Oncotarget

Clinical Research Papers:

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

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

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Oncotarget. 2017; 8:7025-7038. https://doi.org/10.18632/oncotarget.12347

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Abstract

Shiv Ram Krishn1, Sukhwinder Kaur1, Yuri M. Sheinin2, Lynette M. Smith3, Shailendra K. Gautam1, Asish Patel4, Maneesh Jain1, Vasthala Juvvigunta5, Priya Pai1, Audrey J. Lazenby2, Hemant K. Roy7 and Surinder K. Batra1,2,6

1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA

2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

3 Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, USA

4 Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA

5 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA

6 Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA

7 Department of Gastroenterology, Boston Medical Center, Boston, Massachusetts, USA

Correspondence to:

Surinder K. Batra, email:

Sukhwinder Kaur, email:

Keywords: mucins, hyperplastic polyps, sessile serrated adenoma/polyps, tubular adenomas, O-glycans

Received: August 12, 2016 Accepted: September 20, 2016 Published: September 29, 2016

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.


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