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Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy

BACKGROUND: In patients receiving preoperative chemotherapy, colorectal liver metastases (CLM) are expected to demonstrate a similar behaviour because of similar organ microenvironment and tumour cell chemosensitivity. We focused on the occurrence of pathological and genetic heterogeneity within CLM...

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Autores principales: Sebagh, Mylène, Allard, Marc-Antoine, Bosselut, Nelly, Dao, Myriam, Vibert, Eric, Lewin, Maïté, Lemoine, Antoinette, Cherqui, Daniel, Adam, René, Cunha, Antonio Sa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008308/
https://www.ncbi.nlm.nih.gov/pubmed/26943031
http://dx.doi.org/10.18632/oncotarget.7809
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author Sebagh, Mylène
Allard, Marc-Antoine
Bosselut, Nelly
Dao, Myriam
Vibert, Eric
Lewin, Maïté
Lemoine, Antoinette
Cherqui, Daniel
Adam, René
Cunha, Antonio Sa
author_facet Sebagh, Mylène
Allard, Marc-Antoine
Bosselut, Nelly
Dao, Myriam
Vibert, Eric
Lewin, Maïté
Lemoine, Antoinette
Cherqui, Daniel
Adam, René
Cunha, Antonio Sa
author_sort Sebagh, Mylène
collection PubMed
description BACKGROUND: In patients receiving preoperative chemotherapy, colorectal liver metastases (CLM) are expected to demonstrate a similar behaviour because of similar organ microenvironment and tumour cell chemosensitivity. We focused on the occurrence of pathological and genetic heterogeneity within CLM. METHODS: Patients resected for multiple CLM between 2004 and 2011 after > three cycles of chemotherapy were included. Pathological heterogeneity was arbitrarily defined as a > 50% difference in the percentage of remaining tumour cells between individual CLM. In patients with pathological heterogeneity, the mutational genotyping (KRAS, NRAS, BRAF and PIK3CA) was determined from the most heterogeneous CLM. RESULTS: Pathological heterogeneity was observed in 31 of 157 patients with multiple CLM (median = 4, range, 2–32) (19.7%). In 72.4% of them, we found a concordance of the mutation status between the paired CLM: both wild-type in 55%, and both mutated in 17.2%. We observed a discordance of the mutation status of 27.6% between CLM: one mutated and the other wild-type. The mutated CLM was the less florid one in 75% of patients with genetic heterogeneity. CONCLUSIONS: Pathological heterogeneity is present in 19.7% of patients with multiple CLM. Genetic heterogeneity is present in 27.6% of patients with pathological heterogeneity. Heterogeneity could refine guide management for tissue sampling.
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spelling pubmed-50083082016-09-12 Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy Sebagh, Mylène Allard, Marc-Antoine Bosselut, Nelly Dao, Myriam Vibert, Eric Lewin, Maïté Lemoine, Antoinette Cherqui, Daniel Adam, René Cunha, Antonio Sa Oncotarget Research Paper BACKGROUND: In patients receiving preoperative chemotherapy, colorectal liver metastases (CLM) are expected to demonstrate a similar behaviour because of similar organ microenvironment and tumour cell chemosensitivity. We focused on the occurrence of pathological and genetic heterogeneity within CLM. METHODS: Patients resected for multiple CLM between 2004 and 2011 after > three cycles of chemotherapy were included. Pathological heterogeneity was arbitrarily defined as a > 50% difference in the percentage of remaining tumour cells between individual CLM. In patients with pathological heterogeneity, the mutational genotyping (KRAS, NRAS, BRAF and PIK3CA) was determined from the most heterogeneous CLM. RESULTS: Pathological heterogeneity was observed in 31 of 157 patients with multiple CLM (median = 4, range, 2–32) (19.7%). In 72.4% of them, we found a concordance of the mutation status between the paired CLM: both wild-type in 55%, and both mutated in 17.2%. We observed a discordance of the mutation status of 27.6% between CLM: one mutated and the other wild-type. The mutated CLM was the less florid one in 75% of patients with genetic heterogeneity. CONCLUSIONS: Pathological heterogeneity is present in 19.7% of patients with multiple CLM. Genetic heterogeneity is present in 27.6% of patients with pathological heterogeneity. Heterogeneity could refine guide management for tissue sampling. Impact Journals LLC 2016-03-01 /pmc/articles/PMC5008308/ /pubmed/26943031 http://dx.doi.org/10.18632/oncotarget.7809 Text en Copyright: © 2016 Sebagh et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Sebagh, Mylène
Allard, Marc-Antoine
Bosselut, Nelly
Dao, Myriam
Vibert, Eric
Lewin, Maïté
Lemoine, Antoinette
Cherqui, Daniel
Adam, René
Cunha, Antonio Sa
Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy
title Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy
title_full Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy
title_fullStr Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy
title_full_unstemmed Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy
title_short Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy
title_sort evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008308/
https://www.ncbi.nlm.nih.gov/pubmed/26943031
http://dx.doi.org/10.18632/oncotarget.7809
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