A 56 year old Chronic smoker, mass in bronchusresected. Most useful immunohistochemical marker to make a proper diagnosis would be aEUR’
Correct Answer: Cytokeratin
Description: Cytokeratin Immunohistochemistry Immunohistochennstry is an impoant tool for determination of type of tissue by the presence (or absence) of tissue specific lineage markers. Basic principle of immunohistochemistty is to label an antibody with a probe (coloured marker) which is specific to an antigen of a paicular tissue. - This antibody is run on the tissue of unknown origin. If the tissue has that paicular antigen site (epitope), then the antibody will get attached to the tissue. Because this antibody is labeled, it can be seen under a microscope and the origin of the tissue can be diagnosed. Let's begin the discussion with intermediate filaments: Intermediate filaments are cytoskeleton components of both normal and neoplastic tissue. There are the major antigens used in immunohistochemistry. Five broad classes of intermediate filaments exist. Most neoplasms show a predominant expression of one of these: a) Keratins Carcinomas, mesothelioma and non? seminomous GCT b) Vimentin Sarcoma, melanomas, seminomas, lymphomas c) Neurofilament Neural and neuroendocrine tumours d) Glial fibrillary acidic protein (GFAP) Neoplasms of astroglial origin e) Desmin Tumours of muscular origin (leiomyoma and rhabdomyomas) Neoplastic cells can co-express more than one of these intennediate filaments i.e. they may be +ve for 2 markers of different origin. These .findings can also be helpful to diagnose a tumour. After this brief outline let us examine various markers in each neoplasia. Carcinomas Cytokeratins are the most sensitive markers for carcinoma. - These are. fuher subdivided into 20 subtypes based on molecular weight and isoelectric pH. - These individual keratins provide impoant information about site of origin of given carcinoma. CK7+/CK20+ Urothelial transitional cell ca ; Ca pancreas, Ovarian macinous carcinoma CK7+/CK20- Breast, lung, endometrium, thyroid, ovary (serous), thymoma CK7-/CK20+ Colorectal, stomach, Merkel cell CK7-/CK20- Liver, kidney (clear cell), prostate Epithelial markers for determination of site of origin of carcinoma Breast * Estrogen and progesterone receptor (ifpositive, denotes good prognosis) * GCDP (gross cystic disease protein) specific breast marker * (HE2/neu-poor prognosis) * Cadherin is -ye in lobular carcinoma but +ve in ductal carcinoma Liver CAM, AFP Thyroid Thyroglobul in (papillary & follicular) calcitonin (medullary) Prostate PAP, prostate specific antigen Colorectal CEA, CK20, pancreas CA19-9, ovary CA-125 Other epithelial markers Epithelial membrane antigen (EMA) -4 Breast, lung and kidneys, adenocarcinoma are typically +ve. Carcinoma embryonic antigen +ve in carcinomas of GIT, pancreas, lung, breast, uterus and ovary Keratin positive tumours besides carcinomas Mesotheliomas - Usually +ve HMW keratin, CK5/6 should be distinguished from adenocarcinomas which are protective for low molecular weight cytokeratin and carcinoma embryonic origin. Non-seminomatous GCT - These can be distinguished from carcinoma as they are positive for - HCG (choriocarcinoma) - AFP (endothelial sinus tumour), - Placental alkaline phosphatase (PCAP), - Embryonal Ca (choriocarcinoma and endodennal sinus tumour). Sarcomas Vimentin: -Characteristically expressed in normal mesenchymal cells - Such tumours would include tumors derived from - blood vessels, - muscle, - fat, - cailage, - hemopoietic elements, - neural tube & neural crest, and - Seoli & Granulosa cells of testis and ovary. Other markers used in mesenchymal cell tumours. Tumour of myogenous origin, i.e. leio and rhabdomyosarcoma - Muscle specific Actin & Desmin - Myoglobin, myogenin and myo-D1 Tumour of vascular origin, i.e. hemangioma and angiosarcoma - Factor VIII - CD31 Fibrohistiocytic tumors, e.g. malignant fibrous histiocytoma - CD68 - HAM56 Osteosarcoma: - Osteopontin - Osteocalcin - Osteonectin - Bone GIA protein Ewing Sarcoma and PNET (Ewing in soft tissue): - CD99 (antibodies against MIC-2 gene) - besides Ewings this is also positive in few other tumours including ovarian granulosa cell tumour. GIST (gastrointestinal stromal tumours): - CD117 identifies C-KIT gene for tyrosine kinase. - These are normally present on Cajal's interstitial cells. - These tumours respond to drug Glevac/Imatinib, which is also given to patients of CML having (9:22) translocation. Other impoant tumours where immunohistochemistry has a role: Melanomas -S-100 (sensitive but not specific marker) - HMB-45 (melanosome, highly sensitive and specific) Lymphomas -CD-45 - used in screening of lymphomas. - Fuher typing is done by: - B cell markers CD19, CD20, CD23 - T-cell markers CD-2, CD-3, CD-7 - Reedsternberg cells - CD15 & CD30 .for Hodgkin's lymphoma Seminoma -Vimentin & PLAP +ve - AFP and HCG (-ye) Neuroendocrine tumour, e.g. carcinoid tumors -NSE (neuron specific enolase) - Chromogranin - Synaptophysin - Leu-7 Neural tumours of glial origin, e.g. Astrocvtomas -GFAP (Glial fibrillary acid protein)
Category:
Pathology
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