TY - JOUR
T1 - Agrin in the Muscularis mucosa serves as a biomarker distinguishing hyperplastic polyps from sessile serrated lesions
AU - Rickelt, Steffen
AU - Condon, Charlene
AU - Mana, Miyeko
AU - Whittaker, Charlie
AU - Pfirschke, Christina
AU - Roper, Jatin
AU - Patil, Deepa T.
AU - Brown, Ian
AU - Mattia, Anthony R.
AU - Zukerberg, Lawrence
AU - Zhao, Qing
AU - Chetty, Runjan
AU - Lauwers, Gregory Y.
AU - Neyaz, Azfar
AU - Leijssen, Lieve G.J.
AU - Boylan, Katherine
AU - Yilmaz, Omer H.
AU - Deshpande, Vikram
AU - Hynes, Richard O.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2020/3/15
Y1 - 2020/3/15
N2 - Purpose: Sessile serrated lesions (SSL) are precursors to colon carcinoma, and their distinction from other polyps, in particular hyperplastic polyps (HP), presents significant diagnostic challenges. We evaluated expression patterns in colonic polyps of previously identified colon carcinoma-associated extracellular matrix (ECM) proteins to identify markers distinguishing SSLs from other polyps. Experimental Design: Gene-expression analyses of ECM proteins were performed using publicly available data on preneoplastic colonic polyps. In parallel, we evaluated by IHC the expression of agrin (AGRN) in over 400 colonic polyps, including HP, SSL with and without dysplasia, traditional serrated adenomas (TSA), and tubular adenomas (TA), and compared the consistency of standard histologic diagnosis of SSLs by experienced gastrointestinal pathologists with that of AGRN IHC. Results: Differential gene expression analysis and IHC identified AGRN, serine peptidase inhibitor (SERPINE2), and TIMP metallopeptidase inhibitor 1 (TIMP1) elevated in SSLs and HPs but decreased in TAs and absent in normal colon. AGRN-positive basal laminae were noted in all TA, TSA, HP, and SSL in distinguishable patterns, whereas other polyps and normal mucosa were negative. SSL with or without dysplasia consistently showed IHC staining for AGRN in the muscularis mucosae, which was absent in HP, TSA, TA, and other polyps. In contrast, histologic evaluation showed only weak interobserver agreement (kappa value ¼ 0.493) in distinguishing SSLs. Conclusions: Muscularis mucosae-based AGRN immunostaining is a novel biomarker to distinguish SSL from HP, TSA, and TA, with a specificity of 97.1% and sensitivity of 98.9% and can assist in diagnosis of morphologically challenging colonic polyps.
AB - Purpose: Sessile serrated lesions (SSL) are precursors to colon carcinoma, and their distinction from other polyps, in particular hyperplastic polyps (HP), presents significant diagnostic challenges. We evaluated expression patterns in colonic polyps of previously identified colon carcinoma-associated extracellular matrix (ECM) proteins to identify markers distinguishing SSLs from other polyps. Experimental Design: Gene-expression analyses of ECM proteins were performed using publicly available data on preneoplastic colonic polyps. In parallel, we evaluated by IHC the expression of agrin (AGRN) in over 400 colonic polyps, including HP, SSL with and without dysplasia, traditional serrated adenomas (TSA), and tubular adenomas (TA), and compared the consistency of standard histologic diagnosis of SSLs by experienced gastrointestinal pathologists with that of AGRN IHC. Results: Differential gene expression analysis and IHC identified AGRN, serine peptidase inhibitor (SERPINE2), and TIMP metallopeptidase inhibitor 1 (TIMP1) elevated in SSLs and HPs but decreased in TAs and absent in normal colon. AGRN-positive basal laminae were noted in all TA, TSA, HP, and SSL in distinguishable patterns, whereas other polyps and normal mucosa were negative. SSL with or without dysplasia consistently showed IHC staining for AGRN in the muscularis mucosae, which was absent in HP, TSA, TA, and other polyps. In contrast, histologic evaluation showed only weak interobserver agreement (kappa value ¼ 0.493) in distinguishing SSLs. Conclusions: Muscularis mucosae-based AGRN immunostaining is a novel biomarker to distinguish SSL from HP, TSA, and TA, with a specificity of 97.1% and sensitivity of 98.9% and can assist in diagnosis of morphologically challenging colonic polyps.
UR - http://www.scopus.com/inward/record.url?scp=85081945914&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081945914&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-2898
DO - 10.1158/1078-0432.CCR-19-2898
M3 - Article
C2 - 31852835
AN - SCOPUS:85081945914
SN - 1078-0432
VL - 26
SP - 1277
EP - 1287
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -