Neuroendocrine Markers: Positive differentiation of neuroendocrine breast carcinoma
A ‘marker‘ is a positive finding on a kind of diagnostic ‘tally-sheet‘, which indicates the presence of various proteins, hormones, unique cell-types, and other biological agents. There are many ways of testing for markers, but those most commonly used for neuroendocrine breast cancer include blood-serum levels, staining of tissue samples, chemical reactions, and even electron-microscope images.
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In order to be identified as ductal carcinoma with a neuroendocrine differentiation, positive neuroendocrine markers should be found on at least 50% of malignant cells. A histological evaluation of any breast tumor will routinely check for the presence of estrogen and progesterone receptors, the HER2/neu protein, also the GCDFP-15 protein, but for neuroendocrine breast tumors additional markers, uniquely associated with neuroendocrine cells, are considered. Chromogranin and synaptophysin, for example, are two proteins commonly secreted by neuroendocrine cells.
Neuron specific enolase as a marker for neuroendocrine breast cancer
Another neuroendocrine marker is neuron specific enolase. Also known as enolase 2, or ENO2, it is a uniquely human gene found in neurons (a ‘neuron‘ is electrically excitable cell, as in the brain and nervous system) and cells of neural origin. The ENO2 protein will certainly be found in neuroendocrine cells, but its presence alone is generally considered insufficient to confirm neuroendocrine differentiation in breast carcinoma. Most breast cancer experts call for at least 2 of 3 (chromogranin, synaptophysin, and enolase 2) if not all three, to be present in at least 50% of all malignant cells.
Polypeptides and Neuro-transmitters
The use of an electron microscope might seem a bit odd; but neuroendocrine cells are influenced by polypeptide hormones and neurotransmitters which are atomically distinguished by the the number of electrons orbiting an atom. The pathologist may also employ an ‘argyrophil stain‘ for this unique molecular context. ‘Argyrophillic‘ means ‘something which loves silver‘, or in other words a chemical which is highly reactive with silver. An argyrophil stain contains agents which can convert a silver-nitrate molecule into a metallic silver, which will then appear as a black deposit on the tissue sample.
Neuroendocrine markers contain amine-based proteins
What they are really testing for are neurotransmitters, which are chemical agents that relay or amplify signals between a neuron in one cell and a neuron in another cell. In a raw, molecular form they called ‘amines‘, which are nitrogen based atoms containing a ‘lone-pair‘ of orbiting electrons. This ‘lone-pair‘ of electrons results in a certain molecular instability and re-activeness, and these electrons have been found to influence the function of certain proteins.
‘Polypeptides‘ are the proteins and hormones released as a result of chemical activity in these ‘amine‘ molecules. The upshot of all of this is; neuroendocrine cells are full of these ‘amine-based‘ proteins, and if they are present in the tumor, they will be clearly revealed by the argyrophil stain.
Neuroendocrine markers are widely used in cancer diagnosis
Neuroendocrine markers help identify the origin of mutated cancer cells, not just in the breast, but in other parts of the body. Carcinoid carcinoma, which is a cancer of simple stem cells of neuroendocrine origin and tends to develop in the gut wall or appendix, is also diagnosed in part through the use of neuroendocrine markers. In fact, neuroendocrine carcinoma of the breast has only recently been classified as a unique ductal carcinoma, having previously been subsumed as a subset of carcinoid carcinoma. “Carcinoid carcinoma of the breast” is a term still occasionally used to imply “ductal carcinoma with neuroendocrine differentiation“, or simply “neuroendocrine breast cancer“.
For further reading, I suggest you visit this page on neuroendocrine carcinoma, go to this page on hormone receptor statuses of breast cancer, as well as this page for a brief overview of breast cancer treatments.
References
- Tse GM, Ma TK, Chu WC, Lam WW, Poon CS, Chan WC. Neuroendocrine differentiation in pure type mammary mucinous carcinoma is associated with favorable histologic and immunohistochemical parameters. Mod Pathol. 2004 May;17(5):568-72.
- Sapino A, Bussolati G. Is detection of endocrine cells in breast adenocarcinoma of diagnostic and clinical significance? Histopathology. 2002 Mar;40(3):211-4.
- Mardi K, Sharma J. Fine needle aspiration cytology of breast carcinoma with neuroendocrine features–a case report with histopathological and immunohistochemical correlation. Indian J Pathol Microbiol. 2007 Jan;50(1):65-8.
- Salman WD, Harrison JA, Howat AJ.Small-cell neuroendocrine carcinoma of the breast. J Clin Pathol.(Aug. 2006);59(8):888.
- Oliveira AM, Tazelaar HD, Myers JL, Erickson LA, Lloyd RV.Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol.Jun 2001 ;25(6):815-9.
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