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Non-randomness of the anatomical distribution of tumors.

ABSTRACT: 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.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 ?m 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.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.

SUBMITTER: Yu C

PROVIDER: S-EPMC5876694 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Non-randomness of the anatomical distribution of tumors.

Yu Clare C Mitchell James Kameron JK

Cancer convergence 20171219 1

<h4>Background</h4>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 ther ...[more]

PMID: 29623957

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Project description:Vertebrobasilar dolichoectasia (VBD) is a dilatative arteriopathy associated with intracerebral hemorrhage. In the present study, we sought to evaluate the frequency and anatomical distribution of cerebral microbleeds (cMBs) and intracerebral hemorrhage (ICH) in VBD.From a MRI database 94 VBD patients were identified and analyzed with special emphasis on cMBs and ICH on T2*-weighted gradient echo images (GRE) in relation to the established diagnostic MRI criteria of VBD (diameter, height, and lateral position). cMBs/ICH location was categorized into anterior/posterior circulation. Clinical information like demographic details, clinical symptoms, and comorbidities were abstracted from the case records. An extensive modelling approach using generalized linear mixed-effects models was used.Overall, 79 (84.0%) patients (mean age 72.1±10.0 years, 74.7% male) with a standard stroke MRI protocol including T2*-weighted images were included in the analysis. cMBs were observed in 38/79 (48.1%) patients, ranging from 1 to 84 cMBs per patient. In the posterior circulation cMBs were observed more frequently (34/38 (89.5%)) in comparison to the anterior circulation (24/38 (63.2%)). cMBs were observed in the thalamus in 20/38 (52.6%), hippocampus in 1/38 (2.6%), occipital lobe in 18/38 (47.4%), pons in 6/38 (15.8%), medulla oblongata in 2/38 (5.2%), and cerebellum in 14/38 (36.8%) patients. ICH was observed in only 6/79 (7.6%) patients. There were significantly more cMBs in the posterior- (NCMBs-PC = 1.717, 95%CI: 1.336-2.208, p = 0.0315) than in the anterior circulation. Logistic regression model showed a significant positive effect of clinical symptoms such as ischemic, TIA and hemorrhagic stroke on the presence of cMBs (OR = 3.34, 95%CI [2.0-5.57], p = 0.0184; ndf = 78, AIC = 107.51). General linear model showed that clinical symptoms have a highly significant effect on the number of cMBs (N = 2.78, 95%CI [2.51-3.07], p<2*10-16; ndf = 78, AIC = 1218).cMBs and ICH may be observed in the anterior and posterior circulation in VBD but they occur more frequently in the posterior circulation. Most common anatomical locations of cMBs in VBD were the thalamus, occipital lobe and cerebellum. This posterior dominance of cMBs and ICH in VBD might reflect a specific underlying vascular pathology.

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Non-randomness of the anatomical distribution of tumors.

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Non-randomness of the anatomical distribution of tumors.

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