p53 and Rb immunohistochemistry staining reveal subtypes of gastric neuroendocrine carcinoma with distinct prognosis.

Authors

null

Jiazhang Xing

Peking Union Medical College Hospital, Beijing, China

Jiazhang Xing , Jingci Chen , Tingting You , Tao Lu , Huanwen Wu , Chunmei Bai , Zhao Sun , Yuejuan Cheng

Organizations

Peking Union Medical College Hospital, Beijing, China, Department of Pathology, Peking Union Hospital, Beijing, Dongchen Distric, China, Department of Oncology, Peking Union Medical College Hospital, Beijing, China

Research Funding

No funding received

Background: Due to the rarity, research on gastric neuroendocrine carcinoma (NEC) is limited. The treatment has been extrapolated from small-cell lung cancer (SCLC) data. However, a previous study found gastric NECs had a genetic feature characterized by a lower frequency of RB1 mutations than SCLC. Several studies also showed RB1mutation or loss of Rb expression could predict the efficacy of SCLC treatment in NEC. Our study investigated a subtyping method by p53 and Rb immunohistochemistry (IHC) staining in gastric NEC, which might help identify patients responding to SCLC treatment. Methods: Patients with gastric NEC who underwent radical surgery in Peking Union Medical College Hospital (PUMCH) from 2013 to 2021 were identified. The expression of Rb, p53, PD-L1 and CD8 T cell infiltration were accessed by IHC stain. The mutations of RB1 and TP53, tumor mutation burden (TMB), and microsatellite instability (MSI) were detected by whole-exom sequencing (WES). Fisher’s exact test and Mann–Whitney test were used to detect differences between groups. Spearman's test was used to detect correlations between variables. Kaplan-Meier and Cox hazards methods were applied to the survival analysis. Samples of gastric adenocarcinoma, gastric neuroendocrine tumor (NET), and SCLC were also included. Results: A total of 41 patients with gastric NEC were included. WES was carried out in 28 patients. TP53 mutation was detected in 14 patients. RB1 mutation was detected in 1 patient. A classification method based on gene mutation was not able to be further investigated. In IHC of 41 patients, 46.2% showed Rb expression absence. 68.4% had abnormal p53 expression. 39 patients were classified based on IHC results. Patients with both abnormal expression of p53 and Rb were defined as SCLC-like type, accounting for 38.5%.The remaining patients were defined as non-SCLC-like type. SCLC-like gastric NEC had an increased number of lymph nodes metastasis (P = 0.001) and higher TNM stage (P < 0.001). The SCLC-like group's overall survival (OS) was significantly lower than the non-SCLC-like group (P = 0.023). Classification based on p53 and Rb expression was an independent predictor of OS (P = 0.021), HR = 4.690, 95%CI (1.263, 17.421). The classification results of gastric NEC were significantly different from those in gastric NET(P = 0.001), gastric adenocarcinoma(P = 0.002), but not in SCLC(P = 0.464). In 39 classified patients, the positive rate of PD-L1 expression was 23.1%; CD8 T cells high infiltration (>25 % of the stromal area) was 46.7%; the median TMB was 4.9 Muts/MB, and MSI was not detected. There was no significant difference in the expression of immunotherapy-related markers between the two types. Conclusions: Our study revealed subtypes of gastric NEC based on p53 and Rb expression with different prognoses. Further research on the treatment efficacy predictive role of this subtyping method is warranted.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Neuroendocrine/Carcinoid

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr e16210)

DOI

10.1200/JCO.2022.40.16_suppl.e16210

Abstract #

e16210

Abstract Disclosures

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