Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance.

Lynette M Smith,Maneesh Jain,Vasthala Juvvigunta,Sukhwinder Kaur,Audrey J Lazenby,Hemant K Roy,Priya Pai,Surinder K Batra,Shiv Ram Krishn,Shailendra K Gautam,Asish Patel,Yuri M Sheinin

doi:10.18632/oncotarget.12347

Abstract

Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066), elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in SSA/P cases in comparison to HP cases. Interestingly, significantly higher number of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well as filled the crypt lumen compared to only goblet cells in majority of the HP cases. Improved diagnostic potential was revealed by multivariate logistic regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19-9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and 97%/83%, respectively. Overall, the mucin and associated O-glycan based panel defined in the present study could aid in discriminating SSA/P from HP to devise better colon surveillance strategies.

Highlights

Colorectal cancer (CRC) is a molecularly and histologically heterogeneous, biologically diverse public health problem with over one million new cases diagnosed worldwide every year [1]
Considering the high clinical utility of the appropriate polyp classification, in this study, we evaluated the potential of colonic mucins (MUC1, MUC4, MUC17, MUC2, MUC5AC, and MUC6) and associated glycans (Tn/STn-MUC1 and CA19-9) for differentiating sessile serrated adenoma/polyps (SSA/P) from hyperplastic polyps (HP) and tubular adenoma (TA)
Our earlier findings indicated a differential expression of mucins and their associated O-glycans during the progression of CRC and we demonstrated their utility in differentiating benign lesions from precancerous and cancerous ones [22]

Summary

Introduction

Colorectal cancer (CRC) is a molecularly and histologically heterogeneous, biologically diverse public health problem with over one million new cases diagnosed worldwide every year [1]. According to the latest World Health Organization criteria, the heterogeneous group of serrated lesions is pathologically classified as hyperplastic polyps (HP), sessile serrated adenoma/polyps (SSA/P) and traditional serrated adenomas (TSA) [8]. Epidemiology studies of large cohorts suggest that a stepwise progression of dysplasia and carcinoma from SSA/P may take 10 to 15 years [12] ; there are case reports that suggest faster neoplastic progression [13] or progression taking place in as little as eight months [10, 14, 15]

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Conclusion