| Alpha - fetoprotein (AFP) is a tumor associated
embryonal antigen produced by fetal liver,
hepatocellular carcinoma, yolk sac tumors, and
germ cell tumors of testicular and ovarian origin.
Embryonal carcinoma and endodermal sinus
tumors stain positive for AFP. |
| BCL2 - This antibody detects t (14; 18) and can be
used to distinguish neoplastic germinal centers from
reactive ones. |
BCR-ABL by PCR - The hallmark genetic abnormality of CML is a t (9;22)(q34;q11) translocation, which was first discovered as an abnormal, small chromosome, named the 'Philadelphia chromosome'. This translocation generates the BCR - ABL fusion gene. Tyrosine-kinase activity of ABL is essential for BCR-ABL-mediated transformation, made it an attractive target for therapeutic intervention. Imatinib: selectively induce apoptosis of BCR-ABL+ cells, and is remarkably successful in treating patients with CML. COMPLETE CYTOGENETIC RESPONSE in more than 80% patients. However, obstacles to imatinib-based therapies are:
· persistence of BCR-ABL -positive cells, known as 'residual disease', and is detected by a sensitive nested RT-PCR assay
· due to the emergence of resistance to imatinib (point mutations in the BCR-ABL gene that impair the drug binding) Therefore BCR-ABL molecular based test as most powerful tool for defining genetic lesions.
Triesta offers:
» BCR-ABL qualitative test by PCR
» BCR-ABL quantitative test by PCR |
| |
| Ca125 - This marker is associated with ovarian
epithelial malignancies and is useful in tracing the
origin of adenocarcinoma with unknown primary. |
| Calcitonin - a hormone formed by the C cells of the
thyroid gland. Calcitonin secretion is associated
with medullary carcinomas of thyroid, breast, and
lung. In addition, it helps in identification of C-cell
hyperplasia.Methodology: Immunohistochemistry |
| Calretinin - A 31.5kDa calcium binding protein is
expressed in neural tissues. Calretinin is approved
as a highly sensitive and specific marker for
mesothelial cells and one of the best positive
ma r k e r s f o r di f f e r ent i a t ing ma l i gnant
mesotheliomas from carcinomas. |
| CD3 - It is useful for identification of T-cell lineage of
lymphoid cells. |
CD5 - It is expressed in normal, malignant T-cells
and chronic lymphocytic leukemia cells.
CD10 - is expressed in lymphoblastic, Burkitt's and
follicular germinal center lymphomas |
| Cd15 - It is expressed by some R-S cells in Hodgkin's
lymphoma, granulocytes, and monocytes. |
| Cd20 - It is useful for identification of B-cell lineage
of lymphoid cells. |
| Cd23 - CD23 expression is detected in neoplastic
cells from B-cell CLL |
| Cd30 - It is expressed by R-S cells in Hodgkin's
lymphoma, angioimmunoblastic T-cell lymphomas. |
| Cd34 - Stains positive in vascular and lymphatic
tumors |
| CD43 - It is a pan T cell marker. Aids in diagnosis of granulocytic sarcoma, classifying T cell and low grade B cell lymphoma subtype, differentiating pulmonary MALT lymphoma(CD20 + CD 43+) from lymphoid hyperplasia(CD43neg). |
CD 56 (NCAM) - It is expressed in neurons astrocytes, Schwann cells, NK cells, subset of
T – cells and Neuroendocrine tissues. Tumors that are CD56 positive are myeloma, myeloid leukemia, neuroendocrine tumors, Wilms’ tumor adult neuroblastoma, NK/T cell lymphomas, pancreatic acinar cell carcinoma, pheochromocytoma and small cell lung carcinoma (Ewing’s sarcoma/PNET is CD56 negative). |
| Cd68 - marker for tissue macrophages and blood
monocytes |
| Cd79a - is expressed exclusively on B-cells and B-cell
neoplasms. It is helpful in neoplasms where CD20
expression is aberrantly lost, like after CD20
antibody therapy. |
Cd117 / C-kit - This marker is useful in identification
of gastrointestinal stromal tumors, mast cell tumors
and tumors of myeloid lineage. In addition, C-kit
detection has important therapeutic implications,
like Gleevac in Chronic myeloid leukemia and
gastrointestinal stromal tumor (GIST). |
| CDX-2 is gene that encodes an intestine-specific
transcription factor that is expressed early in
intestinal development and may be involved in the
regulation of proliferation and differentiation of
intestinal epithelial cells. It is expressed in primary
and metastatic colorectal carcinomas and has been
demonstrated in the intestinal metaplasia of the
stomach and intestinal-type gastric cancer. |
Chromogranin A is present in neuroendocrine cells
throughout the body, including the neuroendocrine
cells of the large and small intestine, adrenal
medulla and pancreatic islets. It is an excellent
marker for carcinoid tumors, pheochromocytomas,
paragangliomas, and other neuroendocrine tumors. |
Cyclin D1 As key regulators of the cell cycle, the
Cyclin's control the transition from G1 to S- phase of
cell cycle. Induction of Cyclin D1 shortens the cell
cycle. Over-expression of CyclinD1 is seen in Breast
carcinoma, Mantle cell lymphoma, Laryngeal
epithelial lesions, Bladder urothelial tumors and
Gastric carcinoma, Lung Cancer |
| Cytokeratin7 is used to differentiate between tissues
such as ovarian carcinoma and transitional
carcinoma, which are CK-7 positive, and carcinomas
of gastrointestinal tract and prostate cancer, which
are CK-7 negative. |
| Cytokeratin20- It is expressed in adenocarcinomas
of the colon, transitional-cell carcinoma of bladder
and Merkel-cell carcinomas. It does not stain breast,
lung, and endometrial adenocarcinomas |
| Desmin Is an intermediate filament forming part of
cytoskeleton. It is a useful marker to identify
sarcomas derived from smooth and striated
muscles. |
DNA ploidy and S-Phase analysis - The clinical behaviors of various carcinomas are highly variable without reliable predictive biomarkers. Flow cytometric DNA analysis may provide valuable prognostic information in these tumors. DNA ploidy and S-phase fraction (SPF) measured by DNA flow cytometry have been previously shown to correlate with several clinicopathological variables in several types of tumors indicate that these measurements may clinically useful as independent prognostic factors.
