Original ArticlesChromogranin A Expression in Rectal Neuroendocrine Tumors Is Associated With More Aggressive Clinical Behavior and a Poorer PrognosisKim, Jisup MD*; Kim, Joo Young MD, PhD†; Oh, Eun Hye MD‡,§; Yoo, Changhoon MD, PhD∥; Park, In Ja MD, PhD¶; Yang, Dong-Hoon MD, PhD‡; Ryoo, Baek-Yeol MD, PhD∥; Ryu, Jin-Sook MD, PhD#; Hong, Seung-Mo MD, PhD*Author Information Departments of *Pathology ‡Gastroenterology ∥Oncology ¶Colon and Rectal Surgery #Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine †Department of Pathology, Nowon Eulji Medical Center, Eulji University, Seoul §Department of Gastroenterology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea Presented in part at the 17th Annual ENETS Conference, March 11-13, 2020, Barcelona, Spain. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Seung-Mo Hong, MD, PhD, Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea (e-mail: [email protected]). The American Journal of Surgical Pathology: November 2020 - Volume 44 - Issue 11 - p 1496-1505 doi: 10.1097/PAS.0000000000001526 Buy Metrics Abstract Although rectal neuroendocrine tumors (NETs) with an L-cell phenotype and small size are generally less clinically serious, the new 2019 World Health Organization (WHO) classification system has categorized all of these lesions as malignant. Identifying biomarkers of rectal NETs is thus important for stratifying their clinical behavior. Chromogranin A protein expression was assessed in 538 endoscopically or surgically resected rectal NETs and compared with clinicopathologic factors to identify its clinical and prognostic significance. All of the rectal NETs analyzed (100%) were synaptophysin positive, but chromogranin A labeling was only detected in 111 cases (20.6%). Chromogranin A expression in the rectal NETs was more commonly associated with older age (50 y and older; P=0.013), male sex (P=0.002), radical resection (P=0.003), large tumor size (≥1 cm; P=0.038), muscularis propria invasion (P=0.002), lymphovascular (P=0.014) and perineural (P<0.001) invasion, an involved resection margin (P=0.028), and lymph node metastasis (P=0.003). Patients with chromogranin A expression had higher plasma chromogranin A levels (P=0.023) than those without chromogranin A expression during follow-up. The 10-year disease-free survival rate in rectal NET patients with chromogranin A expression (91.5%) was significantly shorter than the negative cases (99.7%) by both univariate (hazard ratio=14.438; 95% confidence interval: 2.911-71.598; P<0.001) and multivariate (hazard ratio=12.099; 95% confidence interval, 2.044-71.608; P=0.006) analyses. In summary, rectal NETs that are positive for chromogranin A are less common than those with synaptophysin expression and show more aggressive clinical behavior. Chromogranin A is therefore a prognostic indicator of higher recurrence risk in patients with endoscopically or surgically resected rectal NETs. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.