418P - Expression of mTOR pathway components in gastric neuroendocrine neoplasms

Abstract

Background

Gastric neuroendocrine neoplasms (gNENs) are a heterogeneous group of tumors showing different clinicopathological features and behavior. PI3K/AKT/mTOR pathway is activated in various types of neoplasms. The mTOR signaling pathway plays a key role in the control of protein synthesis as well as regulation of cell proliferation and neuroendocrine tumor (NET) growth. Expression of mTOR cascade components in gNENs, however, has not been fully explored. This study aimed to assess the expression of mTOR and its two major effectors in the spectrum of gNENs and to correlate expression levels with clinicopathological variables and prognosis.

Methods

Immunohistochemistry (IHC) was performed to assess the expression of phosphorylated forms of mTOR and its major effectors 4E-BP1 and p70S6K in 45 surgically resected gNENs, including 15 carcinoids of type 1, 9 NETs of type 3, and 21 poorly differentiated NECs (5 carcinomas of small cell type and 16 carcinomas of large cell type).

Results

Positive p-mTOR, p-4E-BP1, and p-p70S6K immunostaining was seen in 29 (64.4%), 31 (68.9%), and 20 (44.4%) of 45 examined gNENs, respectively. Distribution of mTOR and its downstream components was heterogeneous among the various gNEN types, with both cytoplasmic and nuclear staining patterns identified. Strong expression of phosphorylated mTOR, 4E-BP1 and p70S6K was detected in type I, type III tumors and high-grade carcinomas of either large or small cell types. The IHC score of p-mTOR and p-4E-BP1 was higher but not significantly in G3 carcinomas than in G1/G2 tumors. Strong p70S6K staining was significantly more frequent in high grade neoplasms than in well differentiated tumors (p 0.027). Preliminary evaluation did not reveal correlation of marker expression levels in tumors with clinicopathological features or prognosis.

Conclusions

These data shows that the components of the mTOR pathway are highly expressed in the different types of gastric neuroendocrine neoplasms, suggesting that mTOR-targeted therapy may play a role in the treatment of these tumors. The prognostic value of the mTOR effectors should be further evaluated.

Clinical trial indentification

Legal entity responsible for the study

N.N. Blokhin Russian Cancer Research Center, 115478, Moscow, Russian Federation

Funding

N.N. Blokhin Russian Cancer Research Center, 115478, Moscow, Russian Federation

Disclosure

All authors have declared no conflicts of interest.