaqMan (96.9%), followed by dHPLC (93.3%), HRM (88.7%), and sequencing (88.2%). In general, TaqMan was best for analyzing older tissues, whereas sequencing was the least efficient. Heterozygotic V600E was detected in 11.6%, 9.9%, 11.6%, and 9.9% of tissues using TaqMan, dHPLC, HRM, and sequencing, respectively. Result concordances between dHPLC and TaqMan or sequencing were excellent ( ‫؍‬ 0.9411 and ‫؍‬ 0.8988, respectively); for HRM, the concordances were good ( ‫؍‬ 0.7973 and ‫؍‬ 0.7488, respectively). By using DNA dilutions from tumor tissue, a minimum of 10% of V600E harboring cancer content was required for the analysis by dHPLC and HRM. dHPLC could detect four non-V600E mutations, whereas HRM detected one. Our results indicate that dHPLC and HRM are techniques that can be reliably used for the detection of the BRAFV600E mutation in Recent advances in DNA sequencing technology have made it possible to use high-throughput sequencing on the entire human colorectal cancer (CRC) spectrum, finding 848 genes that may be somatically mutated. 1,2 The subsequent study of these mutations in CRC specimens worldwide would be facilitated by the use of less expensive and more efficient screening methods for mutation detection. Because most of these mutations are found in heterozygosis, screening techniques based on heteroduplex detection, such as denaturing high-performance liquid chromatography (dHPLC) or high-resolution melting (HRM) analysis, are strongly recommended. The V600E mutation in the BRAF oncogene has been found in CRCs with mismatch-repair gene deficiency. Familial CRCs with mismatch-repair gene deficiency do not harbor this mutation; rather, V600E is associated with the sporadic form of CRC associated with mismatch-repair gene deficiency. In addition to the diagnostic value of the BRAF mutation assessment, recent evidence 3,4 has demonstrated that stage IV CRCs with the BRAF V600E mutation do not respond to epidermal growth factor receptor inhibitor therapy, thus extending its value to predictive grounds. In previous articles, 5 V600E detection using TaqMan chemistry (Applied Biosystem, Foster City, CA) saved cost, time, and manual labor over direct sequencing, with the former showing 100% sensitivity and 100% specificity when the latter is considered as the reference method. Also, HRM has proved to be a reliable technique for V600E detection...

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“…Serrated polyps form a heterogeneous group of colorectal lesions that include hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and a combination of two or more characteristics, formerly classified as mixed polyps (MP) (9). HPs are the most common serrated polyp and they have been increasingly suggested to be precursor lesions, since they may develop into other serrated polyps as SSA, TSA or MP to CRC (10).…”

Section: Introductionmentioning

confidence: 99%

KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy

et al. 2014

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Abstract. Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Adenoma is the main precursor lesion and, recently, the serrated polyps were described as a group of colorectal lesions with malignant potential. The morphologic and biologic characterizations of serrated polyps remain limited. The aim of the present study was to determine the frequency of KRAS and BRAF mutations and microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. A series of 342 precursor lesions were removed from 155 patients during colonoscopy. After morphologic classification, molecular analysis was performed in 103 precursor lesions, and their genetic profile compared with 47 sporadic CRCs. Adenomas were the main precursor lesions (70.2%). Among the serrated polyps, the main precursor lesion was hyperplastic polyps (HPs) (82.4%), followed by sessile serrated adenomas (12.7%) and traditional serrated adenomas (2.0%). KRAS mutations were detected in 13.6% of the precursor lesions, namely in adenomas and in HPs, but in no serrated adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions, mainly associated with serrated polyps and absent in adenomas (P<0.001). High MSI (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role of KRAS and BRAF mutations in CRC carcinogenesis, a crucial step in implementing CRC screening strategies.

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Clinicopathologic study of 85 colorectal serrated adenocarcinomas: further insights into the full recognition of a new subset of colorectal carcinoma

Cited by 91 publications

References 17 publications

Prognostic, predictive, and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer

Prognostic, predictive, and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer

Comparison of Allelic Discrimination by dHPLC, HRM, and TaqMan in the Detection of BRAF Mutation V600E

KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy

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