BACKGROUND: Tumours of appendix, including classic carcinoid tumour (CCT), goblet cell carcinoid (GCC), low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm/mucinous carcinoma (MCA) and non-mucinous adenocarcinoma (NMA), show different and sometimes mixed morphological features. It was hypothesised that these tumours originate from common tumour stem cell(s) with potential of various cell lineage differentiation. In normal intestinal epithelium, absorptive lineage (enterocytes) differentiation is driven by Notch-Hes1 pathway, while secretory lineage is driven by Wnt-Math1 pathway and further separated by different downstream signallings into three sublineages (Gfi1-Klf4/Elf3 for goblet cells, Gfi1-Sox9 for Paneth cells and Ngn3-Pdx1/Beta2/Pax4 for enteroendocrine cells). METHODS: The expressions of various signalling proteins in different appendiceal tumours were detected by immunohistochemistry on tumour tissue microarray. RESULTS: CCT showed reduced Hes1/Elf3 and Sox9/Klf4 coupled with elevated Math1, in keeping with endocrine phenotype. As compared with CCT, GCC showed higher Klf4 and similar Ngn3/Pax4, indicative of a shift of differentiation towards goblet cells as well as endocrine cells. GCC displayed a Notch signalling similar to adenocarcinoma. Mucinous tumours showed lower Elf3 than normal appendiceal epithelium and higher Math1/Gfi1/Klf4, suggestive of a differentiation towards less enterocytes but more goblet cells. NMA showed Notch signalling similar to other glandular tumours, but lower Klf4. However, some seemingly paradoxical changes were also observed, probably suggesting gene mutations and/or our incomplete understanding of the intestinal cell differentiation. CONCLUSIONS: Wnt/secretory lineage protein and Notch/absorptive lineage protein expression profiles are generally associated with the tumour cell differentiation and morphological diversity of common appendiceal tumours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
BACKGROUND:Tumours of appendix, including classic carcinoid tumour (CCT), goblet cell carcinoid (GCC), low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm/mucinous carcinoma (MCA) and non-mucinous adenocarcinoma (NMA), show different and sometimes mixed morphological features. It was hypothesised that these tumours originate from common tumour stem cell(s) with potential of various cell lineage differentiation. In normal intestinal epithelium, absorptive lineage (enterocytes) differentiation is driven by Notch-Hes1 pathway, while secretory lineage is driven by Wnt-Math1 pathway and further separated by different downstream signallings into three sublineages (Gfi1-Klf4/Elf3 for goblet cells, Gfi1-Sox9 for Paneth cells and Ngn3-Pdx1/Beta2/Pax4 for enteroendocrine cells). METHODS: The expressions of various signalling proteins in different appendiceal tumours were detected by immunohistochemistry on tumour tissue microarray. RESULTS: CCT showed reduced Hes1/Elf3 and Sox9/Klf4 coupled with elevated Math1, in keeping with endocrine phenotype. As compared with CCT, GCC showed higher Klf4 and similar Ngn3/Pax4, indicative of a shift of differentiation towards goblet cells as well as endocrine cells. GCC displayed a Notch signalling similar to adenocarcinoma. Mucinous tumours showed lower Elf3 than normal appendiceal epithelium and higher Math1/Gfi1/Klf4, suggestive of a differentiation towards less enterocytes but more goblet cells. NMA showed Notch signalling similar to other glandular tumours, but lower Klf4. However, some seemingly paradoxical changes were also observed, probably suggesting gene mutations and/or our incomplete understanding of the intestinal cell differentiation. CONCLUSIONS: Wnt/secretory lineage protein and Notch/absorptive lineage protein expression profiles are generally associated with the tumour cell differentiation and morphological diversity of common appendiceal tumours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Nicola S Meagher; Linyuan Wang; Peter F Rambau; Maria P Intermaggio; David G Huntsman; Lynne R Wilkens; Mona A El-Bahrawy; Roberta B Ness; Kunle Odunsi; Helen Steed; Esther Herpel; Michael S Anglesio; Bonnie Zhang; Neil Lambie; Anthony J Swerdlow; Jan Lubiński; Robert A Vierkant; Ellen L Goode; Usha Menon; Aleksandra Toloczko-Grabarek; Oleg Oszurek; Sanela Bilic; Aline Talhouk; Montserrat García-Closas; Qin Wang; Adeline Tan; Rhonda Farrell; Catherine J Kennedy; Mercedes Jimenez-Linan; Karin Sundfeldt; John L Etter; Janusz Menkiszak; Marc T Goodman; Paul Klonowski; Yee Leung; Stacey J Winham; Kirsten B Moysich; Sabine Behrens; Tomasz Kluz; Robert P Edwards; Jacek Gronwald; Francesmary Modugno; Brenda Y Hernandez; Christine Chow; Linda E Kelemen; Gary L Keeney; Michael E Carney; Yanina Natanzon; Gregory Robertson; Raghwa Sharma; Simon A Gayther; Jennifer Alsop; Hugh Luk; Chloe Karpinskyj; Ian Campbell; Peter Sinn; Aleksandra Gentry-Maharaj; Penny Coulson; Jenny Chang-Claude; Mitul Shah; Martin Widschwendter; Katrina Tang; Minouk J Schoemaker; Jennifer M Koziak; Linda S Cook; James D Brenton; Frances Daley; Björg Kristjansdottir; Constantina Mateoiu; Melissa C Larson; Paul R Harnett; Audrey Jung; Anna deFazio; Kylie L Gorringe; Paul D P Pharoah; Parham Minoo; Colin Stewart; Oliver F Bathe; Xianyong Gui; Paul Cohen; Susan J Ramus; Martin Köbel Journal: Mod Pathol Date: 2019-06-25 Impact factor: 8.209
Authors: Kieran Palmer; Scott Weerasuriya; Kandiah Chandrakumaran; Brian Rous; Benjamin E White; Sangeeta Paisey; Rajaventhan Srirajaskanthan; John K Ramage Journal: Front Oncol Date: 2022-07-12 Impact factor: 5.738