Primary Mucinous Adenocarcinomas and Signet-Ring Cell Carcinomas of Colon and Rectum

Secco, G B; Fardelli, R; Campora, E; Lapertosa, G; Gentile, R; Zoli, S; C, Prior

doi:10.1159/000227306

Cited by 140 publications

(100 citation statements)

References 6 publications

(21 reference statements)

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“…The reported 5-year survival in the literature is 9-37%, [1][2][3][4][5][6][7][8][9][10] which is comparable to the 33% survival in this study. The literature contains limited data on the molecular features of signet ring cell carcinoma.…”

Section: Discussionsupporting

confidence: 84%

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Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma

et al. 2012

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The relationship of molecular abnormalities with clinicopathologic features and survival in colorectal signet ring cell carcinoma, and its comparison with mucinous and conventional adenocarcinomas, has not been well studied. High-level microsatellite instability, loss of heterozygosity (LOH) at four loci, CpG island methylation phenotype based on seven loci, BRAF V600E mutation and KRAS mutation in signet ring cell carcinoma were compared with mucinous and conventional adenocarcinomas. The relationship of these molecular features in signet ring cell carcinoma with clinicopathologic features and survival was examined. LOH was observed in 93% of signet ring cell carcinomas compared with 62 and 70% of mucinous and conventional adenocarcinomas. Also, 80% of signet ring cell carcinomas with high-level microsatellite instability showed LOH compared with 14% each of mucinous and conventional adenocarcinomas. High-level microsatellite instability, CpG island methylation phenotype-positive status and BRAF V600E mutation were more often seen in signet ring cell carcinoma and mucinous adenocarcinoma compared with conventional adenocarcinoma. BRAF V600E mutation was significantly associated with CpG island methylation phenotype-positive status. Stage and BRAF V600E mutation in microsatellite-stable cases were the only variables with an affect on survival. In conclusion, chromosomal instability manifested by LOH is nearly a universal finding in signet ring cell carcinoma, including cases with highlevel microsatellite instability. This may explain the aggressive behavior of signet ring cell carcinoma irrespective of high-level microsatellite-instability status. BRAF V600E mutation and CpG island methylation phenotypepositive status are similar in signet ring cell carcinoma and mucinous adenocarcinoma but more frequent when compared with conventional adenocarcinoma. In signet ring cell carcinoma, BRAF V600E mutation adversely affects survival in microsatellite-stable tumors, but not in high-level microsatellite-unstable tumors. The high frequency of methylation and BRAF V600E mutation suggests that many signet ring cell carcinomas may be related to the serrated pathway of carcinogenesis.

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Section: Discussionsupporting

confidence: 84%

“…[1][2][3][4][5][6][7][8][9][10] By definition, 450% of tumor cells have signet ring cell morphology. 11 Signet ring histology is considered an independent adverse prognostic factor by the American Joint Committee on Cancer and the College of American Pathologists.…”

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confidence: 99%

Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma

et al. 2012

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“…The prognostic significance of mucinous carcinoma is controversial. In some studies, mucinous histology has been shown to be an independent negative prognostic factor (Connelly et al, 1991;Green et al, 1993;Secco et al, 1994), but not in others (Minsky et al, 1987;Green et al, 1993;Enriquez et al, 1998;Consorti et al, 2000). Both the American Joint Committee on Cancer and the College of American Pathologists consider that the mucinous subtype has not been proven as a statistically significant prognostic factor independent of histological grade (Compton et al, 2000a(Compton et al, , 2000b.…”

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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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“…[9][10][11][12][13][14][15][16] Mucinous carcinoma is a histologic subtype constituting 11-15% of colorectal cancer. [17][18][19][20][21] Mucinous histology has been shown to be an independent adverse prognostic factor in some studies, 19,[21][22][23] but not in others. 17,18,20,24,25 The current consensus of the College of American Pathologists (CAP) and American Joint Committee on Cancer is that mucinous differentiation is not proven as a statistically significant prognostic factor independent of histologic grade.…”

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confidence: 99%

Mucinous carcinoma of the colon: correlation of loss of mismatch repair enzymes with clinicopathologic features and survival

et al. 2004

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Colorectal carcinoma with microsatellite instability (MSI-H) has a characteristic clinicopathologic profile, typically forming right-sided, lymphocyte-rich tumors that are often mucinous. Mucinous histology in general has been linked to adverse prognosis in some studies, but not in others. MSI-H carcinoma, in contrast, has a better prognosis than microsatellite stable carcinoma in most studies. We assessed the relationship between MSI status, clinicopathologic features and outcome for 248 consecutive patients with resected mucinous carcinoma. All cases were reviewed to confirm mucinous histology. Immunohistochemical stains for DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 were performed on a representative block from each case. Tumors lacking expression of a mismatch repair enzyme were designated MSI-H; all others were classified as microsatellite stable. Age, sex, tumor size, site, grade, stage, growth pattern, Crohn's-like reaction, vascular invasion and number of tumor-infiltrating lymphocytes were evaluated without knowledge of MSI status or patient outcome. 72 (29.3%) mucinous carcinomas were MSI-H. Compared to microsatellite stable mucinous cancers, they were more likely to be right-sided (83.3 vs 48.6%, Po0.001), have a Crohn's -like reaction (65.7 vs 29.8%, Po0.001) and have many tumor infiltrating lymphocytes (72.2 vs 20.8%, Po0.001). MSI-H mucinous cancers presented more often as localized disease (66.7 vs 38.1%, Po0.001) and less often with lymph node (26.4 vs 44.9%) or distant (4.2 vs 16.5%) metastases. In univariate analysis, MSI had a favorable effect on ageadjusted survival (hazard ratio 0.597, P ¼ 0.02). In multivariate analysis, age, grade, Crohn's-like reaction and stage were independent predictors of survival, but MSI status was not. In conclusion, MSI-H mucinous carcinomas are right-sided, low-stage tumors with Crohn's-like reaction and tumor-infiltrating lymphocytes. The outcome for MSI-H mucinous carcinoma is better than that of microsatellite-stable mucinous carcinoma, but MSI status is not an independent predictor of survival.

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Primary Mucinous Adenocarcinomas and Signet-Ring Cell Carcinomas of Colon and Rectum

Cited by 140 publications

References 6 publications

Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma

Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma

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

Mucinous carcinoma of the colon: correlation of loss of mismatch repair enzymes with clinicopathologic features and survival

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