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. 2023 Jun;128(12):2218-2226.
doi: 10.1038/s41416-023-02258-2. Epub 2023 Apr 8.

Immunological and prognostic significance of tumour necrosis in colorectal cancer

Meeri Kastinen  1 , Päivi Sirniö  1 , Hanna Elomaa  2   3 , Maarit Ahtiainen  4 , Sara A Väyrynen  5 , Karl-Heinz Herzig  6   7 , Sanna Meriläinen  1 , Raila Aro  1 , Reetta Häivälä  1 , Tero Rautio  1 , Juha Saarnio  1 , Erkki-Ville Wirta  8   9 , Olli Helminen  1 , Toni T Seppälä  9   10   11 , Teijo Kuopio  2   4 , Jan Böhm  4 , Anne Tuomisto  1 , Jukka-Pekka Mecklin  3   12 , Markus J Mäkinen  1 , Juha P Väyrynen  13
Affiliations

Immunological and prognostic significance of tumour necrosis in colorectal cancer

Meeri Kastinen et al. Br J Cancer. 2023 Jun.

Abstract

Background: Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC.

Methods: Three independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined.

Results: Higher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68-6.17, Ptrend < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour.

Conclusions: Our results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis.

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Conflict of interest statement

TTS is the CEO and co-owner of Healthfund Finland Oy, and reports interview honoraria from Boehringer Ingelheim Finland and Amgen Finland.

Figures

Fig. 1
Fig. 1. Tumour necrosis in colorectal cancer.
a Large regions of coagulative necrosis in a haematoxylin & eosin-stained tumour resection specimen. b Several smaller pools of intraluminal necrosis in another resection sample. c Flowcharts of the patients and cohorts analyzed in the study. RT/CRT radiotherapy or chemoradiotherapy.
Fig. 2
Fig. 2. Kaplan–Meier survival analyses.
The associations of tumour necrosis with (a) cancer-specific survival (CSS) and (b) overall survival (OS) in Cohort 1. The associations of tumour necrosis with (c) CSS and (d) OS in Cohort 2.
See this image and copyright information in PMC

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