Molecular Subtypes Are Frequently Discordant Between Lesions in Patients With Synchronous Colorectal Cancer: Molecular Analysis of 59 Patients

Arakawa, K; Hata, Keisuke; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Toshiaki; Nishikawa, Takeshi; Sasaki, Kazuhito; Shuno, Yasutaka; Kaneko, Manabu; Hiyoshi, Masaya; Emoto, Shigenobu; Murono, Koji; Sonoda, Hirofumi; Okada, Satoshi; Ishihara, Soichiro

doi:10.21873/anticanres.13258

Cited by 3 publications

(9 citation statements)

References 33 publications

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“…Evaluating the MSS status was necessary for predictive purposes. It is known that over 10% of CRCs might present microsatellite instability (MSI) and do not benefit from 5-FU-based chemotherapy [12,13,16]. In this study, all of the cases were MSS tumors.…”

Section: Discussionmentioning

confidence: 72%

“…Examination of KRAS and BRAF mutation statuses is indicated in metastatic cases since wildtype KRAS and BRAF carcinomas are eligible for anti-EGFR therapy [13]. There are no guidelines regarding the discordant cases and their postoperative oncologic management [17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that the presence of a mucinous component and BRAF mutation rate appear at a higher frequency in SCRCs than in solitary CRCs, but none of our cases had BRAF mutations. [13,19,20]. In the literature, the reported concordance rates for MSI, KRAS mutation, and BRAF mutation between tumors in the same patient varied from 9-30%, 11-40% and 14%, respectively [9,13,21].…”

Section: Discussionmentioning

confidence: 99%

“…In the literature, the reported concordance rates for MSI, KRAS mutation, and BRAF mutation between tumors in the same patient varied from 9-30%, 11-40% and 14%, respectively [9,13,21]. In a study on 59 patients with SCRCs, Arakawa et al found that, although low, there was significant correlation between the subtypes of MSI, BRAF mutation, and β-catenin between the lesions in each patient, while KRAS mutation had poor correlation [13]. Although one of our patients presented with a familial history of CRC the connection between genetic background and the incidence of SCRCs is not confirmed [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Surgical treatment is the primary therapeutic approach, followed by chemotherapy, which is mainly based on 5-Fluorouracil (5-FU) derivates [7,11,12]. In metastatic cases, targeted therapy focusing on the SCRCs with distinct molecular profiles requires molecular profile examination, knowing that BRAF and KRAS mutant tumors show resistance to anti-EGFR (epidermal growth factor receptor) therapy [13]. However, this has not yet become a therapeutic guideline.…”

Section: Introductionmentioning

confidence: 99%

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Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

et al. 2021

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Background: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. Methods: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers β-catenin and E-cadherin, same as KRAS and BRAF mutations. Results: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. Conclusions: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

et al. 2021

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The CpG Island Methylator Phenotype Status in Synchronous and Solitary Primary Colorectal Cancers: Prognosis and Effective Therapeutic Drug Prediction

Weng,

Huang

2024

IJMS

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Synchronous colorectal cancer (sCRC) is characterized by the occurrence of more than one tumor within six months of detecting the first tumor. Evidence suggests that sCRC might be more common in the serrated neoplasia pathway, marked by the CpG island methylator phenotype (CIMP), than in the chromosomal instability pathway (CIN). An increasing number of studies propose that CIMP could serve as a potential epigenetic predictor or prognostic biomarker of sCRC. Therapeutic drugs already used for treating CIMP-positive colorectal cancers (CRCs) are reviewed and drug selections for sCRC patients are discussed.

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Inoperable de novo metastatic colorectal cancer with primary tumour in situ: Evaluating discordant responses to upfront systemic therapy of the primary tumours and metastatic sites and complications arising from primary tumours (experiences from an Irish Cancer Centre)

et al. 2021

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Systemic therapy is the mainstay of treatment for de novo metastatic colorectal cancer (mCRC). Heterogeneity between primary tumours and metastases may lead to discordant responses to systemic therapy at these sites. The aim of the present study was to examine these discrepancies and to evaluate the rates of complications arising from the primary tumour and the strategies employed to manage these complications. Electronic medical records were screened for patients eligible for data analysis between January 1st, 2014 and December 31st, 2019. All patients diagnosed with de novo mCRC with primary tumour in situ at the time of initial systemic therapy were included in data analysis. Responses in primary tumour and metastatic sites (according to the Response Evaluation Criteria In Solid Tumours v1.1), discrepancies in these responses and rates of complications arising from primary tumours were assessed along with patient, pathological or molecular factors that may be associated with these discrepant responses or primary tumour complications. A total of 50 patients were identified (median age, 62 years). Right-colon, left-colon and rectal primary tumours comprised 34, 44 and 22% of CRC cases, respectively. All patients received 5-fluorouracil-based chemotherapy (either alone or in combination with oxaliplatin or irinotecan). Disease response (DR), stable disease (SD) and progressive disease (PD) were observed as the first response to systemic therapy in 24, 62 and 12% of primary tumours and in 36, 18 and 44% of metastatic sites, respectively. Only 36% of patients demonstrated concordant responses between the primary tumours and metastases, while the remaining 62% demonstrated discordant responses between the primary tumour and distant metastases (22% had DR with SD; 36% had DR or SD with PD; and 4% had PD with SD in the primary tumour and metastases, respectively). Restaging images were not available for 2% of the patients. Approximately 30% of patients developed complications from primary tumours, including bowel obstruction (6.12%), perforation (6%), rectal pain (6%) and rectal bleeding (10%). Approximately 10% of patients underwent palliative stoma creation. Additionally, 12% required palliative radiotherapy to the primary tumour (due to localized complications arising from the tumour). Discordant responses to systemic therapy between primary tumours and metastases occurred in 60% of patients with de novo mCRC (with primary tumour in situ at the time of first systemic therapy). The observations of the present study have potential implications for molecular tissue analysis to help guide systemic therapy. Tissue from metastatic sites may be preferable to confirm biomarker status in mCRC based on this study.

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Molecular Subtypes Are Frequently Discordant Between Lesions in Patients With Synchronous Colorectal Cancer: Molecular Analysis of 59 Patients

Cited by 3 publications

References 33 publications

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

The CpG Island Methylator Phenotype Status in Synchronous and Solitary Primary Colorectal Cancers: Prognosis and Effective Therapeutic Drug Prediction

Inoperable de novo metastatic colorectal cancer with primary tumour in situ: Evaluating discordant responses to upfront systemic therapy of the primary tumours and metastatic sites and complications arising from primary tumours (experiences from an Irish Cancer Centre)

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