Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma

Abstract

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...

Adenocarcinoma of the Rectum in Patients Under Age 40 Is Increasing

“…signet-ring cell histology is known to be more aggressive because the cellular abnormality involves the lack of cell-to-cell adhesions, which results in greater spreading tendency. 8,9 this is reflected in our histologic comparison data and correlates with outcomes seen in other studies of colon and rectal cancers. 7,12 there is a rationale from the gastric cancer literature to suggest that signet-ring cell histology has an underlying genetic basis.…”

“…7,8 signet-ring cell adenocarcinoma histology is defined by a greater than 50% presence of tumor cells with prominent intracytoplasmic mucin accumulation and a lack of cellto-cell adhesion molecules. 9 in gastric adenocarcinoma, a link to e-cadherin CDh1 gene mutation has been shown to correlate with signet-ring cell histology, 10,11 which also tends to occur in younger patients.…”

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

“…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.…”

Predictors of Lymph Node Metastasis and Prognosis in pT1 Colorectal Cancer Patients with Signet-Ring Cell and Mucinous Adenocarcinomas

“…The aggressive behavior and reduced survival associated with SRC has been demonstrated by many previous studies, and many researchers attribute this phenomenon to a greater propensity of SRC histology to reach advanced stage, driven by the absence of the expression of adhesive molecules such as E-cadherin and β-catenin, which causes the tumor cells to have a more aggressive behavior and to disperse to other organs [20,21]. Our research demonstrated high prevalence of LNM of SRC in both colon and rectum tumor, while didn't find the adverse prognosis of SRC in colon cancer.…”