J Gastric Cancer.  2019 Mar;19(1):121-131. 10.5230/jgc.2019.19.e9.

Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases

Affiliations
  • 1Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. zhgshg@126.com
  • 2Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3Public Security Bureau of Changle City, Changle, China.
  • 4Department of Pathology, No. 2 Hospital, Xiamen, China.
  • 5Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China.
  • 6Maternity and Child Care Hospital of Huli District, Xiamen, China.

Abstract

PURPOSE
The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications.
MATERIALS AND METHODS
Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters.
RESULTS
In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED.
CONCLUSIONS
GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.

Keyword

Stomach neoplasms; Adenocarcinoma; Neuroendocine tumors; Prognosis; Immunohistochemistry

MeSH Terms

Adenocarcinoma
Chromogranin A
Classification
Humans
Immunohistochemistry
Lymph Nodes
Neoplasm Metastasis
Neural Cell Adhesion Molecules
Prognosis
Stomach
Stomach Neoplasms
Synaptophysin
Chromogranin A
Neural Cell Adhesion Molecules
Synaptophysin
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