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Background/Aim: P21 is a cyclin-dependent kinase inhibitor regulating the cell cycle as a tumor suppressor. Using a p21 immunohistochemistry (IHC) assay, we compared tumor p21 levels with conventional clinico-pathological criteria in primary pancreatic endocrine tumor subsets with and without liver metastases. Materials and Methods: Sections from tissue microarray (TMA) including 13 archival metastatic primary and 18 non-metastatic primary pancreatic endocrine carcinomas/tumors (MP-PECAs/NMP-PETs) were stained with a monoclonal anti-p21WAFI,CIP primary antibody. Tumor p21 IHCs were scored as the sum of intensity (0-3) and proportion scores (0-5) (Total Allred score: 0-8), and as p21% labelling index in the tumor. ROC curve analysis was used for most optimal p21 score cut-off (4 or >) and Fisher's exact test was used to compare the association among tumor p21 scores, conventional prognostic criteria, and liver metastases. Results: For PET/PECA patients, mean ages were 55.6 years (27-73) and 49.3 years (28-71), M/F ratios were 7/11 and 7/6. Mean p21 labelling index (%) for MP-PECAs was 24% (range=3-63%) vs. 9% for NMP-PETs (range=1-25%) (p=0.022). The mean p21 index in MP-PECAs was significantly higher (24%) as compared to PIs (7%) (p=0.0047). Using a p21 Allred score of ≥4, high p21 IHC score had strong association with the presence of liver metastases (p-value <0.001). High tumor p21 IHC score had a 93% sensitivity, 68% specificity, 78% predictive accuracy, 66% positive, and 94% negative predictive values. Conclusion: In patients with primary PETs, p21 IHC is superior to conventional criteria in predicting presence or absence of liver metastases. [ABSTRACT FROM AUTHOR]

Background/Aim: Cancers with a microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status respond to immune checkpoint inhibition (ICI). Regardless of the tumor type, MSI-H/dMMR status is a reliable biomarker for ICI responsiveness. This study aimed at determining the MSI-H status in precursor lesions to esophageal adenocarcinoma (EAC) such as Barrett’s esophagus (BE) and BE with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). Patients and Methods: We performed immunohistochemical staining (IHC) for PMS2, MSH6, PD1, and PD-L1. Results: All cases of BE (50), LGD (48), and HGD (50) had intact PMS2 and MSH6 nuclear expression; were negative for PD1; and had a PD-L1 combined positive score (CPS) score <1. One EAC case (2%) was negative for PMS2 nuclear expression. One HGD case (2%) and two EAC cases (4%) were PD1 positive (CPS score <1 applied to PD1). One EAC case (2%) had a CPS score >1, and one EAC case (2%) was MSI-H. MSI-H tumors usually show PD-L1 expression, although the MSI-H EAC in this study had a PD-L1 CPS score of <1. Conclusion: Further studies investigating EAC and its precursor lesions for PD1, PD-L1, and dMMR status may be informative regarding the immunogenicity of the evolution of EAC. [ABSTRACT FROM AUTHOR]

Background/aim: Cancer of unknown primary (CUP), representing 3-5% of all newly diagnosed cancers in the United States, is a presumptive, non-definitive diagnosis rendered when a primary tumor site cannot be identified after exhaustive diagnostic evaluation, including cases of neuroendocrine neoplasms (NENs). CUPs are characterized by findings that are challenging to reconcile, including inconclusive immunohistochemical (IHC) stains, an undifferentiated morphologic phenotype, history of multiple cancers, a clinical presentation that is discordant from histologic findings, an atypical distribution of metastases, or lack of expected response to treatment. For a significant subset of NENs (10%), traditional diagnostic evaluation is unable to determine a primary tumor site using histomorphology and IHC stains. Gene expression profiling (GEP) of either mRNA or microRNA is the technique utilized in the three commercially available platforms that provide a prediction of tumor type in cases of diagnostic uncertainty of CUPs, including those with neuroendocrine differentiation. Case Series Report: Here we present four cases of NENs, where the diagnosis based upon histomorphological and IHC features presented a unique challenge that ultimately benefited from the integration of molecular tumor classification using the validated assay. CancerTYPE ID by Biotheranostics is based on a quantitative RT-PCR assay that uses a computational algorithm to measure the collective expression of 92 genes (87 cancer-related genes and 5 control genes). This case series reports five appropriate clinical scenarios that highlight the utility of a GEP-based assay to effectively provide a molecular tumor classification to identify NEN subtypes and tumor primary site of origin., Conclusion: These cases demonstrated that the CancerTYPE ID test was able to resolve challenging diagnoses for primary and metastatic NENs. These cases emphasize the clinical need of utilizing a GEP-based assay for determining the anatomic site of origin and NEN subtyping, both essential for the appropriate clinical management of NENs., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)