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    [0] => 
    [1] => department-of-laboratory-and-transfusion-services
    [2] => histopathology-cytopathology
    [3] => diagnostic-theranostic-markers
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Diagnostic and Theranostic Markers

Immunohistochemistry

Immunohistochemistry (IHC) has evolved and expanded its use in pathology from diagnosis and classification, to predictive and prognostic utility. Our laboratory provides a wide range of these markers.

  • Breast

Specific marker for breast carcinoma, GATA-3 and Mammaglobin, helps in confirmation of origin, especially in metastatic sites. Androgen Receptor (AR) immunoexpression is also being done triple negative breast cancer (TNBC).

  • Bone and Soft tissue

IHC marker H3F3A (Histone 3.3) G34W is used as a surrogate marker for H3.3 mutations, which helps in confirming primary benign and malignant giant cell tumor (GCT) of bone, and distinguish it from other mimics like giant cell osteosarcoma, which has major therapeutic implications.

IHC for HHV-8 (Human herpesvirus-8), is available for diagnosing Kaposi sarcoma.

IHC for H3K27me3 is available for diagnosing malignant peripheral nerve sheath tumors (high grade and radiation induced MPNST), which suggests loss of PRC2 pathway as the underlying molecular mechanism.

Specific IHC for CDK4 & MDM-2 are available for diagnosing parosteal osteosarcoma (OS), intramedullary low grade OS, and liposarcoma (well differentiated & de-differentiated liposarcomas).

IHC marker NKX2.2 is a sensitive and specific marker for diagnosing Ewings’ sarcoma, and forms a target of EWS-FLI-1 fusion protein.

IHC for INI-1, marker or SMARB1 gene, is done for diagnosing the aggressive extrarenal rhabdoid tumors.

  • Central nervous System (CNS)/Brain

IHC is performed in CNS tumors to assist the diagnosis, prognosis, and predict therapeutic response.

The IHC biomarkers performed at our laboratory include ATRX, IDH1 (R132H), TP53 and BRAF V600E, which assist in classifying glial tumors.

Medulloblastomas are classified into appropriate genetic groups by IHC using beta-catenin, YAP1, and GAB1, and p53 immunostaining.

Ependymoma specific IHC include L1CAM and YAP1. H3K27M, used to classify high grade midline gliomas, is also available in our armamentarium.

IHC for SMARCB1/INI1 is used to identify atypical teratoid/rhabdoid tumors (AT/RT), which have a significantly different treatment regime from other CNS embryonal malignancies.

  • Female genital tract

A panel of IHC markers is required for diagnosis and characterization of cervix, endometrial and ovarian carcinomas (at the primary and metastatic site) including PAX-8, ER, p53, p16, WT-1 and Napsin-A.

IHC for L1CAM and HER2 are the upcoming markers used for prognostication of endometrial carcinomas. IHC for mismatch repair (MMR) proteins (discussed later) are performed in endometrioid adenocarcinomas to identify cases with Lynch Syndrome.

IHC marker p16 is routinely performed in cervical carcinomas as a surrogate marker for HPV (human papilloma virus) association.

  • Gastrointestinal tract

Periampullary carcinomas: IHC panel including for CK20, CDX2, MUC1 and MUC2 is used to subclassify periampullary carcinomas into pancreatobiliary and intestinal type adenocarcinomas.

IHC for SMAD-4 (DPC4) gene is done in pancreatic carcinomas.

  • Head and Neck Squamous cell carcinomas

P16 IHC as a surrogate marker for HPV positive in oropharyngeal carcinomas.

NUT IHC for NUT-carcinomas

  • Lymphomas

Apart from the routine IHC markers for diagnosing lymphoproliferative disorders and lymphomas, we have updated our armamentarium with new markers with diagnostic and prognostic utility- LMO2, MNDA, TBET, GATA3, c-myc, EBER-ISH (in-situ-hybridization), and HHV-8 (for castleman disease).

  • Neuroendcrine Tumors

INSM-1 (Insulinoma associated protein-1) is a new marker for neuroendocrine differentiation (others being synaptophysin, chromogranin and CD56). INSM-1 is a reliable, sensitive and highly specific marker for neuroendocrine differentiation in tumors of various organs.

  • Prostate

NKX3.1 is an androgen regulated prostatic tumor suppressor gene, and staining for protein is performed for diagnosing prostatic origin, especially at the metastatic sites. It is a highly sensitive and specific marker.

  • Renal Tumors

A panel of IHC markers are performed for confirmation of renal cell carcinomas (RCC), most common being the clear cell carcinoma, using CA-IX, CD10, CK7, and AMACR.

IHC marker SDH-B is performed to identify cases SDH-B deficient RCC.

IHC 2-SC (2-succinocysteine) and FH is available to identify Fumarate hydratase (FH) deficient RCC which are aggressive hereditary tumors; and TFE-3 and TFE-B for Mit Family of RCC.

