Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases.
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Date
2018-09-06ICR Author
Author
Fassan, M
Vianello, L
Sacchi, D
Fanelli, GN
Munari, G
Scarpa, M
Cappellesso, R
Loupakis, F
Lanza, C
Salmaso, R
Mescoli, C
Valeri, N
Agostini, M
D'Angelo, E
Lonardi, S
Pucciarelli, S
Veronese, N
Luchini, C
Rugge, M
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: No data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC). METHODS: A series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n = 66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53 genes. RESULTS: A significantly higher percentage of CD4-, CD8- and CD68-positive cells was observed at the invasive front of both CRCs and in ENE in contrast with what observed at the core of both CRCs and their matched nodal metastases. ENE was also characterized by a significantly higher number of CD80-positive cells. No significant difference was observed in PD-L1 distribution among the different specimens. Fourteen out of 15 CRCs (93%) showed at least a driver mutation. The most frequently mutated gene was TP53 (n = 8 tumors), followed by APC (n = 6), BRAF (n = 4), KRAS, NRAS and PIK3CA (n = 2). In 11 out of 15 CRCs (73%) the mutational profiling of the primary tumor was consistent with what obtained from the two matched LNs. CONCLUSIONS: A heterogeneous intratumor immune-microenvironment has been observed in ENE-positive CRCs, which are characterized by an increased leukocytic infiltration at the ENE invasive front.
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Research team
Gastrointestinal Cancer Biology and Genomics
Language
eng
Date accepted
2018-09-03
License start date
2018-01
Citation
Cancer cell international, 2018, 18 pp. 131 - ?
Publisher
BMC