Signet ring cell differentiation in mucinous colorectal carcinoma

Börger, M. Elisa; Gosens, Marleen J.E.M.; Jeuken, Judith; Kempen, Léon C van; Velde, C.J.H. van de; Krieken, J.H.J.M. van; Nagtegaal, Irıs D.

doi:10.1002/path.2181

Cited by 93 publications

(91 citation statements)

References 30 publications

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“…The negative prognostic effect of MA becomes more readily apparent when the adverse effects are minimal in the low-risk group. In accordance with the molecular background, low expression of the adhesion molecules, such as E-cadherin and β-catenin may result in reduced cell adhesion in regions of high mucinous content and may promote scattering of cancer cells, further leading to local recurrence, distant metastasis and poor prognosis [25,26]. These findings are supported by another cohort [27] in which a preponderance of local relapse was observed.…”

Section: Discussionsupporting

confidence: 75%

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

et al. 2018

Cell Physiol Biochem

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Background/Aims: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. Methods: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. Results: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. Conclusion: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.

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Section: Discussionsupporting

confidence: 75%

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

et al. 2018

Cell Physiol Biochem

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“…We failed to detect increased ALK expression by IHC in any of the 42 cases tested in this study, including the single case that was positive by FISH. The failure to show ALK overexpression in the FISH positive case could be due to the discohesive nature of signet ring cancers leading to relatively scanty amount of cellular material against a broad infiltrative stroma [Borger et al 2007]. …”

Section: Discussionmentioning

confidence: 99%

Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract

et al. 2015

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Objectives: ALK-EML4 translocation is an established driver aberration in non-small cell lung cancer (NSCLC), with reported predilection for cases with signet ring histology. We assessed the presence of anaplastic lymphoma kinase (ALK) gene rearrangements in signet ring cancers arising in the stomach and colon. Methods: Histologically confirmed cases of signet ring adenocarcinoma of the stomach or the colon were identified. The presence of the classic ALK and EML4 fusion gene was initially determined by fluorescence in-situ hybridization (FISH) technique. Immunohistochemistry (IHC) was performed using two previously validated antibodies, ALK1 clone (1:100; DAKO) and 5A4 (Novocastra, Leica Biosystems) along with positive controls of ALK-translocated lung cancer. Results: We employed 42 cases of signet ring carcinoma diagnosed between 2001 and 2011; 25 gastric and 17 colon cancer. Median age 63.3 years; male/female 17/25; race, black 47.5%, white 47.5%, others, 5%; stage I, 21.4%; stage II, 31%; stage III, 26.2%; stage IV, 21.4%. One of 42 cases (2.3%) was positive for ALK translocation by FISH using the standard criteria of at least 15% positive cells for the break-apart signal (50-70 cells enumerated per case). Using a less restrictive cut-off of 10% positive cells, 7 cases (16%) were considered possibly positive. None of the 'possibly positive' cases was found to harbor ALK translocation by another molecular testing approach (IHC). IHC with two previously validated monoclonal antibodies showed 0 of 42 (0%) cases positive. Conclusions: ALK gene rearrangement is very rare in gastrointestinal cancers and enrichment strategy focusing on signet ring cell histology did not significantly improve the detection rate.

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“…However, the signet-ring cell component was not an independent predictor of poor outcome in multivariate analysis of mucinous adenocarcinoma. Borger et al 14 reported that the presence of signet-ring cells in mucinous adenocarcinoma correlated with increased T-stage and poor prognosis and these cells showed disruption of the E-cadherin/b-catenin complex. Signetring cells are usually present as single cells or in loose clusters, which implies a disruption in cell-cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

“…This could explain their aggressive behavior with regard to invasion and metastasis. Borger et al 14 reported that the presence of signet-ring cells in mucinous adenocarcinoma correlated with increased T-stage and poor prognosis. In the current practice of pathology, there is no definitive rule on how to report a minor component of signet-ring cells in colorectal mucinous adenocarcinomas.…”

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confidence: 99%

Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma

et al. 2008

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Mucin occasionally accumulates intracellularly in colorectal mucinous adenocarcinomas, resulting in signetring cell morphology. In the current practice of pathology, there is no definitive rule on how to report a minor component of signet-ring cells in colorectal mucinous adenocarcinomas. We hypothesized that the absence of signet-ring cell component might have a favorable effect on survival of mucinous adenocarcinoma patients. To assess the biological characteristics of colorectal mucinous adenocarcinoma, we analyzed its clinicopathological features, microsatellite instability status, and survival outcomes and compared them with those of colorectal signet-ring cell carcinoma. A total of 266 consecutive colorectal mucinous adenocarcinoma patients and 65 signet-ring cell carcinoma patients were included. Mucinous adenocarcinomas, by comparison with signet-ring cell carcinomas, were characterized by development at an older age, less frequent vascular invasion and lymph node metastasis, and lower TNM stage at presentation. A total of 21 (22%) of 95 mucinous adenocarcinomas and 12 (19%) of 63 signet-ring cell carcinomas were high-frequency microsatellite instability. Patients with mucinous adenocarcinoma had significantly better survival than those with signet-ring cell carcinoma (Po0.0001) or than those with signet-ring cell carcinoma showing 450% extracellular mucin by volume (Po0.0001). In univariate analysis, absence of signet-ring cell component (P ¼ 0.0197), absence of vascular invasion, decreased invasion depth, no lymph node metastasis, and lower TNM stage had a favorable effect on survival of mucinous adenocarcinoma patients. Absence of vascular invasion, no lymph node metastasis, and lower TNM stage had a favorable effect on survival of signet-ring cell carcinoma patients. Multivariate analysis showed that higher TNM stage and T stage 4 were independent predictors of poor outcome in patients with mucinous adenocarcinoma. Our observations strongly suggest that pathologists should report the percentage of signet-ring cell component in colorectal mucinous adenocarcinomas and mucinous adenocarcinoma has different biologic behavior compared with signet-ring cell carcinoma. Modern Pathology (2008Pathology ( ) 21, 1533Pathology ( -1541 doi:10.1038/modpathol.2008 published online 10 October 2008 Keywords: colorectal mucinous adenocarcinoma; signet-ring cell; survival Although colorectal adenocarcinoma has a relatively better prognosis than other gastrointestinal malignancies with the same stage, specific histological types of colorectal carcinoma such as mucinous adenocarcinoma and signet-ring cell carcinoma have a poor prognosis. 1-3 Colorectal mucinous adenocarcinoma and signet-ring cell carcinoma are adenocarcinomas in which the cancer cells produce excess mucin. A unique pathologic feature of signet-ring cell carcinoma is the presence of signetring cells, which are single tumor cells with intracytoplasmic mucin that displaces their nuclei. The infiltrating cells spread diffusely throughout the bowel wall. I...

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Signet ring cell differentiation in mucinous colorectal carcinoma

Cited by 93 publications

References 30 publications

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract

Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma

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