  • Thoracic tumors

BRG-1 (SMARCA4) as a prognostic marker in …

Theranostic and prognostic biomarkers

Discipline of immunohistochemistry for the surgical pathologist has been evolving rapidly, and it also has theranostic and genomic applications. IHC has been adapted to the identification and demonstration of both prognostic and predictive markers.

The term “theranostics” is used to describe the proposed process of diagnostic therapy for individual patients and to tailor a treatment for them based on a test result.

  • Hormonal Receptors [Estrogen Receptor (ER),Progesterone Receptor (PR)]

Breast Carcinomas– Hormone receptors {Estrogen receptor (ER) and Progesterone receptor (PR)} and HER2 testing is recommended to be done on all primary invasive breast carcinomas and on recurrent or metastatic tumors, and reported as per guidelines published by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP).

Hormone receptor (HR) expression in invasive breast carcinoma has both prognostic and predictive significance; the use of endocrine therapy in HR-positive breast carcinomas has been shown to reduce the rates of recurrence and mortality.

The recommended pre-analytic and analytic variables required for tests, like cold ischemia time, are strictly maintained.

Endometrial Carcinomas – Hormone receptor (ER and PR) expression is also assessed on primary invasive endometrial endometrioid adenocarcinomas to predict response to endocrine therapy.

  • Human epidermal growth factor receptor 2 (HER2) Receptor testing

Breast Carcinoma- HER2 status is primarily evaluated to determine patient eligibility for anti-HER2 therapy in breast carcinomas. Reflex FISH (fluorescence in situ hybridization) test is performed in equivocal cases to confirm the amplification status.

 Female genital tract – HER2 Testing is done on high grade endometrioid and serous endometrial carcinomas as a prognostic marker.

Gastric carcinoma – Assessment for tumor HER2 overexpression using IHC is done to determine patient eligibility for anti-HER2 therapy.

Salivary gland tumors- HER2 expression is done using IHC as a diagnostic marker for the aggressive salivary duct carcinomas.

  • BRAF V600E

IHC for BRAF V600E is done as a surrogate marker for BRAF gene mutations (with predominant mutation seen at V600E). It has a role in thyroid papillary carcinoma, colon adenocarcinoma, and melanoma, with therapeutic implications.

  • Human papillomavirus (HPV)

P16 immunohistochemistry is used as a surrogate marker of active HPV in head and neck oropharyngeal squamous cell carcinomas (OPSCC), and cervical carcinomas.

  • Epstein-Barr virus (EBV) detection using in situ hybridization (ISH) for EBV-encoded small RNAs (EBER) in nasopharyngeal carcinomas, lymphoepithelial carcinomas, and also for several types of hematopoietic malignancies.
    • NUT (nuclear protein in testis) : IHC for NUT is used as a diagnostic marker for NUT midline carcinoma which is a rare, aggressive, squamous cell carcinoma variant uniquely defined by NUT gene translocations.
      • Succinate Dehydrogenase (SDH)
      • IHC marker SDH-B is performed to identify cases with germline/sporadic mutation in the enzyme succinate dehydrogenase, seen in gastrointestinal tumors (GISTs), extra adrenal paragangliomas, pheochromocytomas and some renal tumors (SDH-B deficient RCC).

        • PD-L1 (programmed death ligand-1)

        RGCIRC was the first centre in North India to introduce PD-L1 immunoexpression testing by IHC as a predictive marker of immunotherapy in various solid organ tumors.

        PD-L1 scoring is done by Roches’s Ventana SP263 clone, on Ventana  Benchmark XT autostainer. The SP263 assay is CE (European conformity) labeled to inform treatment decisions in lung cancer patients being considered for Keytruda (Pembrolizumab) immunotherapy as a first line of treatment.

        PDL-1 scoring for by monoclonal antibody SP142 is done on benchmark ultra Ventana autostainer, which is FDA approved assay for metastatic triple negative breast cancer (TNBC), Non-small cell lung carcinoma (NSCLC) and urothelial carcinoma for patient selection, to be treated with Tecentriq (atezolizumab).

        • Mismatch Repair (MMR) Immunohistochemistry Testing

        IHC testing for DNA MMR protein expression (MLH1, MSH2, MSH6, and PMS2 expression) is performed to detect germline mutations in these MMR genes, and identify Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome [HNPCC]) which is associated with risk of cancers of colorectal, endometrial, gastric, upper urinary tract origin.

        HNPCC is an autosomal dominant inherited cancer syndrome with mutation in DNA mismatch repair genes. Loss of one or more proteins by IHC is suggestive of defective DNA mismatch repair within the tumor.

         

Our Locations
  • Sir Chotu Ram Marg, Sector – 5, Rohini Institutional Area, Rohini, New Delhi, Delhi – 110085, India

    +91-11-47022222 | Fax +91 11 27051037

  • Squadron Leader Mahender Kumar Jain Marg, Block K, Niti Bagh, New Delhi, Delhi 110049

    +91-11-45822222 / +91-11-45822200

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