1189P - Mixed neuroendocrine-non neuroendocrine neoplasms (MiNEN): Characterization of the genomic and pathological profile

Background

Minens is a novel defined rare entity consisting of two morphologically distinct neoplastic components: one neuroendocrine (Nen) and the other nonneuroendocrine (nNen). Because limited data are available, the epidemiology and pathogenesis of Minens remain largely unknown. This study aims to shed light on the molecular and immunological basis of such a mixed neoplasm by investigating its individual components (Nen and nNen).

Methods

A total of 18 Minen patients with available archival tissue material (under treatment at the IRCCS "G.Pascale" of Naples from 2010 to date), will be examined by clinical review, IHC analysis and sequencing via the Illumina tso500 panel. Each primary NEN and nNEN component was obtained by laser microdissection (LMC).

Results

Preliminary data showed a similiar cumulative coverage in samples. Patients had a homogeneous percentage distribution related to Snps and, excluding synonymous mutations, we found an average of 700 variants of 194 genes. Notably, 45.42% of the mutations were shared in both the parts among all the patients, while unique mutations remained unique after intersection among groups. We have also investigated Vafs of shared and unique mutations between tumoral component. Different trend was observed among exclusive mutations in each patients although the load of mutation with low Vafs stayed the same. The latter might indicate that subclone mutations arises later in the tumor's expansion, whereas the presence of high Vafs in shared mutations suggests a possible simultaneous origin in the early stages. Both phenotypes might contribute to the insurgency of the tumor. To interpret the biological role of amplified genes we performed a GO term analysis, that indicated a common involvement for of the PI3K/AKT axis.

Conclusions

We suggest that Minens are mainly of monoclonal origin, but they may undergo bi-phenotypic differentiation during the carcinogenesis process. New drug development should exploit the common biological vulnerabilities between the two components. From our results, a potential molecular target could see the PI3K/AKT/mTor signaling pathway involved.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.