Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study

Abstract

Purpose: As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.

Materials and methods: We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.

Results: Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.

Conclusion: The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

Keywords: Gastro-enteropancreatic neuroendocrine tumor; Incidence; Pathology; Prognosis.

Fig. 1

Distribution of 4,951 gastroenteropancreatic neuroendocrine tumors according to the organ system.

Fig. 2

Distribution of gastroenteropancreatic neuroendocrine tumors according to diagnosis by 2000 and 2010 classification.WDET, well-differntiated endocrine tumor; WDEC, well-differentiated endocrine carcinoma; PDEC, poorly differentiated endocrine carcinoma/small cell carcinoma; MEEC, mixed exocrine-endocrine carcinoma; MEC, metastatic endocrine carcinoma; NET, neuroendocrine tumor; NEC, neuroendocrine carcinoma.

Fig. 3

Site distribution of gastroenteropancreatic neuroendocrine tumors in Korea according to the 2000 WHO classification. The most common tumor is WDET in rectum. WHO, World Health Organization; WDET, well-differntiated endocrine tumor; MEC, metastatic endocrine carcinoma, MEEC, mixed exocrine-endocrine carcinoma; PDEC, poorly differentiated endocrine carcinoma/small cell carcinoma; WDEC, well-differentiated endocrine carcinoma.

Fig. 4

Changes in incidence of gastroenteropancreatic neuroendocrine tumors in Korea during the last decade according to the number of annual diagnosis.

Fig. 5

Changes in annual incidence of gastroenteropancreatic neuroendocrine tumors in each site during the last decade.

Fig. 6

Changes in incidence of gastroenteropancreatic neuroendocrine tumors in Korea during the last decade according to the 2000 WHO classification of tumors. WHO, World Health Organization; WDET, well-differntiated endocrine tumor;WDEC, well-differentiated endocrine carcinoma; PDEC, poorly differentiated endocrine carcinoma/small cell carcinoma; MEEC, mixed exocrine-endocrine carcinoma; MEC, metastatic endocrine carcinoma.

Fig. 7

Site distribution of gastroenteropancreatic neuroendocrine tumors according to the survival. Mean survival time is the longest in stomach neuroendocrine tumor (154.42±7.74 months) and the shortest in biliary tract neuroendocrine tumors (44.32±6.02 months). Disease related death is most common in hepatobiliary tract.

Fig. 8

Five- and 10-year survival rate according to the 2000 (A) and 2010 WHO classification of NET (B). According to the 2000 WHO classification, the difference of 10 year survival rate between NET G1 and NET G2 is more distinct than the difference between WDET and WDEC. WHO, World Health Organization; NET, neuroendocrine tumor; WDET, well-differntiated endocrine tumor; WDEC, well-differentiated endocrine carcinoma; PDEC, poorly differentiated endocrine carcinoma/small cell carcinoma; MEEC, mixed exocrine-endocrine carcinoma; MEC, metastatic endocrine carcinoma; NEC, neuroendocrine carcinoma.