Objective: CpG island methylator phenotype (CIMP)-positive colorectal cancers (CRC) and CRC with microsatellite instability (MSI) were reported to have a decreased expression of estrogen receptor, beta1 (ER-β1), and methylation accompanied by decreased expression for the caudal-related homeobox, transcription factor 2 (CDX2). While precursor lesions of these cancers, known as sessile serrated adenomas (SSA), were found to have decreased CDX2 expression, the status of ER-β1 expression in SSA is unknown. The aim of this study is to determine ER-β1 expression in SSA and its relation to CDX2 expression.
Methods: Sections of formalin fixed and paraffin embedded tissue from 62 consecutive cases of SSA were stained by immunohistochemistry for ER-β1 and CDX2. SSA with ER-β1 or CDX2 expression similar to that of a normal colon were scored as 0, while those with a loss of expression in <10% of SSA crypts as 1, 11-25% as 2, 26-50% as 3, 51-75% as 4, and CDX2 loss in >75% of the SSA crypts scored as 5.
Results: There is a significant correlation between a loss of CDX2 and the loss of ER-β1 scores in SSA (p<0.001). The downregulation of CDX2 was greater in SSA arising from the right colon compared to the left colon and rectum (p=0.012). Similarly, downregulation of ER-β1 was greater in SSA arising in the right colon compared to the left colon and rectum (p=0.014).
Conclusions: Our findings show significant downregulation of both ER-β1 and CDX2 expression in SSA, especially in the right colon. These findings suggest that ER-β1 downregulation plays a significant role in the malignant progression of SSA.
© 2019 by the Association of Clinical Scientists, Inc.