Clinicopathological and molecular differences between right-sided and left-sided colorectal cancer in Japanese patients

Natsume, Soichiro; Yamaguchi, Tatsuro; Takao, Misato; Iijima, Takeru; Wakaume, Rika; Takahashi, Keiichi; Matsumoto, Hiroshi; Nakano, Daisuke; Horiguchi, Shinichiro; Koizumi, Koichi; Miyaki, Michiko

doi:10.1093/jjco/hyy069

Cited by 35 publications

(28 citation statements)

References 44 publications

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“…In this study, for the eastern China patients, the frequency of RCC was 18.25%, lower than in previous reports from other regions in China such as Shanghai (24.4% and 25.3%), Shantou (36.9%), Tianjin (50.6%), and Guangdong (17.5%), as well as Japan (26.3% and 29.3%) (Xu et al, 2010;Watanabe et al, 2012;Liu et al, 2017;Peng et al, 2017;Qin et al, 2017;Natsume et al, 2018;Guo et al, 2019), whereas the RCC frequency in the United States was as high as 42% (Siegel et al, 2014). This finding indicates that the distribution of RCC in eastern China patients might be different compared to those of other regions in China and Western countries.…”

Section: Discussioncontrasting

confidence: 78%

“…For the molecular markers in CRC, the mutation rates of MSI-H, KRAS, and NRAS were reported to be 6-15% (Horvat and Stabuc, 2011;Gelsomino et al, 2016;Chang et al, 2017; Samstein and Chan, 2017), 38.5-40% (Natsume et al, 2018), and 1-6% respectively (Downward, 2003). In our study, the frequencies of the MSI-H (6.31%), KRAS (40.15%), and NRAS (3.85%) mutation were in accordance with those in the Western countries and other regions in China, whereas the BRAF (2.29%) mutation was specifically lower.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, the frequencies of the MSI-H (6.31%), KRAS (40.15%), and NRAS (3.85%) mutation were in accordance with those in the Western countries and other regions in China, whereas the BRAF (2.29%) mutation was specifically lower. The BRAF mutation rate was reported to be around 2.5%-6.15% in different regions of China (Peng et al, 2017;Wang et al, 2018), and 3.7-11.3% in other Asian countries (Lee et al, 2015;Fujiyoshi et al, 2017;Natsume et al, 2018), for the eastern China patients, this incidence was 2.23%, much lower than those of Western countries, reported as 17-19.4% (Hutchins et al, 2011;Loupakis et al, 2015). We analyzed the pTNM stage and found that the BRAF mutation was mostly detected at stage III which was in line with previous data (Sayagues et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Effect of Tumor Location on Clinicopathological and Molecular Markers in Colorectal Cancer in Eastern China Patients: An Analysis of 2,356 Cases

et al. 2020

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Colorectal cancer (CRC) has become a major health concern in China due to its increasing incidence and mortality. This study aimed to clarify the relationship between tumor locations and the clinicopathological molecular marker features in eastern China CRC patients. We continuously collected data on 2,356 CRC patients who underwent surgical resection from January 2017 to April 2019. Right-sided colorectal cancer (RCC), was located from the cecum to the transverse colon and left-side colorectal cancer (LCRC) was located from the splenic flexure to the rectum. The clinicopathological indices (including age, sex, pTNM stage, mucinous production, and distant metastasis) and frequency of molecular markers such as KRAS, NRAS, BRAF, and microsatellite instability (MSI) were statistically analyzed between the RCC and LCRC groups. The associations between clinicopathological characters and molecular markers were also investigated. LCRC and RCC proportions in eastern China CRC patients were 81.75% and 18.25%, respectively. RCC (vs. LCRC) was more frequently observed with higher frequencies of MSI-high (MSI-H) and BRAF mutations in female and younger patients, and was closely associated with metastasis, poor differentiation, and mucinous tumors. Tumor location also showed significant differences in bowel wall infiltration degree and pTNM stage. Mutation rates of KRAS, NRAS, MSI, and BRAF were 40.15%, 3.85%, 6.31%, and 2.30%, respectively. Patients with a KRAS mutation tended to be female, had mucinous, perineural invasive, and polypoid tumor. Those with NRAS mutation tended to develop well-differentiated ulcerative tumors. The BRAF mutation was more relevant with lymph node involvement, deeper infiltration of the bowel wall, mucinous, poorly-differentiated tumor with thrombus, and perineural invasion. Furthermore, MSI-H was more commonly found in younger patients with deeper bowel wall infiltration and a poorly-differentiated polypoid tumor, whereas MSS patients tended to develop lymph node involvement, and a mucinous and perineural invasive tumor. In our study, we found that LCRC and RCC showed different features on the clinicopathological and molecular markers in eastern China CRC patients. Since our data differ from those of Western countries and other

