Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

Nicola Veronese, Nicola Valeri, Cristiano Lanza, Matteo Fassan, Fotios Loupakis, Rocco Cappellesso, Nicola Veronese, Edoardo D'Angelo, Luca Vianello, Claudio Luchini, Giada Munari, Giuseppe N. Fanelli, Diana Sacchi, Marco Scarpa, Claudia Mescoli, Roberta Salmaso, Sara Lonardi, Salvatore Pucciarelli, Massimo Rugge, Marco Agostini

Risultato della ricerca: Articlepeer review

1 Citazioni (Scopus)

Abstract

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).
Lingua originaleEnglish
Numero di pagine3
RivistaCancer Cell International
Volume18
Stato di pubblicazionePublished - 2018

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

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