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. 2005 Nov 28;93(11):1244-9.
doi: 10.1038/sj.bjc.6602848.

Spread of human cancer cells occurs with probabilities indicative of a nongenetic mechanism

J S Michaelson  1 , J A Cheongsiatmoy, F Dewey, M J Silverstein, D Sgroi, B Smith, K K Tanabe
Affiliations

Spread of human cancer cells occurs with probabilities indicative of a nongenetic mechanism

J S Michaelson et al. Br J Cancer. .

Abstract

There has been much uncertainty as to whether metastasis requires mutation at the time of spread. Here, we use clinical data to calculate the probability of the spread of melanoma and breast cancer cells. These calculations reveal that the probability of the spread of cancer cells is relatively high for small tumours (approximately 1 event of spread for every 500 cells for melanomas of 0.1 mm) and declines as tumours increase in size (approximately 1 event of spread for every 10(8) cells for melanomas of 12 mm). The probability of spread of breast cancer cells from the lymph nodes to the periphery is approximately 1 event of spread for every 10(8) cells in the nodal masses, which have a mean diameter of 5 mm, while the probability of spread of cancer cells from the breast to the periphery when the primary masses are 5 mm is also approximately 1 event of spread for every 10(8) cells. Thus, the occurrence of an event of spread from the breast to the lymph nodes appears not to increase the propensity of the progeny of those cells to spread from the lymph nodes to the periphery. These values indicate that the spread of human breast cancer and melanoma cells is unlikely to occur by a mechanism requiring mutation at the time of spread.

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Figures

Figure 1
Figure 1
Calculations of the probability of lethal spread of breast cancer and melanoma cells, as a function of tumour size, and the close fit of the data to equation (2). (R2=0.98 for breast cancer, (R2=0.9 for melanoma). Shown here are the overall values for the probability of lethal spread of cancer cells from the primary site to the periphery for breast cancer (pBC-overall) and melanoma (pMEL-overall) using tumour size/survival data for all patients (Table 1). Note the close fit to the power function, equation (3).
Figure 2
Figure 2
Calculations of the probability of lethal spread of breast cancer from the primary site to the periphery (pBC-overall) by equation (2) and using tumour size/survival data for all patients (Table 1), and the probability of nonlethal spread of breast cancer from the primary site to the lymph nodes (pBC-to-nodes) by equation (2) and using tumour size/nodal status data (Table 1). Note that in both cases the relationship between the probability of spread and tumour size is well fit by a power function, equation (3).
Figure 3
Figure 3
Schematic of Geometrical Model #1. Shown is a highly idealised image of a tumour mass and a lymph duct leading to a local lymph node.
See this image and copyright information in PMC

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