Abstract 892P
Background
The aberrant activation of Hh signaling pathway is implicated with carcinogenesis in different tumors. Several Hh inhibitors, as vismodegib, have demonstrated efficacy in some neoplasia, for example, basal cell carcinoma. We aim to study the Hh pathway in gastroenteropancreatic (GEP) NENs.
Methods
Retrospective study of GEP NENs diagnosed between 2014 and 2018 in Burgos University Hospital. We analysed in paraffin-fixed, paraffin-embedded (PFPE) samples Hh proteins by immunohistochemistry (IHC) and genes by Polymerase Chain Reaction (PCR). Finally, we performed a survival analysis with Kaplan Meier and Long rank test.
Results
We included 64pt. with a median age of 64 years. Based on the WHO classification 13pt. had a neuroendocrine carcinoma (NEC). Twenty-four (37.5%) had a stage IV and their median survival was 14.8 months (CI 95%, 0.0-38.5). The median follow-up was 42.9 months and the global mortality was 34%. The clinical characteristics are summarized in the table. Forty-six pt. (72%) showed protein expression by IHC and all the patients reveal mRNA of the genes by PCR. We found no difference in the expression of genes or proteins among stage, treatment, grade or localization. NENs stage IV who express Gli1 by IHC have poor prognosis: median survival 8.6 months (95% CI,3.5-13.7) vs 20.7 months (95% CI, 26.3-107.3), p=0.037. Gene expression of Snail and PTCH-1 in Stage IV NET are mutually exclusive (p<0.01). Table: 892P
| Characteristics | Results |
| Gender – no. (%) | 36 (56) 28 (44) |
| Stage – no. (%) Stage I, II and III Stage IV | 40 (63) 24 (38) |
| Localization – no. (%) Ileum, jejunum and duodenum | 12 (19) 9 (14) 43 (67) |
| Treatment first line – no. (%) Somatostatine analogues | 6 (27) 6 (27) 10 (45) |
| Protein expression – no. (%) | 19 (30) 18 (28) 4 (6) 0 (0) 8 (13) 5 (8) |
| Gene expression – no. (%) Snail | 57 (89) 60 (94) 24 (38) 61 (95) 64 (100) 40 (63) 60 (94) 60 (94) 60 (94) 60 (94) 6 (9) 60 (94) 6 (9) 6 (9) 58 (91) |
Conclusions
The Hh signaling pathway is activated in some patients with NENs and could be a potential target in the treatment of this patients. NEC G3 that express Gli1 have a worse prognosis. SNAIL and PTCH-1 are mutually exclusive in stage IV NET, suggesting different ways of activating the Hh signaling pathway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
SACYL.
Disclosure
C. Garcia Giron: Financial Interests, Institutional, Invited Speaker: BMS, Novartis, Ipsen. G. Crespo Herrero: Financial Interests, Institutional, Invited Speaker: BMS, Novartis, Ipsen, Jannsen, Sanofi, Evsa Pharma, Pierre Fabre, MSD, Eisai, Bayer. All other authors have declared no conflicts of interest.