Abstract
BackgroundWhy 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.ResultsTo 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/mm2, 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.ConclusionsThe 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.
Highlights
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
In the supplement (Additional file 1), we show that our results are rather insensitive to the radius of a hot spot and to the minimum number of microvessels in a hot spot as long as n ≥ 4
For n < 4, it is easy to meet the requirements for a microvascular hot spot and there is a high probability that every region of the breast will have at least one hot spot
Summary
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. 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. If we divide the colon at the splenic flexure into a proximal and a distal section (and exclude the rectum), colon cancer tends to be found in the proximal, rather than in the distal, part of the colon even though these two sections are roughly the same length. It should be noted that the proximal and distal colon differ in terms of development (embryology), physiology, and molecular biology (Gervaz et al, 2004) but it is not clear whether any of these differences can account for the preference of tumors to occur in the proximal colon
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