Large-Section Histopathology Can Better Indicate the Immune Microenvironment and Predict the Prognosis of Pancreatic Ductal Adenocarcinoma Than Small-Section Histopathology

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor and is insensitive to radiotherapy and chemotherapy, as it is highly correlated with its complex tumor microenvironment (TME). A comprehensive description of PDAC’s immune microenvironment at the pathological level has not been reported, thus limiting its treatment. Previous studies have shown that large-section histopathology (LSH) can reveal the complete structure and margin of the tumor on a single slice and effectively reflect intratumoral heterogeneity. LSH, as opposed to classic small-section histopathology (SSH), can also be used to explore the infiltration state of immune cells in different regions. In the current study, EnVision immunohistochemical staining was used to explore the panoramic distribution of CD4-, CD8-, CD15-, CD20-, and CD56 (surface markers of helper T cells, cytotoxic T cells, neutrophils, B cells, and NK cells, respectively)-positive cells in 102 pairs of paraffin wax-embedded PDAC samples (LSH vs SSH) for the first time. These indicators were then analyzed, and correlations of clinicopathological characteristics with clinical prognoses were analyzed. The findings of this study show that LSH can effectively indicate more immune cells than SSH. Upregulated CD4, CD8, CD20, and CD56 or downregulated CD15 was correlated with a good prognosis in PDAC patients. However, analysis of SSH showed that only upregulated CD4 and CD8 can be used as indicators of a good prognosis. Multivariate Cox regression analysis showed that 7 variables, namely, pTNM stage (P=0.002), PDL1 expression (P=0.001), CDX2 expression (P=0.008), DPC4 expression (P=0.004), CD4 expression in LSH (P<0.001), CD8 expression in LSH (P=0.010) and CD15 expression in LSH (P=0.031), were significantly correlated with the prognosis of PDAC patients. The findings of this study indicate that LSH is an effective tool for a panoramic assessment of the immune microenvironment in pancreatic cancer patients.

Characterization of natural killer and cytotoxic T‐cell immune infiltrates in pancreatic ductal adenocarcinoma

“…32 Additionally, the use of NKp46 in our study as a marker for NK cells may contribute to discrepancies with previous studies, most of which show NK cell infiltration to be associated with improved survival using CD56 as the NK marker. 33 Although CD56 is a reliable NK cell marker by flow cytometry, by single color IHC, it can be nonspecific and stain neural cells and other lymphoid cell types. On the other hand, although…”

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy: a narrative review

“…Fifth, significant interobserver variation still persists, especially for HCC with multiple nodules, dispersive growing pattern, cystic degeneration, and massive fibrosis, despite best efforts to minimize subjectivity. Combined with large-section histopathology ( 83 ) and artificial intelligence pathology ( 84 , 85 ) is a promising means to solve this issue in the future.…”