Mucinous and Signet Ring Cell Differentiation Affect Patterns of Metastasis in Colorectal Carcinoma and Influence Survival

Abstract

Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis ( P< .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement ( P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival ( P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.

Survival difference between mucinous vs. non-mucinous colorectal cancer following cytoreductive surgery and intraperitoneal chemotherapy

“…Mucinous tumors tended to have higher PCI. Kermanshahi et al have demonstrated previously that mucinous tumors are less likely to develop liver metastasis and more likely to develop peritoneal disease [25]. A recent study of a Dutch cohort has shown colorectal cancer peritoneal metastases to be enriched for the consensus molecular subtype (CMS) four or the mesenchymal subtype.…”

Signet ring cell colorectal cancer: genomic insights into a rare subpopulation of colorectal adenocarcinoma

“…5 In the previous studies, SRCC has been associated with younger age, advanced tumour stage at presentation and lymph node metastasis, 2 , 6 – 8 and SRCC has significantly poorer prognosis compared to that of adenocarcinomas. 6 , 9 – 14 Several studies have suggested a higher rate of microsatellite instability and BRAF gene mutation in SRCC. 7 , 15 – 17 However, the sample sizes in those studies were generally small, and most evaluated only single gene mutation.…”

Differentiating breast carcinoma with signet ring features from gastrointestinal signet ring carcinoma: assessment of immunohistochemical markers

“…Tumors arising from both breast and the GI tract may metastasize to other similar locations [9]. For example, both lobular breast and gastric signet-ring carcinomas are recognized to cause peritoneal carcinomatosis and show similar patterns of infiltrative growth [10]. Given this overlap in locations and morphology, the distinction between these tumors is an important diagnostic challenge as the available management options depend on identification of the primary site.…”