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Title: | Neuronal Distribution in Colorectal Cancer: Associations With Clinicopathological Parameters and Survival | Authors: | Massen, Maartje THIJSSEN, Meike Rademakers, Glenn Idris, Musa Wouters, Kim A. D. van der Meer, Jaleesa R. M. Buekers, Nikkie Huijgen, Desiree Samarska, Iryna, V Weijenberg, Matty P. van den Brandt, Piet A. van Engeland, Manon Gijbels, Marion J. BOESMANS, Werend Smits, Kim M. MELOTTE, Veerle |
Issue Date: | 2024 | Publisher: | ELSEVIER SCIENCE INC | Source: | Modern pathology, 37 (10) (Art N° 100565) | Abstract: | Over the past years, insights in the cancer neuroscience field increased rapidly, and a potential role for neurons in colorectal carcinogenesis has been recognized. However, knowledge on the neuronal distribution, subtypes, origin, and associations with clinicopathological characteristics in human studies is sparse. In this study, colorectal tumor tissues from the Netherlands Cohort Study on diet and cancer (n = 490) and an in-cohort validation population (n = 529) were immunohistochemically stained for the pan-neuronal markers neurofilament (NF) and protein gene product 9.5 (PGP9.5) to study the association between neuronal marker expression and clinicopathological characteristics. In addition, tumor and healthy colon tissues were stained for neuronal subtype markers, and their immunoreactivity in colorectal cancer (CRC) stroma was analyzed. NF-positive and PGP9.5-positive nerve fibers were found within the tumor stroma and mostly characterized by the neuronal subtype markers vasoactive intestinal peptide and neuronal nitric oxide synthase, suggesting that inhibitory neurons are the most prominent neuronal subtype in CRC. NF and PGP9.5 protein expression were not consistently associated with tumor stage, sublocation, differentiation grade, and median survival. NF immunoreactivity was associated with a worse CRC-specific survival in the study cohort (P = .025) independent of other prognostic factors (hazard ratio, 2.31; 95% CI, 1.33-4.03; P=.003), but these results were not observed in the in-cohort validation group. PGP9.5, in contrast, was associated with a worse CRC-specific survival in the in-cohort validation (P = .046) but not in the study population. This effect disappeared in multivariate analyses (hazard ratio, 0.81; 95% CI, 0.50-1.32; P=.393), indicating that this effect was dependent on other prognostic factors. This study demonstrates that the tumor stroma of CRC patients mainly harbors inhibitory neurons and that NF as a single marker is significantly associated with a poorer CRCspecific survival in the study cohort but necessitates future validation. (c) 2024 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). | Notes: | Melotte, V (corresponding author), Maastricht Univ, GROW Res Inst Oncol & Reprod, Dept Pathol, Med Ctr, Maastricht, Netherlands.; Melotte, V (corresponding author), Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. veerle.melotte@maastrichtuniversity.nl |
Keywords: | colorectal cancer;prognosis;(enteric) nervous system;neurofilament;protein gene product 9.5;neuronal subtypes | Document URI: | http://hdl.handle.net/1942/44260 | ISSN: | 0893-3952 | e-ISSN: | 1530-0285 | DOI: | 10.1016/j.modpat.2024.100565 | ISI #: | 001298313500001 | Rights: | 2024 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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Neuronal Distribution in Colorectal Cancer_ Associations With Clinicopathological Parameters and Survival.pdf | Published version | 2.33 MB | Adobe PDF | View/Open |
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