TY - JOUR
T1 - Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases
AU - Veronese, Nicola
AU - Valeri, Nicola
AU - Lanza, Cristiano
AU - Fassan, Matteo
AU - Loupakis, Fotios
AU - Cappellesso, Rocco
AU - Veronese, Nicola
AU - D'Angelo, Edoardo
AU - Vianello, Luca
AU - Luchini, Claudio
AU - Munari, Giada
AU - Fanelli, Giuseppe N.
AU - Sacchi, Diana
AU - Scarpa, Marco
AU - Scarpa, Marco
AU - Scarpa, Marco
AU - Mescoli, Claudia
AU - Salmaso, Roberta
AU - Lonardi, Sara
AU - Pucciarelli, Salvatore
AU - Rugge, Massimo
AU - Agostini, Marco
PY - 2018
Y1 - 2018
N2 - 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. © 2018 The Author(s).
AB - 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. © 2018 The Author(s).
UR - http://hdl.handle.net/10447/455335
UR - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052932646&doi=10.1186/s12935-018-0634-8&partnerID=40&md5=b77dd9533d6ab744312a500a47b63bbc
M3 - Article
VL - 18
JO - Cancer Cell International
JF - Cancer Cell International
SN - 1475-2867
ER -