An miRNA Signature Predicts Grading of Pancreatic Neuroendocrine Neoplasms.

BACKGROUND/AIM: Grading pancreatic neuroendocrine neoplasms (PNENs) via mitotic rate and Ki-67 index score is complicated by interobserver variability. Differentially expressed miRNAs (DEMs) are useful for predicting tumour progression and may be useful for grading. PATIENTS AND METHODS: Twelve PNENs were selected. Four patients had grade (G) 1 pancreatic neuroendocrine tumours (PNETs); 4 had G2 PNETs; and 4 had G3 PNENs (2 PNETs and 2 pancreatic neuroendocrine carcinomas). Samples were profiled using the miRNA NanoString Assay. RESULTS: There were 6 statistically significant DEMs between different grades of PNENs. MiR1285-5p was the sole miRNA differentially expressed (p=0.03) between G1 and G2 PNETs. Six statistically significant DEMs (miR135a-5p, miR200a-3p, miR3151-5p, miR-345-5p, miR548d-5p and miR9-5p) (p<0.05) were identified between G1 PNETs and G3 PNENs. Finally, 5 DEMs (miR155-5p, miR15b-5p, miR222-3p, miR548d-5p and miR9-5p) (p<0.05) were identified between G2 PNETs and G3 PNENs. CONCLUSION: The identified miRNA candidates are concordant with their patterns of dysregulation in other tumour types. The reliability of these DEMs as discriminators of PNEN grades support further investigations using larger patient populations.

Unusual Microsatellite-Instable Mixed Neuroendocrine and Non-neuroendocrine Neoplasm: A Clinicopathological Inspection and Literature Review.

BACKGROUND: Mixed neuroendocrine and non-endocrine neoplasms (MiNENs) are challenging to diagnose and manage clinically. The current understanding of MiNENs' pathobiology, molecular mechanisms, and management is incomplete. Though microsatellite instability (MSI) is known to impact carcinogenesis, reports examining MSI mechanisms for MiNENs are rare. METHODS: We report an unusual colonic MSI-MiNEN uncovered in an 89-year-old woman and the review of the literature. RESULTS: Pathologic inspection revealed a high-grade carcinoma composed of tumor cells with neuroendocrine histologic traits and immunophenotype intermixed with mucin-containing signet ring-like cells arranged in nested and micronodular patterns. Loss of MLH1 and PMS2 mismatch repair proteins was detected in tumor cells. INSM1 immunostaining highlighted about 50% of the tumour, further reinforcing the MiNEN diagnosis. Next-generation sequencing identified multiple carcinogenic mutations. Because of the advanced stage of the tumor and its adhesion to the adjacent organs, surgical resection was aborted; immunotherapy was initiated. The tumor is in remission 30 months following initiation of treatment, and the patient remains asymptomatic. CONCLUSION: This unique MSI MiNEN was characterized by its immunohistochemical and molecular signatures and illustrated how correctly diagnosing MSI can strongly improve a patient's outcomes.