Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma

Abstract Background Despite decades of research, the early phases of metastatic development are still not fully understood. Canine osteosarcoma (OS) is a highly aggressive cancer, with a high metastatic rate (> 90%), despite a low overt metastatic prevalence at initial diagnosis (< 15%). Canin...

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Autores principales:	Mikael Kerboeuf, Erling Olaf Koppang, Anita Haug Haaland, Frode Lingaas, Øyvind Sverre Bruland, Jon Teige, Lars Moe
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Bone cancer Canine Lung metastasis Metastasis model Pulmonary metastasis Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/a35947d1fc004ce0acd27ae62b1d0c74
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spelling	oai:doaj.org-article:a35947d1fc004ce0acd27ae62b1d0c742021-11-08T11:03:52ZEarly immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma10.1186/s13028-021-00608-91751-0147https://doaj.org/article/a35947d1fc004ce0acd27ae62b1d0c742021-11-01T00:00:00Zhttps://doi.org/10.1186/s13028-021-00608-9https://doaj.org/toc/1751-0147Abstract Background Despite decades of research, the early phases of metastatic development are still not fully understood. Canine osteosarcoma (OS) is a highly aggressive cancer, with a high metastatic rate (> 90%), despite a low overt metastatic prevalence at initial diagnosis (< 15%). Canine OS is generally regarded as a good clinically relevant model for human OS. The aim of this hypothesis-generating study was to evaluate a method to detect pulmonary micrometastases and study their prevalence in dogs with OS without macroscopic metastases. We prospectively enrolled dogs with OS that received no cancer-specific treatment (n = 12) and control dogs without cancer (n = 2). Dogs were necropsied and sampled immediately after euthanasia. The OS dogs were classified as having macroscopic metastases (n = 2) or not (n = 10). We immunohistochemically stained one tissue sample from each of the seven lung lobes from each dog with a monoclonal antibody (TP-3) to identify micrometastases (defined as clusters of 5–50 tumour cells), microscopic metastases (> 50 tumour cells) and TP-3 positive single cells (< 5 tumour cells). Results We showed that pulmonary micrometastases easily overseen on routine histology could be detected with TP-3. Pulmonary micrometastases and microscopic metastases were present in two dogs with OS without macroscopic metastases (20%). Micrometastases were visualised in three (43%) and four (57%) of seven samples from these two dogs, with a mean of 0.6 and 1.7 micrometastases per sample. Microscopic metastases were present in one (14%) and four (57%) of seven samples from the same two dogs, with a mean of 0.14 and 1.0 microscopic metastases per sample. There were four (57%) and two (29%) samples with neither microscopic metastases nor micrometastases for each of these two dogs. The prevalence of pulmonary micrometastases (20%) was significantly lower than expected (> 90%) based on commonly expected metastatic rates after amputation (P < 0.0001). There was no statistically significant difference in the number of TP-3 positive single cells in between groups (P = 0.85). Conclusions Pulmonary micrometastases could be detected with TP-3 immunohistochemistry in a subset of dogs with OS before macroscopic metastases had developed. We propose that dogs with spontaneous OS represent clinically relevant models to study early micrometastatic disease.Mikael KerboeufErling Olaf KoppangAnita Haug HaalandFrode LingaasØyvind Sverre BrulandJon TeigeLars MoeBMCarticleBone cancerCanineLung metastasisMetastasis modelPulmonary metastasisVeterinary medicineSF600-1100ENActa Veterinaria Scandinavica, Vol 63, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bone cancer Canine Lung metastasis Metastasis model Pulmonary metastasis Veterinary medicine SF600-1100
spellingShingle	Bone cancer Canine Lung metastasis Metastasis model Pulmonary metastasis Veterinary medicine SF600-1100 Mikael Kerboeuf Erling Olaf Koppang Anita Haug Haaland Frode Lingaas Øyvind Sverre Bruland Jon Teige Lars Moe Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma
description	Abstract Background Despite decades of research, the early phases of metastatic development are still not fully understood. Canine osteosarcoma (OS) is a highly aggressive cancer, with a high metastatic rate (> 90%), despite a low overt metastatic prevalence at initial diagnosis (< 15%). Canine OS is generally regarded as a good clinically relevant model for human OS. The aim of this hypothesis-generating study was to evaluate a method to detect pulmonary micrometastases and study their prevalence in dogs with OS without macroscopic metastases. We prospectively enrolled dogs with OS that received no cancer-specific treatment (n = 12) and control dogs without cancer (n = 2). Dogs were necropsied and sampled immediately after euthanasia. The OS dogs were classified as having macroscopic metastases (n = 2) or not (n = 10). We immunohistochemically stained one tissue sample from each of the seven lung lobes from each dog with a monoclonal antibody (TP-3) to identify micrometastases (defined as clusters of 5–50 tumour cells), microscopic metastases (> 50 tumour cells) and TP-3 positive single cells (< 5 tumour cells). Results We showed that pulmonary micrometastases easily overseen on routine histology could be detected with TP-3. Pulmonary micrometastases and microscopic metastases were present in two dogs with OS without macroscopic metastases (20%). Micrometastases were visualised in three (43%) and four (57%) of seven samples from these two dogs, with a mean of 0.6 and 1.7 micrometastases per sample. Microscopic metastases were present in one (14%) and four (57%) of seven samples from the same two dogs, with a mean of 0.14 and 1.0 microscopic metastases per sample. There were four (57%) and two (29%) samples with neither microscopic metastases nor micrometastases for each of these two dogs. The prevalence of pulmonary micrometastases (20%) was significantly lower than expected (> 90%) based on commonly expected metastatic rates after amputation (P < 0.0001). There was no statistically significant difference in the number of TP-3 positive single cells in between groups (P = 0.85). Conclusions Pulmonary micrometastases could be detected with TP-3 immunohistochemistry in a subset of dogs with OS before macroscopic metastases had developed. We propose that dogs with spontaneous OS represent clinically relevant models to study early micrometastatic disease.
format	article
author	Mikael Kerboeuf Erling Olaf Koppang Anita Haug Haaland Frode Lingaas Øyvind Sverre Bruland Jon Teige Lars Moe
author_facet	Mikael Kerboeuf Erling Olaf Koppang Anita Haug Haaland Frode Lingaas Øyvind Sverre Bruland Jon Teige Lars Moe
author_sort	Mikael Kerboeuf
title	Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma
title_short	Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma
title_full	Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma
title_fullStr	Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma
title_full_unstemmed	Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma
title_sort	early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a35947d1fc004ce0acd27ae62b1d0c74
work_keys_str_mv	AT mikaelkerboeuf earlyimmunohistochemicaldetectionofpulmonarymicrometastasesindogswithosteosarcoma AT erlingolafkoppang earlyimmunohistochemicaldetectionofpulmonarymicrometastasesindogswithosteosarcoma AT anitahaughaaland earlyimmunohistochemicaldetectionofpulmonarymicrometastasesindogswithosteosarcoma AT frodelingaas earlyimmunohistochemicaldetectionofpulmonarymicrometastasesindogswithosteosarcoma AT øyvindsverrebruland earlyimmunohistochemicaldetectionofpulmonarymicrometastasesindogswithosteosarcoma AT jonteige earlyimmunohistochemicaldetectionofpulmonarymicrometastasesindogswithosteosarcoma AT larsmoe earlyimmunohistochemicaldetectionofpulmonarymicrometastasesindogswithosteosarcoma
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Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma

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