The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer

Warusavitarne, Janindra; Schnitzler, Margaret

doi:10.1007/s00384-006-0228-0

Cited by 47 publications

(50 citation statements)

References 81 publications

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“…Current treatment of small bowel adenocarcinoma commonly includes surgical resection and adjuvant 5-fluorouracil as it is standard in colorectal cancer (1). It has been reported that microsatellite instability-positive colorectal cancer does not response to treatment with 5-fluorouracil as well as microsatellite stable colorectal cancer (48). Because our study and others showed that the frequency of microsatellite instability in celiac disease-related small bowel adenocarcinomas is much higher (43-73%; refs.…”

Section: Discussionmentioning

confidence: 56%

High-Resolution Array Comparative Genomic Hybridization in Sporadic and Celiac Disease–Related Small Bowel Adenocarcinomas

Diosdado

Buffart

Watkins

et al. 2010

Clinical Cancer Research

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Purpose: The molecular pathogenesis of small intestinal adenocarcinomas is not well understood. Understanding the molecular characteristics of small bowel adenocarcinoma may lead to more effective patient treatment.Experimental Design: Forty-eight small bowel adenocarcinomas (33 non-celiac disease related and 15 celiac disease related) were characterized for chromosomal aberrations by high-resolution array comparative hybridization, microsatellite instability, and APC promoter methylation and mutation status. Findings were compared with clinicopathologic and survival data. Furthermore, molecular alterations were compared between celiac disease-related and non-celiac disease-related small bowel adenocarcinomas.Results: DNA copy number changes were observed in 77% small bowel adenocarcinomas. The most frequent DNA copy number changes found were gains on 5p15. 33-5p12, 7p22.3-7q11.21, 7q21.2-7q21.3, 7q22.1-7q34, 7q36.1, 7q36.3, 8q11.21-8q24.3, 9q34.11-9q34.3, 13q11-13q34, 16p13.3, 16p11.2, 19q13.2, and 20p13-20q13.33, and losses on 4p13-4q35.2, 5q15-5q21.1, and 21p11.2-21q22.11. Seven highly amplified regions were identified on 6p21.1, 7q21.1, 8p23.1, 11p13, 16p11.2, 17q12-q21.1, and 19q13.2. Celiac disease-related and non-celiac disease-related small bowel adenocarcinomas displayed similar chromosomal aberrations. Promoter hypermethylation of the APC gene was found in 48% non-celiac disease-related and 73% celiac disease-related small bowel adenocarcinomas. No nonsense mutations were found. Thirty-three percent of non-celiac disease-related small bowel adenocarcinomas showed microsatellite instability, whereas 67% of celiac disease-related small bowel adenocarcinomas were microsatellite unstable.Conclusions: Our study characterized chromosomal aberrations and amplifications involved in small bowel adenocarcinoma. At the chromosomal level, celiac disease-related and non-celiac disease-related small bowel adenocarcinomas did not differ. A defect in the mismatch repair pathways seems to be more common in celiac disease-related than in non-celiac disease-related small bowel adenocarcinomas. In contrast to colon and gastric cancers, no APC nonsense mutations were found in small bowel adenocarcinoma. However, APC promoter methylation seems to be a common event in celiac disease-related small bowel adenocarcinoma. Clin Cancer Res; 16(5); 1391-401. ©2010 AACR.

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Section: Discussionmentioning

confidence: 56%

High-Resolution Array Comparative Genomic Hybridization in Sporadic and Celiac Disease–Related Small Bowel Adenocarcinomas

Diosdado

Buffart

Watkins

et al. 2010

Clinical Cancer Research

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“…It is recognised that defective DNA mismatch repair (MMR) leads to MSI and results in resistance to many antineoplastic drugs, such as antimetabolites, alkylating, and platinum agents, and inhibitors of topoisomerases. There are some evidences in vitro that suggest a correlation between response to 5-FU, OXA, and IRI and MSI (Magrini et al, 2002;Arnold et al, 2003;Warusavitarne and Schnitzler, 2007). Our analysis plan did not include an MSI analysis.…”

Section: Discussionmentioning

confidence: 99%

Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy

et al. 2009

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The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5 -29.2%) and 49% (95% CI, 42.2 -55.8%), respectively (P ¼ 0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the nonmucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27 -3.31; P ¼ 0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05 -2.40; P ¼ 0.0267), together with performance status ECOG 2, number of metastatic sites X2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.

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“…Clinical studies investigating the effect of 5-fluorouracil and survival in MMR-deficient colorectal cancer have mainly been retrospective and derived from unselected nonrandomized groups and therefore potentially biased (21). However, Ribic et al who analyzed 570 tissue specimens of stage II and III colorectal cancer from pooled randomized controlled trials described no advantage to 5-fluorouracil treatment in patients with MSI-H colorectal cancers (22).…”

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confidence: 99%

RHAMM, p21 Combined Phenotype Identifies Microsatellite Instability-High Colorectal Cancers with a Highly Adverse Prognosis

Zlobec

Baker

Terracciano

et al. 2008

Clinical Cancer Research

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Purpose: The aim of this study was to identify prognostic subgroups of microsatellite instabilityhigh (MSI-H) colorectal cancers by combined analysis of 10 well-established immunohistochemical tumor markers and 7 clinicopathologic features. Experimental Design: Using a tissue microarray, immunohistochemistry was done on 223 cases of MSI-H cancers for the following protein markers: raf-1kinase inhibitor protein, receptor for hyaluronic acid^mediated motility, apoptosis protease activating factor-1, mammalian sterile20-like kinase 1, p21, p27, p53, ephrin B2 receptor, Ki-67, and epidermal growth factor receptor. Seven clinicopathologic features and all tumor markers were evaluated in univariate and multivariable analyses. Conclusion: These results suggest that the combined phenotype of RHAMM and p21 expression is an invaluable independent prognostic immunohistochemical profile in MSI-H colorectal cancer. Based on the prognostic subgroups identified in our cohort, node-negative patients overexpressing RHAMM but with loss of p21 may derive a potential benefit from postoperative treatment, whereas adjuvant chemotherapy should be reconsidered for MSI-H node-positive RHAMM-tumors.

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The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer

Abstract: Available evidence suggests that MSI-H CRC have different behaviour patterns and response to chemotherapy compared with MSS CRC.

Cited by 47 publications

References 81 publications

High-Resolution Array Comparative Genomic Hybridization in Sporadic and Celiac Disease–Related Small Bowel Adenocarcinomas

High-Resolution Array Comparative Genomic Hybridization in Sporadic and Celiac Disease–Related Small Bowel Adenocarcinomas

Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy

RHAMM, p21 Combined Phenotype Identifies Microsatellite Instability-High Colorectal Cancers with a Highly Adverse Prognosis

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