Hironori Aoki, MD, PhD1, Eiichiro Yamamoto, MD, PhD2, Akira Takasawa, MD, PhD2, Hiro-o Yamano, MD, PhD2, Taku Harada, MD, PhD1, Tamotsu Sugai, MD, PhD3, Hiromu Suzuki, MD, PhD2
1Sapporo Medical University / Teine-Keijinkai Hospital, Sapporo, Hokkaido, Japan; 2Sapporo Medical University, Sapporo, Hokkaido, Japan; 3Iwate Medical University, Morioka, Iwate, Japan
Introduction: Colorectal serrated lesions (SLs) include hyperplastic polyp (HP), traditional serrated adenoma (TSA) and sessile serrated adenoma/polyp (SSA/P). SSA/Ps are well known precursors of colorectal cancer (CRC) characterized by BRAF mutation and microsatellite instability (MSI). However, clinical and molecular characteristics of TSAs are not fully understood. We have reported that epigenetic silencing of SMOC1 is associated with development of traditional serrated adenomas (TSAs) and that SMOC1 may play a role in neoplastic pathways in TSAs and conventional adenomas (1). We aimed to clarify the clinical usefulness of SMOC1 in colorectal tumors.
Methods: Expression of SMOC1 was analyzed in a series of 127 colorectal tumors and adjacent normal colonic mucosa by immunohistochemistry (IHC). The staining intensity of SMOC1 was assessed as strong (3), moderate (2), weak (1) or negative (0). The proportions of positively stained tumor cells were assessed as 0 to 10 for each staining intensity. Because neoplasm heterogeneity caused varying degrees of immunoreactivity in respective specimens, we used the sum of each intensity × proportion as an IHC score (e.g., intensity × proportion = (3) × 5 + (2) × 3 + (1) × 1 + (0) × 1 = IHC score 22, scale of 0 to 30).
Results: Our IHC analysis revealed that SMOC1 is abundantly expressed in normal colon, HPs and SSA/Ps, while it was significantly downregulated in TSAs, high-grade adenomas and CRCs. Among serrated lesions, SMOC1 is expressed in HPs, SSA/Ps and SSA/Ps with CRC, while it was significantly downregulated in TSAs and TSAs with CRC. Notably, in TSAs which consisted of flat and protruding subcomponents, SMOC1 expression levels were lower in the protruding portions than those in the flat portions (p < 0.001).
Discussion: These results suggest that downregulated expression of SMOC1 could be a hallmark of TSAs and conventional adenomas at high risk of developing CRC.
(1) Aoki H, Yamamoto E, Takasawa A et al. Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer. Oncotarget. 2017: 4707-4721
Citation: Hironori Aoki, MD, PhD; Eiichiro Yamamoto, MD, PhD; Akira Takasawa, MD, PhD; Hiro-o Yamano, MD, PhD; Taku Harada, MD, PhD; Tamotsu Sugai, MD, PhD; Hiromu Suzuki, MD, PhD. P1025 - CLINICAL USEFULNESS OF SMOC1 AS A DIAGNOSTIC MARKER FOR COLORECTAL SERRATED LESIONS AND COLORECTAL PRECANCEROUS LESIONS. Program No. P1025. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.