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Non-randomness of the anatomical distribution of tumors

BACKGROUND: Why does a tumor start where it does within an organ? Location is traditionally viewed as a random event, yet the statistics of the location of tumors argues against this being a random occurrence. There are numerous examples including that of breast cancer. More than half of invasive br...

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Autores principales: Yu, Clare, Mitchell, James Kameron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876694/
https://www.ncbi.nlm.nih.gov/pubmed/29623957
http://dx.doi.org/10.1186/s41236-017-0006-7
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author Yu, Clare
Mitchell, James Kameron
author_facet Yu, Clare
Mitchell, James Kameron
author_sort Yu, Clare
collection PubMed
description BACKGROUND: Why does a tumor start where it does within an organ? Location is traditionally viewed as a random event, yet the statistics of the location of tumors argues against this being a random occurrence. There are numerous examples including that of breast cancer. More than half of invasive breast cancer tumors start in the upper outer quadrant of the breast near the armpit, even though it is estimated that only 35 to 40% of breast tissue is in this quadrant. This suggests that there is an unknown microenvironmental factor that significantly increases the risk of cancer in a spatial manner and that is not solely due to genes or toxins. We hypothesize that tumors are more prone to form in healthy tissue at microvascular ‘hot spots’ where there is a high local concentration of microvessels providing an increased blood flow that ensures an ample supply of oxygen, nutrients, and receptors for growth factors that promote the generation of new blood vessels. RESULTS: To show the plausibility of our hypothesis, we calculated the fractional probability that there is at least one microvascular hot spot in each region of the breast assuming a Poisson distribution of microvessels in two-dimensional cross sections of breast tissue. We modulated the microvessel density in various regions of the breast according to the total hemoglobin concentration measured by near infrared diffuse optical spectroscopy in different regions of the breast. Defining a hot spot to be a circle of radius 200 μm with at least 5 microvessels, and using a previously measured mean microvessel density of 1 microvessel/mm(2), we find good agreement of the fractional probability of at least one hot spot in different regions of the breast with the observed invasive tumor occurrence. However, there is no reason to believe that the microvascular distribution obeys a Poisson distribution. CONCLUSIONS: The spatial location of a tumor in an organ is not entirely random, indicating an unknown risk factor. Much work needs to be done to understand why a tumor occurs where it does. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41236-017-0006-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-58766942018-04-03 Non-randomness of the anatomical distribution of tumors Yu, Clare Mitchell, James Kameron Cancer Converg Research BACKGROUND: Why does a tumor start where it does within an organ? Location is traditionally viewed as a random event, yet the statistics of the location of tumors argues against this being a random occurrence. There are numerous examples including that of breast cancer. More than half of invasive breast cancer tumors start in the upper outer quadrant of the breast near the armpit, even though it is estimated that only 35 to 40% of breast tissue is in this quadrant. This suggests that there is an unknown microenvironmental factor that significantly increases the risk of cancer in a spatial manner and that is not solely due to genes or toxins. We hypothesize that tumors are more prone to form in healthy tissue at microvascular ‘hot spots’ where there is a high local concentration of microvessels providing an increased blood flow that ensures an ample supply of oxygen, nutrients, and receptors for growth factors that promote the generation of new blood vessels. RESULTS: To show the plausibility of our hypothesis, we calculated the fractional probability that there is at least one microvascular hot spot in each region of the breast assuming a Poisson distribution of microvessels in two-dimensional cross sections of breast tissue. We modulated the microvessel density in various regions of the breast according to the total hemoglobin concentration measured by near infrared diffuse optical spectroscopy in different regions of the breast. Defining a hot spot to be a circle of radius 200 μm with at least 5 microvessels, and using a previously measured mean microvessel density of 1 microvessel/mm(2), we find good agreement of the fractional probability of at least one hot spot in different regions of the breast with the observed invasive tumor occurrence. However, there is no reason to believe that the microvascular distribution obeys a Poisson distribution. CONCLUSIONS: The spatial location of a tumor in an organ is not entirely random, indicating an unknown risk factor. Much work needs to be done to understand why a tumor occurs where it does. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41236-017-0006-7) contains supplementary material, which is available to authorized users. Springer International Publishing 2017-12-19 2017 /pmc/articles/PMC5876694/ /pubmed/29623957 http://dx.doi.org/10.1186/s41236-017-0006-7 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research
Yu, Clare
Mitchell, James Kameron
Non-randomness of the anatomical distribution of tumors
title Non-randomness of the anatomical distribution of tumors
title_full Non-randomness of the anatomical distribution of tumors
title_fullStr Non-randomness of the anatomical distribution of tumors
title_full_unstemmed Non-randomness of the anatomical distribution of tumors
title_short Non-randomness of the anatomical distribution of tumors
title_sort non-randomness of the anatomical distribution of tumors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876694/
https://www.ncbi.nlm.nih.gov/pubmed/29623957
http://dx.doi.org/10.1186/s41236-017-0006-7
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