TY - JOUR
T1 - Tertiary lymphoid structures in pulmonary metastases of microsatellite stable colorectal cancer
AU - Karjula, Topias
AU - Niskakangas, Anne
AU - Mustonen, Olli
AU - Puro, Iiris
AU - Elomaa, Hanna
AU - Ahtiainen, Maarit
AU - Kuopio, Teijo
AU - Mecklin, Jukka Pekka
AU - Seppälä, Toni T.
AU - Wirta, Erkki Ville
AU - Sihvo, Eero
AU - Yannopoulos, Fredrik
AU - Helminen, Olli
AU - Väyrynen, Juha P.
N1 - Funding Information:
Open Access funding provided by University of Oulu including Oulu University Hospital. This study was funded by Instrumentarium Science Foundation (OH), Mary and Georg C. Ehrnrooth Foundation (OH) and Finnish State Research Funding (OH, J-P.M), Cancer Foundation Finland (J.P.V), J&A Erkko Foundation (J-P.M, TTS).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates located at sites of chronic inflammation and recognized as prognosticators in several cancers. We aimed to analyse the prognostic effect of TLSs in colorectal cancer (CRC) pulmonary metastases and primary tumours, with a comparison to the CD3+ and CD8+ cell density-based immune cell score (ICS). For TLS density and TLS maximum diameter analysis, 67 pulmonary metastases and 63 primary tumours were stained with haematoxylin and eosin. For ICS scoring and analysis, CD3 and CD8 immunohistochemistry was performed. Excellent interobserver agreement was achieved in all TLS measurements. Of all patients, 36 patients had low TLS density (< 0.222 follicles/mm) and 31 patients had high TLS density (≥ 0.222 follicles/mm) in the first resected pulmonary metastases. TLS density (adjusted HR 0.91, 0.48–1.73) or maximum diameter (adjusted HR 0.78, 0.40–1.51) did not have prognostic value in pulmonary metastases. In primary tumours, higher TLS density (adjusted HR 0.39, 0.18–0.87) and maximum diameter (adjusted HR 0.28, 0.11–0.73) were associated with lower mortality. In the pulmonary metastases, ICS had superior prognostic value to TLSs; however, TLSs and ICS were significantly associated. In conclusion, TLSs in CRC pulmonary metastases had no prognostic value but correlated with the ICS. TLSs in primary tumours associated with favourable prognosis.
AB - Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates located at sites of chronic inflammation and recognized as prognosticators in several cancers. We aimed to analyse the prognostic effect of TLSs in colorectal cancer (CRC) pulmonary metastases and primary tumours, with a comparison to the CD3+ and CD8+ cell density-based immune cell score (ICS). For TLS density and TLS maximum diameter analysis, 67 pulmonary metastases and 63 primary tumours were stained with haematoxylin and eosin. For ICS scoring and analysis, CD3 and CD8 immunohistochemistry was performed. Excellent interobserver agreement was achieved in all TLS measurements. Of all patients, 36 patients had low TLS density (< 0.222 follicles/mm) and 31 patients had high TLS density (≥ 0.222 follicles/mm) in the first resected pulmonary metastases. TLS density (adjusted HR 0.91, 0.48–1.73) or maximum diameter (adjusted HR 0.78, 0.40–1.51) did not have prognostic value in pulmonary metastases. In primary tumours, higher TLS density (adjusted HR 0.39, 0.18–0.87) and maximum diameter (adjusted HR 0.28, 0.11–0.73) were associated with lower mortality. In the pulmonary metastases, ICS had superior prognostic value to TLSs; however, TLSs and ICS were significantly associated. In conclusion, TLSs in CRC pulmonary metastases had no prognostic value but correlated with the ICS. TLSs in primary tumours associated with favourable prognosis.
KW - Microsatellite stable colorectal cancer
KW - Pulmonary metastasis
KW - Tertiary lymphoid structures
U2 - 10.1007/s00428-023-03577-8
DO - 10.1007/s00428-023-03577-8
M3 - Article
C2 - 37337034
AN - SCOPUS:85161962758
SN - 0945-6317
VL - 483
SP - 21
EP - 32
JO - VIRCHOWS ARCHIV
JF - VIRCHOWS ARCHIV
IS - 1
ER -