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effect of Tumor Location on Clinicopathological and Molecular Markers in Colorectal Cancer in Eastern China Patients: An Analysis of 2,356 Cases

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“…We also tried to develop a signature to predict CIMP status for stage II and III LCC. However, the prevalence rate of CIMP+ among LCC was only 2.04-6.67% in the training and validation datasets ( Supplementary Table 3), and the statistics showed that the prevalence rate is about 2.67% in several studies (Natsume et al, 2018). There were so few LCC CIMP+ samples that we could not train or validate a signature to predict the CIMP status for LCC samples.…”

Section: Discussionmentioning

confidence: 94%

A Qualitative Transcriptional Signature for Predicting CpG Island Methylator Phenotype Status of the Right-Sided Colon Cancer

et al. 2020

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“…In our study, the KRAS mutation rate was 27.6%, and this rate was similar to that in conventional CRCs. 27 The most frequently mutated gene among NGS cases was TP53. Among the 42 cases of CRCs with enteroblastic marker expression, the TP53 mutation rate was 52.4% (22 of 42) and the p53 overexpression rate was 64.3% (27 of 42).…”

Section: Discussionmentioning

confidence: 99%

Molecular and clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation

et al. 2020

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Background Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colorectal malignancy with expression of enteroblastic markers (glypican 3, SALL4, AFP); however, the clinicopathological and epidemiological features are not fully elucidated. Aims The aims of this study were to elucidate and establish the molecular and clinicopathological characteristics of CAED. Materials and Methods In addition to three cases recently diagnosed as CAED, colorectal carcinoma (CRC) with expression of enteroblastic markers were selected by using immunohistochemistry (IHC) on tissue microarrays of 988 advanced CRC. We employed next‐generation sequencing (NGS) and Sanger sequencing for the detection of genetic alterations. IHC for p53 and HER2, HER2‐FISH and MSI status was also investigated. Survival analyses for clinicopathological parameters were performed using Kaplan–Meier methods. Results Thirty‐nine cases (4.0%) were positive for at least one enteroblastic marker. Histological evaluation of the total of 42 cases revealed that 10 contained tumour cells with clear cytoplasm. Enteroblastic marker‐positive cases had aggressive behaviour and poor prognosis. NGS revealed TP53 as the most frequently mutated gene. The rate of HER2‐positive cases and MSI‐H cases was 9.5% (four of 42) and 12.2% (five of 41), respectively. Among these 42 cases, there were no molecular and clinicopathological differences according to the presence of tumour cells with clear cytoplasm. Conclusions Enteroblastic marker‐positive CRC could be grouped together as CAED regardless of clear cell cytoplasm. Using this definition, the frequency of CAED is 4.0% and has a poorer prognosis than that for conventional CRCs. HER2 targeted therapy would be a meaningful treatment for CAED, and CAEDs contain both MSI‐H and MSI‐stable CRCs, although the MSS phenotype is dominant.

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Clinicopathological and molecular differences between right-sided and left-sided colorectal cancer in Japanese patients

Cited by 35 publications

References 44 publications

Effect of Tumor Location on Clinicopathological and Molecular Markers in Colorectal Cancer in Eastern China Patients: An Analysis of 2,356 Cases

Effect of Tumor Location on Clinicopathological and Molecular Markers in Colorectal Cancer in Eastern China Patients: An Analysis of 2,356 Cases

A Qualitative Transcriptional Signature for Predicting CpG Island Methylator Phenotype Status of the Right-Sided Colon Cancer

Molecular and clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation

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