Triesta offers using fresh frozen or FFPE tissue:
» DNA ploidy
» S- phase analysis |
| Estrogen Receptors (ER) & Progesterone receptor
(PR) Estrogen Receptor (ER) expression status in
breast carcinoma is an important prognostic and
predictive biomarker. About 30-40% of tumors are
ER positive, and this is associated with amore
favorable prognosis than ER negative tumors.
Estrogen and progesterone receptor positivity is
associated with a 70% response rate to hormonal
therapy. In contrast, the response rate is <10% among
patients whose tumors are negative for the above
two hormone receptors. |
EGFR Mutation - Epidermal growth factor receptor (EGFR) controls signaling pathways involved in cell differentiation, proliferation and angiogenesis which is one of the most promising targeted therapies in colorectal/lung cancer. Recent study shows, few patients carry somatic mutation in EGFR and these correlate with responsiveness to tyrosine kinase inhibitors, e.g: gefitinib, erlotinib. For non-small cell lung cancer (NSCLC), KRAS mutations reportedly behave as a resistance marker & EGFR as a responsive marker.
Triesta offers:
» EGFR mutation by sensitive ARMS PCR
» EGFR by IHC |
EGFR - Epidermal growth factor receptor (EGFR) controls signaling pathways involved in cell differentiation, proliferation and angiogenesis. One of the most promising targeted therapies in colorectal/lung cancer. Recent study shows some carry somatic mutation in EGFR and these correlate with responsiveness to tyrosine kinase inhibitors, e.g.: gefitinib, erlotinib. For non-small cell lung cancer (NSCLC), KRAS mutations reportedly behave as a resistance marker & EGFR as a responsive mark.
At Triesta we detect:
1: Over expression of EGFR by IHC
2: Gene amplification by FISH.
3: Gene mutation of exon 19 and 20 by ARMS PCR
Triesta offers:
» Over expression of EGFR by IHC
» Gene amplification by FISH.
» Gene mutation of exon 19 and 20 by ARMS PCR |
| FACTORV III It is the best available
immunohistochemical marker for identification of
endothelial cells. Also can be used for identification
of vascular invasion by neoplasms. |
| HER2 (Human Epidermal growth factor Receptor
2) C-erb-2 oncoprotein is the product of the HER2
(neu) oncogene, which is over expressed in 15-30%
of cases of breast carcinoma and has been
demonstrated to be a bad prognostic indicator. |
| HER2 gene is amplified in 25-30 percent of primary
breast cancer. This gene amplification is associated
with disease that is more aggressive. |
| HMB-45 identifies melanocyte differentiation
antigen gp100. It is helpful in identifying tumors of
melanocytic origin especially metastatic amelanotic
melanoma, spindle cell melanoma |
Her2/Neu - Her-2/neu overexpression/ gene amplification is associated with worst prognosis, high recurrence rate and high mortality. Her-2/neu gene is amplified in 18-20% (app) of breast cancers. Her-2/neu positivity reveal relative resistance to hormonal therapy, but Herceptin a monoclonal antibody to Her-2 receptor is effective, especially in metastatic breast cancer management. Herceptin is proved to reduce the risk of recurrence and mortality. Her2 neu can be detected by IHC (protein) and FISH (gene amplification).
