Prognostic relevance of histopathological features in signet ring cell carcinoma of the colorectum

Abstract

Signet ring cell carcinoma (SRCC) is a rare variant of colorectal cancer (CRC), by definition composed of at least 50 % of neoplastic cells showing signet ring cell morphology. Colorectal SRCC is mainly characterized by aggressive clinical behavior, high pTNM stage and microsatellite instability (MSI). We assessed the prognostic value of several histopathological parameters (histological grade, venous invasion, lymphovascular invasion, MSI, mucin content, tumour budding, pTNM stage) in terms of disease free survival (DFS) and cancer specific survival (CSS) in a series of 32 SRCCs. We confirm that pTNM stage at diagnosis is relevant for predicting DFS and CSS in SRCC. In addition, we show on haematoxylin and eosin or immunohistochemically stained (CD34, podoplanin) sections that venous invasion and lymphovascular invasion are significantly associated with shorter DFS and CSS in SRCC. Notably, venous invasion assed by immunohistochemistry had the highest risk ratio and proved to be the only independent prognostic variable. Finally, we show that histological grade, as assessed on the percentage of formed glands, has prognostic relevance in SRCC as high-grade tumours (<50 % of glands) had significantly shorter CSS compared to low-grade tumours. This remained an independent variable at multivariate analysis. If our findings are confirmed in further studies, venous invasion as assessed by immunohistochemistry and histological Tgrade might be added to guidelines for SRCC reporting as significant prognostic factors.

Keywords: CD34; Colorectal; Grade; Podoplanin; Poorly differentiated clusters; Signet ring; Venous invasion.