Using Myoepithelial cell markers for breast cancer staging

A 'marker' is one of a number of diagnostic indicators a pathologist will use to obtain a clear, differentiated indentification of a particular tissue sample. By doing certain tests which effect the myoepithelial cells of a given sample, it is possible to determine the current 'status' ( in situ, infiltrating, or invasive ) of a ductal lesion. Myoepithelial cells, which are found many places in the body, are 'contractile' which means they can function to forcibly express or 'squeeze-out' the contents of a gland. They are typically situated 'lower' in a gland; in between the secretory cells themselves and the basement membrane. In the breast, the myoepithelial cells are located 'in the middle', above the basal layer and just below the top layer of secretory cells at the duct wall. The myoepithelial cells help 'squeeze' the contents (milk) of the secretory cells into the duct. Normally, the presense of myoepithelial cells in a histological workup is an inconspicuous finding. However, presense of reduced or under-stress myoepithelial cells in the context of a suspected breast cancer can be of concern, and may indicate a transition to infiltrating and possibly invasive status.

breast myoepithelial cells

Types of myoepithelial markers

There are many different kinds of markers used in breast cancer diagnosis, but the most common are protein-based dyes that detect the presence of hormones, hormone receptors, and other proteins which are released as cells grow, interact, and decay. Myoepithelial markers are obtained through the use of certain of these protein-based dyes.

luminal to myopithelial ratio.

It is generally accepted that primary breast carcinomas will show an increase in the number of luminal (duct-wall) cells and a decrease in the number of myoepithelial cells. Sometimes this is called the luminal-to-myoepithelial ratio. As a breast cancer evolves from in-situ, to infiltrating, and finally to invasive status, the relative number of myoepithelial cells drops off to essentially nothing. 'Luminal' markers test for the presense of specific proteins given off during growth of these luminal cells. If the finding is for larger than normal numbers of luminal cells, it suggest that myoepithelial cells are diminishing in number, and there is cause for concern.

Increased basal membrane cells, myoepithelial cells under stress

Laminin-1 is a hormone released in the growth of basal membrane cells, and it's presense in normal amounts has been traditionally seen as a marker for the absense of invasive breast cancer. (Basal cells are 'at the bottom', myoepithelial cells 'in the middle' and luminal cells ' at the top' or right at the duct wall ) An unanticipated increase in the number of basal membrane cells suggests that cancer or perhaps some other disease has disrupted the normal cellular balance. Basal cells are increasing in number because myoepithelial cells are decreasing in number, and this means the carcinoma is no longer in situ.

Other proteins like CK14, CK17, and vimentin are normally associated with healthy myoepithelial cells. Vimentin is a kind of 'filament' protein which helps to give a cell strength and flexibility. However, if one finds CK14, CK17, and vimentin in a higher-than-normal numbers, it suggests that cell integrity is failing, releasing these proteins into the blood stream. Studies show that vimentin is present in up to 30% of all invasive breast carcinomas.

A proportional balance of growth and decay indicators

So we can see how a proportional balance of markers for proteins and hormones associated with growth, or decay, of the different breast cells can give a clearer picture and to an extent 'predict' the progression of the carcinoma. Some breast cancer researchers feel that the worst prognosis is for basal-like breast cancers (tumors where basal membrane cells are increased in number) with negative estrogen receptor status, but which also show an expression of both luminal and myoepithelial cell markers. This is a relatively new approach to breast cancer diagnosis and staging, and there is hope that by identifying and grouping the different proportional presentations of basal, myoepithelial, and luminal cells ( now thought to break into four categories) an even more accurate prediction of cancer behaviour can be obtained, which will in turn lead to better treatments and higher survival rates.

Note: The basal-cell growth indicators dicussed here refer to ductal carcinoma, in which there are declining numbers of myoepithelial cells beneath the breast ducts. This is NOT to be confused with "basal-cell" skin cancer, which is characterized by mutations and proliferations of squamous skin cells.

References

  1. Rønnov-Jessen L, Petersen OW, Bissell MJ. Cellular changes involved in conversion of normal to malignant breast: Importance of the stromal reaction. Physiol Rev. 1996;76:69–125
  2. Wetzels RH, Holland R, van Haelst UJ, Lane EB, Leigh IM, Ramaekers FC. Detection of basement membrane components and basal cell keratin 14 in noninvasive and invasive carcinomas of the breast. Am J Pathol. 1989;134:571–9.
  3. Gudjonsson, Thorarinn, Adriance, Melissa C., Sternlicht, Mark D., Petersen, Ole W., and Bissell, Mina J. Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia. Journal of Mammary Gland Biology and Neoplasia.Volume 10, Number 3 / July, 2005. p. 261-272 .
  4. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.
  5. Rudland PS. Stem cells and the development of mammary cancers in experimental rats and in humans. Cancer Metastasis Rev. 1987;6:55–83.
  6. Fulford, L. G., Reis-Filho, J. S., Ryder, K., Jones, C., Gillett, C. E., Hanby, A., Easton, D. and Lakhani, S. R. (2007-01-11) Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Research, 9 1: 1-11.

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Copyright Steven B. Halls, MD Last edited 12-February-2010

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