Immunohistochemistry features and molecular pathology of appendiceal neoplasms
Creators: name: Mikaeel, Reger R.
name: Young, Joanne P.
name: Rico, Gonzalo Tapia
name: Hewett, Peter J.
name: Hardingham, Jennifer E.
name: Uylaki, Wendy
name: Horsnell, Mehgan
name: Price, Timothy J.
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer

description: Primary appendiceal neoplasms (ANs) comprise a heterogeneous group of tumors. The pathology and classification of ANs have been controversial, and thus, a new classification of these neoplasms was published in the World Health Organization (WHO) classification of tumors (5th edition, 2019). However, immunohistochemistry (IHC) features of epithelial ANs are not explained in this edition and the limited data on the molecular pathology of these tumors shows inconsistent findings in various studies. It would be useful to identify biomarkers appropriate for each subtype to better aid in treatment selection. Therefore, we reviewed the literature to investigate what is known of the molecular pathology and IHC features of the most frequently diagnosed pathological subtypes of epithelial ANs based on the recent classification. The inconsistencies in research findings regarding the IHC features and molecular pathology of ANs could be due to differences in the number of samples and their collection and preparation as well as to the lack of a universally accepted classification system for these neoplasms. However, the literature shows that epithelial ANs typically stain positive for MUC2, CK20, and CDX2 and that the expression of SATB2 protein could be used as a biomarker for appendix tumor origin. Low-grade appendiceal mucinous neoplasms tend to have mutations in <i>KRAS</i> and <i>GNAS</i> but are usually wild-type for <i>BRAF</i>, <i>APC</i>, and <i>P53</i>. Conversely, appendiceal adenocarcinomas are frequently found with mutations in <i>KRAS</i>, <i>GNAS</i>, <i>P53</i>, <i>PIK3CA</i>, and <i>APC</i>, and have significant nuclear expression of β-catenin, loss of nuclear or nuclear and cytoplasmic expression of SMAD4, and loss of cytoplasmic membranous expression of E-cadherin. Goblet cell carcinomas (GCCs) typically stain positive for keratin and mucin markers and are frequently mutated in <i>P53</i> and chromatin-modifier genes, but they tend to be wild-type for <i>KRAS</i>, <i>GNAS</i>, <i>APC</i>, and <i>PIK3CA.</i> The expression of CK7 and SATB2 proteins is usually negative in appendiceal neuroendocrine neoplasms and they lack the mutations in common cancer-associated genes including <i>APC</i>, <i>BRAF</i>, <i>SMAD4</i>, and <i>PIK3C.</i> The available data suggest that GCCs have distinct molecular and immunohistochemical features and that they have characteristics more in common with adenocarcinoma than classical neuroendocrine tumors. In addition, MSI does not seem to have a role in the pathogenesis of epithelial ANs because they are rarely detected in these tumors. Finally, hereditary predisposition may have a role in the development of ANs because heterozygous <i>CTNNβ1</i>, <i>NOTCH1,</i> and <i>NOTCH4</i> germline mutations have recently been identified in low and high grades ANs.