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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number131
JournalCancer Cell International
Volume18
Issue number1
DOIs
Publication statusPublished - Sep 6 2018

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Colorectal Neoplasms
p53 Genes
Neoplasm Metastasis
Lymph Nodes
Neoplasms
Immunohistochemistry
Mutation

Keywords

  • Biomarkers
  • Colorectal cancer
  • Extranodal extension
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases. / Fassan, Matteo; Vianello, Luca; Sacchi, Diana; Fanelli, Giuseppe N.; Munari, Giada; Scarpa, Marco; Cappellesso, Rocco; Loupakis, Fotios; Lanza, Cristiano; Salmaso, Roberta; Mescoli, Claudia; Valeri, Nicola; Agostini, Marco; D'Angelo, Edoardo; Lonardi, Sara; Pucciarelli, Salvatore; Veronese, Nicola; Luchini, Claudio; Rugge, Massimo.

In: Cancer Cell International, Vol. 18, No. 1, 131, 06.09.2018.

Research output: Contribution to journalArticle

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 2018, 'Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases', Cancer Cell International, vol. 18, no. 1, 131. https://doi.org/10.1186/s12935-018-0634-8
Fassan, Matteo ; Vianello, Luca ; Sacchi, Diana ; Fanelli, Giuseppe N. ; Munari, Giada ; Scarpa, Marco ; Cappellesso, Rocco ; Loupakis, Fotios ; Lanza, Cristiano ; Salmaso, Roberta ; Mescoli, Claudia ; Valeri, Nicola ; Agostini, Marco ; D'Angelo, Edoardo ; Lonardi, Sara ; Pucciarelli, Salvatore ; Veronese, Nicola ; Luchini, Claudio ; Rugge, Massimo. / Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases. In: Cancer Cell International. 2018 ; Vol. 18, No. 1.
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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.",
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AU - Fassan, Matteo

AU - Vianello, Luca

AU - Sacchi, Diana

AU - Fanelli, Giuseppe N.

AU - Munari, Giada

AU - Scarpa, Marco

AU - Cappellesso, Rocco

AU - Loupakis, Fotios

AU - Lanza, Cristiano

AU - Salmaso, Roberta

AU - Mescoli, Claudia

AU - Valeri, Nicola

AU - Agostini, Marco

AU - D'Angelo, Edoardo

AU - Lonardi, Sara

AU - Pucciarelli, Salvatore

AU - Veronese, Nicola

AU - Luchini, Claudio

AU - Rugge, Massimo

PY - 2018/9/6

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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.

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.

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