<prompt> A 56 year old Chronic smoker, mass in bronchusresected. Most useful immunohistochemical marker to make a proper diagnosis would be aEURCytokeratinVimentinEpithelial membrane cadherinLeucocyte common antigen  <response>: 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. Lets 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. CK7CK20 Urothelial transitional cell ca ; Ca pancreas, Ovarian macinous carcinoma CK7CK20- 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 HE2neu-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, CK56 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 Cajals interstitial cells. - These tumours respond to drug GlevacImatinib, 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 Hodgkins 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 