The Increase of miR-195-5p Reduces Intestinal Permeability in Ulcerative Colitis, Modulating Tight Junctions' Expression.

Defects in the intestinal epithelial barrier functions characterize inflammatory conditions such as Inflammatory Bowel Disease (IBD). Overexpression of pro-inflammatory cytokines such as TNF-α, IL-1B, IL-6 and INF-γ trigger epithelial damage. These cytokines are due to upregulation of claudin-2 (CLDN2) that form a pore channel, resulting in redistribution of TJs and an alteration of barrier permeability. Recently, we demonstrated that miR-195-5p is able to regulate CLDN2 and indirectly also CLDN1 in intestinal epithelial cells. Now, we aimed to investigate the modulation of miR-195-5p on the expression of CLDN2 and other TJs under inflammatory conditions induced by TNF-α. We demonstrated that miR-195-5p also modulated the expression of CLDN2 levels after stimulation with TNF-α. In addition, we discovered the role of miR-195-5p in the integrity of the intestinal barrier and in promoting the restoration of the intestinal epithelial. Moreover, we established that replacement of miR-195-5p attenuated the colonic inflammatory response in DSS-induced, colitis and it reduced colonic permeability. In conclusion, our data revealed the role of miR-195-5p in intestinal inflammation in ulcerative colitis, suggesting a potential pharmacological target for new therapeutic approaches.

Role of Immunohistochemistry in Suspected Pancreatic Ductal Adenocarcinoma: A Prospective Study on Fine Needle Aspiration Biopsies.

OBJECTIVES: Differential diagnosis between pancreatic ductal adenocarcinoma (PDAC) and benign mimickers can be very difficult on small histological samples, such as fine needle aspiration biopsies (FNAB). We aimed to investigate the diagnostic value of immunostaining for IMP3, Maspin, S100A4, S100P, TFF2, and TFF3 in FNAB pancreatic lesions. METHODS: We prospectively enrolled 20 consecutive patients with suspected PDAC, collecting FNABs at our department between 2019 and 2021. RESULTS: Three of the 20 enrolled patients resulted negative for all immunohistochemical markers, while all the others were positive for Maspin. All other immunohistochemistry (IHC) markers had sensitivity and accuracy of less than 100%. On the basis of the IHC, the preoperative diagnosis on FNAB was nonmalignant lesions in the IHC negative cases and PDAC in the others. All patients subsequently underwent surgery for the pancreatic solid mass demonstrated by imaging techniques. The concordance between the preoperative and postoperative diagnosis was 100%; all IHC negative samples were diagnosed on surgical specimens as chronic pancreatitis and Maspin-positive samples as PDAC. CONCLUSIONS: Our results demonstrate that even in the presence of little histological material, such as FNAB, the use of Maspin alone is sufficient to discriminate between PDAC and nonmalignant pancreatic lesions, with 100% accuracy.

Assessment and management of undifferentiated carcinoma with osteoclastic like giant cells of the pancreas: a case report and revision of literature.

BACKGROUND: Undifferentiated carcinoma with osteoclast-like giant cells (UCOGCs) is a rare and aggressive non endocrine pancreatic carcinoma characterized by the presence of osteoclastic giant cells mixed with mononuclear cell. Very few cases have been reported in the literature and the histogenesis is controversial as, at the time of diagnosis, the tumor is often of advanced size and stage and it is difficult to pathologically observe its relationship with the pancreatic duct. CASE PRESENTATION: We present a case of 65-year-old male patient presenting with abdominal pain, nausea, and weight loss, which was treated with surgical resection. Histological examination revealed an undifferentiated pancreatic carcinoma with osteoclast-like giant cells. The patient underwent to a routine pylorus preserving pancreatoduodenectomy. Actually, the patient was in good performance status and disease-free five months. CONCLUSIONS: Based on the present case and limited previous data, further researches preferably with large cohorts are necessary to clarify the pathogenesis of the neoplasm. However, as show in this case, histopathological and immunohistochemically studies are the gold standard for the diagnosis of UCPOGC. Investigation of the genomic alterations in UPOGCs could help to explain the histologic diversity of variant tumor and could provide a genetic basis for prognosis and treatment.

Are Immunohistochemical Markers Useful in Phenotypic Gastric Cancer Classification?

To identify useful markers for prognostic and therapeutic purposes, The Cancer Genome Atlas (TCGA) provided a molecular classification of gastric cancers (GCs). Previous studies have used immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) to define immunophenotypic surrogate markers of the molecular alterations. Some critical issues concerning the correct definition of immunophenotypic groups have emerged in these studies that employed tissue microarrays (TMAs). We performed an immunophenotypic classification by evaluating MLH1, p53, HER2, E-cadherin, and Epstein-Barr virus (EBV) on the whole section of the surgical GC samples compared to most of the studies conducted on TMAs. We also investigated the immunohistochemical expression of PD-L1, a known therapeutic target. We identified the following immunophenotypic groups: EBV (2.9%); mismatch repair deficient (MMR-D) (7.2%); overexpressed p53 and/or HER2+ (61.4%); aberrant E-cadherin (11.4%); and normal pattern (17.1%). The use of surgical samples emphasized that some immunohistochemical markers were not useful for properly classifying the GC specimens. We can state that EBV (significantly correlated to PD-L1 expression) and MMR-D GCs are well-defined groups, mutually exclusive, and easily assessable with IHC and CISH, and could be candidates for immunotherapy with PD-1/PD-L1 inhibitors. As regards p53, our findings suggest that IHC assessment may be responsible for a misclassification of GC groups. Immunohistochemical evaluation of E-cadherin needs to be standardized, particularly in terms of the heterogeneous cytoplasmic/membranous staining pattern. Whether to consider the normal-pattern group as a separate category remains to be clarified. Because GC specimens with known therapeutic targets account for only 40%, we suggest reviewing the immunophenotypic classification to find new therapeutic targets, such as PD-L1, MLH1, and HER2.