Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells

Abstract

Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (Po0.0001) and lymph node metastasis (Po0.0001), higher pathological T and tumor node metastasis stages (P ¼ 0.047 and P ¼ 0.001), and more frequent SOX2 (P ¼ 0.038) and NOTCH3 expressions (P ¼ 0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%, Po0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (Po0.0001) and multivariate (P ¼ 0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma. Modern Pathology (2013Pathology ( ) 26, 1123Pathology ( -1131 doi:10.1038/modpathol.2012 published online 12 October 2012 Keywords: colorectum; micropapillary carcinoma; prognosis; stem cell marker; TNM stage Colorectal cancer is one of the leading causes of cancer deaths worldwide, and both the prevalence and the incidence rate in South Korea are rapidly rising. 1 For metastatic colorectal cancer, the 5-year survival rate is only about 10%. 2 Micropapillary carcinoma is a relatively uncommon and distinctive tumor characterized by small clusters of tumor cells in the clear lacunar spaces, mimicking lymphatic or vascular channels. 3 Micropapillary carcinoma has high potential to metastasize to the regional l...

The Role of Notch3 in Cancer

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Expression of the cancer stem cell markers CD44v6 and ABCG2 in tongue cancer: Effect of neoadjuvant chemotherapy on local recurrence

“…Alternative splicing of exons 6-15 (variant exons 1-10) gives rise to numerous variant forms of CD44 (CD44v), in which an additional segment encoded by one or more of the variant exons is inserted in the extracellular domain of CD44s, which is encoded by exons 1-5 and exons 16-20 (16,42,43). The variant 6 isoform (CD44v6), in particular, is associated with several cancer types but not in somatic cells (15,(18)(19)(20)(21). Moreover, CD44v6 is widely known as a marker of CSCs (18,21,36,(44)(45)(46).…”

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

“…In addition, the importance of SOX2 in cancer metastasis has also been addressed. Previously, several studies demonstrated that SOX2 expression was closely associated with lymph node metastasis, distant spread and poor prognosis in colorectal carcinoma patients (6,90,91). Certain data suggested that SOX2 knockdown may induce mesenchymal-epithelial transition (MET).…”