Distinctive clinicopathological features ofKi-ras mutated colorectal cancers

Lin, Jen Kou; Chang, Shih Ching; Wang, Huann Sheng; Yang, Shung Haur; Jiang, Jeng Kai; Chen, Wei Chone; Lin, Tzu Chen; Li, Anna Fen Yau

doi:10.1002/jso.20438

Cited by 15 publications

(15 citation statements)

References 35 publications

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“…10,11,16,17 Like BRAF-mutated carcinomas, KRAS-mutated carcinomas showed an increased frequency of mucinous differentiation. This finding has been previously observed by Lin et al 28 and more recently by Pai et al, 8 who reported that 32% of proximal KRAS-mutated carcinoma showed mucinous differentiation compared with 25% of null carcinomas. Maltzman et al 29 previously reported that patients with KRAS mutated adenomas were significantly older than adenoma patients without a KRAS mutation.…”

Section: Discussionsupporting

confidence: 87%

Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features

et al. 2013

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KRAS-mutated carcinomas comprise 35-40% of all colorectal carcinomas but little is known about their characteristics. The aim of this study was to examine the pathological and molecular features of KRAS-mutated colorectal carcinomas and to compare them with other carcinoma subgroups. KRAS mutation testing was performed in 776 incident tumors from the Melbourne Collaborative Cohort Study. O 6 -methylguanine DNA methyltransferase (MGMT) status was assessed using both immunohistochemistry and MethyLight techniques. Microsatellite instability (MSI) phenotype and BRAF V600E mutation status were derived from earlier studies. Mutation in KRAS codon 12 or codon 13 was present in 28% of colorectal carcinomas. Compared with KRAS wildtype carcinomas, KRAS-mutated carcinomas were more frequently observed in contiguity with a residual polyp (38 vs 21%; Po0.001), demonstrated mucinous differentiation (46 vs 31%; P ¼ 0.001) and were associated with different MSI status (Po0.001) and with MGMT methylation (47 vs 21%; P ¼ 0.001). Compared with tumors demonstrating neither BRAF nor KRAS mutation, KRAS-mutated carcinomas showed more frequent location in the proximal colon (41 vs 27%; P ¼ 0.001), mucinous differentiation (46 vs 25%; Po0.001), presence of a contiguous polyp (38 vs 22%; Po0.001), MGMT methylation (47 vs 26%; P ¼ 0.01) and loss of MGMT immunohistochemical expression (27 vs 19%; P ¼ 0.02). KRAS-mutated carcinomas were distributed in a bimodal pattern along the proximal-distal axis of the colorectum. Compared with male subjects, female subjects were more likely to have KRAS-mutated carcinoma in the transverse colon and descending colon (39 vs 15%; P ¼ 0.02). No difference in overall survival was observed in patients according to their tumor KRAS mutation status. In summary, KRAS-mutated carcinomas frequently develop in contiguity with a residual polyp and show molecular features distinct from other colorectal carcinomas, in particular from tumors with neither BRAF nor KRAS mutation.

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Section: Discussionsupporting

confidence: 87%

Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features

et al. 2013

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“…Like CRCs with BRAF mutations, KRAS -mutated carcinomas had an increased frequency of the mucinous feature. Several others have also reported this finding [27, 30]. …”

Section: Discussionsupporting

confidence: 69%

The prognostic significance of KRAS and BRAF mutation status in Korean colorectal cancer patients

Won

Lee

et al. 2017

BMC Cancer

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Background BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients.MethodsFrom July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary’s Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status. All data were reviewed retrospectively.ResultsAmong 1096 patients, 401 (36.7%) had KRAS mutations and 44 (4.0%) had BRAF mutations. Of 83 patients, 77 (92.8%) had microsatellite stable (MSS) or MSI low (MSI-L) status while 6 (7.2%) patients had MSI high (MSI-H) status. Patients with BRAF mutation demonstrated a worse disease-free survival (DFS, HR 1.990, CI 1.080–3.660, P = 0.02) and overall survival (OS, HR 3.470, CI 1.900–6.330, P < 0.0001). Regarding KRAS status, no significant difference was noted in DFS (P = 0.0548) or OS (P = 0.107). Comparing the MSS/MSI-L and MSI-H groups there were no significant differences in either DFS (P = 0.294) or OS (P = 0.557).Conclusions BRAF mutation, rather than KRAS, was a significant prognostic factor in Korean CRC patients at both early and advanced stages. The subgroup analysis for MSI did not show significant differences in clinical outcome. BRAF should be included in future larger prospective biomarker studies on CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3381-7) contains supplementary material, which is available to authorized users.

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“…The right and left colon tumors are distinct tumoral structures due to their epidemiological, clinicopathological and molecular biological features. Right colon cancer is associated with female gender, advanced age, advanced stage and poorly differentiated mucinous histological type (Lin et al, 2006;Benedix et al, 2010;Pai et al, 2012;Rosty et al, 2013). However, no relationship was established with mucinous histology in our study.…”

Section: Discussioncontrasting

confidence: 63%

Distribution of KRAS and BRAF Mutations in Metastatic Colorectal Cancers in Turkish Patients

Görükmez

Yakut²,

Görükmez

et al. 2016

Asian Pacific Journal of Cancer Prevention

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The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the patients with mCRC had KRAS mutations and the only clinicopathological factor related to this mutation was tumor location. Future studies with larger patient groups should yield more accurate data regarding the molecular mechanism of CRC and the association between KRAS and BRAF mutations and clinicopathological features.

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Distinctive clinicopathological features ofKi-ras mutated colorectal cancers

Abstract: Ki-ras mutated colorectal tumors have a higher mucin production and higher differentiation, and are associated with lower plasma folate levels and a relatively poorer disease outcome.

Cited by 15 publications

References 35 publications

Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features

Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features

The prognostic significance of KRAS and BRAF mutation status in Korean colorectal cancer patients

Distribution of KRAS and BRAF Mutations in Metastatic Colorectal Cancers in Turkish Patients

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