Dataset Information

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

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 (P_NED) 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. P_NED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff P_NED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher P_NED. 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.

SUBMITTER: Zou Y

PROVIDER: S-EPMC6441775 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Zou Yi Y Chen Linying L Wang Xingfu X Chen Yupeng Y Hu Liwen L Zeng Saifan S Wang Pengcheng P Li Guoping G Huang Ming M Wang Liting L He Shi S Li Sanyan S Jian Lihui L Zhang Sheng S

Journal of gastric cancer 20190320 1

<h4>Purpose</h4>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.<h4>Materials and methods</h4>Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis ...[more]

PMID: 30944765

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Project description:ObjectivesGastric neuroendocrine carcinoma (GNEC) is a class of rare histological subtypes in gastric cancer (GC). This retrospective case-control study aimed to explore the clinicopathological features and overall survival (OS) of patients with GNEC.MethodsA large population of GNEC and intestinal-type GC (IGC) patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The 1:1 propensity score matching (PSM) analysis was initiated to adjust the confounders between GNEC and IGC cohorts. Kaplan-Meier (KM) plots with log-rank tests were used to compare the survival differences in GNEC versus IGC. Additionally, Cox proportional hazard regression models were adopted to characterize the prognostic factors relevant to OS of the GNEC patients.ResultsAn entity of 4596 patients were collected, including 3943 (85.8%) IGC patients and 653 (14.2%) GNEC patients. The PSM analysis well-balanced all confounders in GNEC versus IGC (all P > .05). The KM plots showed that GNEC had significantly superior OS to IGC both before and after PSM analysis. Before PSM, the median OS was 52 (33.6-70.4) months in GNEC versus 32 (29.3-34.7) months in IGC (P = .0015). After PSM, the median OS was 26 (18.3-33.7) months in GNEC versus 21 (17.7-24.3) months in IGC (P = .0039). Stratified analysis indicated that GNEC had superior survivals to IGC in early stage patients and those who received surgery. In Cox regression analysis, age ≥ 60, tumor size > 50 mm, stage II-IV, T2, and N3 were independent risk factors for the GNEC patients (hazard ratio [HR]>1, P < .05). By contrast, year 2010 to 2015, female, and surgery were independent protective factors for these patients (HR < 1, P < .05).ConclusionsGNEC has unique clinicopathological features quite different from IGC and may have a superior survival to IGC in early stage patients. The prognostic factors identified here may assist the clinicians to more individually treat these patients.

Project description:BackgroundThe switch/sucrose nonfermentable (SWI/SNF) complex is an evolutionarily conserved chromatin remodeling complex that displays dysfunction in many tumors, especially undifferentiated carcinoma. Cancer stem cells (CSC), a special type of undifferentiated cancer cells with stem cell-like properties, play an essential role in tumor cell proliferation, invasion, and metastasis. In undifferentiated gastric carcinomas, the association of SWI/SNF complexes with clinicopathological features, CSC phenotype, and the prognosis is not fully understood.MethodsWe collected a cohort of 21 patients with undifferentiated/dedifferentiated gastric carcinoma. We next performed immunohistochemistry staining for the five subunits of the SWI/SNF complex (ARID1A, ARID1B, SMARCA2, SMARCA4, and SMARCB1), and four mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), as well as other markers such as p53, PD-L1, and cancer stem cell (CSC) markers (SOX2, SALL4). Then, we investigated the correlation of SWI/SNF complex subunits with clinicopathological characters and performed prognostic analysis.ResultsWe observed SMARCA2 loss in 12 cases (57.14%), followed by ARID1A (5 cases, 23.81%) and SMARCA4 (3 cases, 14.29%). Fourteen cases (66.67%) lost any one of the SWI/SNF complex subunits, including 3 cases with SMARCA2 and ARID1A co-loss, and 3 cases with SMARCA2 and SMARCA4 co-loss. Correlation analysis revealed that the CSC phenotype occurred more frequently in the SWI/SNF complex deficient group (P = 0.0158). Survival analysis revealed that SWI/WNF complex deficiency, undifferentiated status, CSC phenotype, and the loss of SMARCA2 and SMARCA4 resulted in worse survival. Univariate and multivariate Cox regression analyses screened out three independent factors associated with worse prognosis: undifferentiated status, SWI/SNF complex deficiency, and lymph node metastasis.ConclusionsThe SWI/SNF complex deficiency was more likely to result in a CSC phenotype and worse survival and was an independent prognostic factor in undifferentiated/dedifferentiated gastric carcinoma.

Dataset Information

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

Purpose

Materials and methods

Results

Conclusions

Publications

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

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