Difference between revisions of "Course:Introduction to Neuropathology"

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Source: Partly from https://en.wikipedia.org/wiki/Cytokeratin and modified accordingly
(→‎Molecular neuropathology: Source: https://en.wikipedia.org/wiki/Ki-67_%28protein%29)
(Source: Partly from https://en.wikipedia.org/wiki/Cytokeratin and modified accordingly)
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===Day 2===
===Day 2===
====Antibodies in neurooncology====
The exact classification of brain tumours is essential for proper treatment of patients. Although morphological evalutaion of the [[H&E]] stained tumour specimen is a crucial first step, subsequent immunhistochemical stains and molecular analyses help to secure the diagnosis. The following five antibodies: GFAP, [[MAP2]], [[ATRX]], [[IDH-1]], pan-Cytokeratin and Ki-67 (MiB-1) allow for good classification of the most common tumours observed in the brain. A short introduction:
The exact classification of brain tumours is essential for proper treatment of patients. Although morphological evalutaion of the [[H&E]] stained tumour specimen is a crucial first step, subsequent immunhistochemical stains and molecular analyses help to secure the diagnosis. The following five antibodies: GFAP, [[MAP2]], [[ATRX]], [[IDH-1]], pan-Cytokeratin and Ki-67 (MiB-1) allow for good classification of the most common tumours observed in the brain. A short introduction:
* Ki-67 (Kiel-67, clone MiB-1 which stands for Made in Borstel) is a nuclear protein that is associated with cellular proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0).<ref name="pmid10653597">{{Cite journal  | last1 = Scholzen | first1 = T. | last2 = Gerdes | first2 = J. | title = The Ki-67 protein: from the known and the unknown. | journal = J Cell Physiol | volume = 182 | issue = 3 | pages = 311-22 | month = Mar | year = 2000 | doi = 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9 | PMID = 10653597 }}</ref> Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. <ref>https://en.wikipedia.org/wiki/Ki-67_%28protein%29</ref> An [[astrocytoma]] with 2% positive tumor cells is growing considerably slower than a [[glioblastoma]] with a labelling index of 20%. Cells with a quick turnover therefore serve as good positive controls for this antibody.
* '''Ki-67''' (Kiel-67, clone MiB-1 which stands for Made in Borstel) is a nuclear protein that is associated with cellular proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0).<ref name="pmid10653597">{{Cite journal  | last1 = Scholzen | first1 = T. | last2 = Gerdes | first2 = J. | title = The Ki-67 protein: from the known and the unknown. | journal = J Cell Physiol | volume = 182 | issue = 3 | pages = 311-22 | month = Mar | year = 2000 | doi = 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9 | PMID = 10653597 }}</ref> Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. <ref>https://en.wikipedia.org/wiki/Ki-67_%28protein%29</ref> An [[astrocytoma]] with 2% positive tumor cells is growing considerably slower than a [[glioblastoma]] with a labelling index of 20%. Cells with a quick turnover therefore serve as good positive controls for this antibody.
*  
 
* '''panCK''' (MNF-116) Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of eukaryontic epithelial tissue and their derived tumours. The 20 different cytokeratins can be divided into low versus high molecular weight solely based on their molecular weight.  The current cocktail detects almost all types of epithelial, from simple glandular to stratfied squamous epithelia and therefore is ideal to detect malignant epithelial tumours ([[carcinoma]]s). Rarely a cross-reaction with dendritic cells in the tonsil or smooth muscle cells of vessels is observed. Most brain metastases are carcinomas of breast, lung or prostrate and therefore stain intensely for pan-cytokeratin. In contrast, glial and neuronal brain tumours as well as melanomas do not stain for this marker. Expression of these cytokeratin types is frequently organ or tissue specific. Pathologists employ different cytokeratins to detect the cell of origin of various tumors.  As an example, [[Cytokeratin_7|CK7]] is typically expressed in the ductal epithelium of the genitourinary  tract and [[Cytokeratin_20|CK20]] most commonly in the gastrointestinal tract. Best results are obtained with Trypsin or Pronase pretreatment for antigen demasking. Normal epithelial tissue (gut, skin) may serve as positive control.


A descriptive overview of various brain tumours is found [[Neuropathology tumours|here]].
A descriptive overview of various brain tumours is found [[Neuropathology tumours|here]].
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