Triesta offers:
» Her2 neu by FISH
» Her2 neu by IHC |
| Ki-67 - It is expressed predominantly in S and G2
phases of cell cycle and is therefore a useful marker
for determining rates of cell proliferation. High
proliferation associated with with poor prognosis
and reduced progression free and overall survival. |
| KAPPA & Lambda Light chain - Clonal nature of
immunoglobulin producing cell population can be
determined by the light chain it produces. It is useful
in differentiating plasmacytoma from reactive
plasmacytosis and lymphomas from atypical
reactive hyperplasias and undifferentiated
carcinomas |
K-ras Mutation
Mutation in K-RAS oncogene are frequently found in human cancer such as CRC, Pancreatic, lung, gall bladder, bile duct and thyroid cancer. Therefore mutation can predict prognosis and drug response. Recent studies in non small cell lung cancer and colorectal cancer show that activating mutations of the gene encoding the signaling molecule KRAS, are likely to give rise to resistance to:
• small molecule drugs e.g. (erlotinib; gefitinib)
• Monoclonal antibody treatments e.g. (cetuximab, panitumumab) targeted at the (EGFR)
Triesta offers:
» Kras mutation by sensitive ARMS PCR |
| Leukocyte common antigen (LCA/CD45) is helpful
in determining leukocytic nature of anaplastic
tumors. |
| MYF-4 – Myogenin is a member of a family of
myogenic regulatory genes. These genes encode a
set of transcription factors, which are essential for
skeletal muscle development. It is more specific than
desmin and more sensitive than myoglobin in
detection of rhabdomyosarcomas |
MGMT methylation - Alterations of the pattern of DNA methylation are an early event in cancer and continue through the evolution of cancer. DNA repair enzyme MGMT efficiently removes methyl adducts at the O-6-position of guanine, one of the most prominent and biologically important targets of alkylating agents. Epigenetic silencing of MGMT gene by promoter methylation has been associated with longer overall survival in patients receiving temozolomide. At Triesta, the method to check the promoter methylations status is standardized by Methylation specific PCR (MSP).
Qualitative analysis for DNA promoter methylations for known and novel genes can be carried out.
Triesta offers:
» MGMT methylations by Methylation specific PCR |
MSI (Microsatellite Instability) - Micro satellites – short tandem mono, di, tri or tetra nucleotide, repeat sequences distributed through out the genome. Microsatellite instability (MSI) in tumors means deficiency of DNA mismatch repair due to loss of DNA MMR proteins. MSI was first identified in colorectal cancer, later in HNPCC syndrome, stomach cancer, endometrial and ovarian cancer.
Tumors with MSI-h impart favorable prognosis in colorectal, gastric, pancreatic, and esophageal cancers but are resistant to chemotherapeutic agents. Indications for MSI testing-
· colorectal cancer before 50 yrs,
· HNPCC-related tumors (stomach, bowel, endometrial, ovarian),
· first-degree relatives of HNPCC syndrome
IHC in combination with MSI testing improves the clinical relevance of germ line results from DNA analysis.
Triesta offers:
» MSI testing by PCR |
| NSE (neuron-specific enolase) - Neuron-specific
enolase (NSE) is a glycolytic enzyme that has been
detected in elevated concentrations in certain
tumors like neuroblastoma, small cell lung cancer,
medullary thyroid cancer, carcinoid tumors,
endocrine tumors of the pancreas, and melanoma. |
| Pan Cytokeratins (CK) are intermediate filament
keratins found in epithelial tissue. Monoclonal anticytokeratins
are specific markers of epithelial cell
differentiation. Have been widely used as tools in
discrimination of carcinomas and non-epithelial
tumors such as sarcomas, lymphomas and neural
tumors. In addition, it is useful in detecting micro
metastases in lymph nodes, bone marrow, and other
tissues and for determining the origin of poorly differentiated tumors. |
PML-RARA - Despite rarity Acute promyelocytic-leukemia (APL) represents 10% of AML. Hall mark of APL is PML/RARa translocation (t15,17). In general diagnosis is based upon morphology, Cytogenetics or molecular detection. Incorrectly diagnosed APL with clinical and morphologic criteria can lead to unresponsiveness to ATRA. Also may increase the risk for intravascular coagulation, which can be more severe during chemo. Therefore PML/RARa monitoring through sensitive like RT-PCR is very imp for Identification, treatment and follow-up and risk of relapse.
Triesta offers:
» PML-RARa qualitative test by PCR |
| Synaptophysin - It is a useful marker in
identification of neuronal and neuroendocrine
neoplasms originating from bronchial wall,
pancreas, gastrointestinal tract, thyroid, and adrenal
medulla |
| S-100 protein has been found in normal
melanocytes, Langerhans cells, histiocytes,
chondrocytes, lipocytes, skeletal and cardiac
muscle, Schwann cells, epithelial and myoepithelial
cells of the breast, salivary and sweat glands, in
addition to glial cells. Neoplasms derived from these
cells also express S-100 protein to varying degrees. |
| SMA - It is a cytoskeletal protein and identifies
smooth muscle cells, myoepithelial cells, and tumors
originating from these cells. |
| Thyroglobulin – Positive thyroglobulin stain
indicates tumor of thyroidal origin. |
| TTF-1 a transcription factor binds and activates the
promoter of thyroid and lung specific genes. It is a
selective marker for adenocarcinomas of lung and
thyroid. |
