Impact of Chromogranin A Expression on Disease Characteristics and Prognosis in Rectal Neuroendocrine Tumors

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In a single-institution Korean study reported in the American Journal of Surgical Pathology, Kim et al found that chromogranin A expression in rectal neuroendocrine tumors is associated with more aggressive clinical characteristics and poorer prognosis.

As stated by the investigators, “Although rectal neuroendocrine tumors with an L-cell phenotype and small size are generally less clinically serious, the new 2019 World Health Organization classification system has categorized all of these lesions as malignant. Identifying biomarkers of rectal neuroendocrine tumors is thus important for stratifying their clinical behavior.”

Study Details

The study involved pathology data from 538 eligible patients who had endoscopically (n = 480) or surgically resected (n = 58) well-differentiated rectal neuroendocrine tumors from an institutional pathology database who had been treated between 1994 and 2014.

Key Findings

All rectal neuroendocrine tumors were synaptophysin-positive. Chromogranin A labeling was detected in 111 cases (20.6%).

Chromogranin A expression was significantly associated with older age (≥ 50 years, P = .013), male sex (P = .002), radical resection (P = .003), large tumor size ( ≥ 1 cm, P = .038), muscularis propria invasion (P = .002), lymphovascular invasion (P = .014),  perineural invasion (P < .001), involved resection margin (P = .028), and lymph node metastasis (P = .003).

Among 71 patients with available data, those with chromogranin A expression had higher plasma chromogranin A levels vs those without chromogranin A expression during follow-up (mean = 101.3 ng/mL vs 60.5 ng/mL, P = .023).

Disease-free survival at 10 years was 91.5% among patients with chromogranin A expression vs 99.7% in those without expression (hazard ratio [HR] = 14.4, P < .001). The difference remained significant on multivariate analysis (HR = 12.1, P = .006), with chromogranin A expression being the only independent predictor of reduced disease-free survival. 

In univariate analyses of subgroups, 10-year disease-free survival was significantly reduced with chromogranin A expression among patients with grade 1 tumors (95.3% vs 99.7%, P = .011), grade 2 tumors (57.1% vs 100%, P = .001), large rectal neuroendocrine tumors ( ≥ 1 cm; 71.4% vs 96.6%, P = 0.017), and pT1 tumors (95.1% vs 100%, P = .001); none of the factors remained significant on multivariate analysis. 

The investigators concluded, “Rectal neuroendocrine tumors 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 neuroendocrine tumors.”

Seung-Mo Hong, MD, PhD, of the Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, is the corresponding author for the American Journal of Surgical Pathology article.

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