|
Test available.
Update: Dakocytomation’s EGFR PharmDx is FDA approved and indicated as an aid in identifying cancer patients eligible for treatment with Erbitux (cetuximab).
Erbitux is a monoclonal antibody that binds to EGFR resulting in inhibition of tumor cell growth, survival and progression. Erbitux is used to treat metastatic colon cancer with irinotecan or alone in patients who cannot tolerate irinotecan. For further information please see www.ERBITUX.com and/or http://www.dakocytomation.us/.
The epidermal growth factor (EGF) and its receptor, EGFR, have been identified as key drivers in the process of cell growth and replication. Epidermal Growth Factor Receptor is a 170 kD membrane protein which consists of an extracellular EGF-binding domain, short transmembrane region, and an intra-cellular domain with ligand-activated tyrosine kinase activity. EGFR has two common ligands: EGF and Transforming Growth Factor-alpha (TGF-a ). When TGF-alpha binds to EGFR, tryosine kinase of the receptor is activated, followed by phosphorylation and an increase in cytosolic calcium ions within target cells resulting in DNA synthesis and proliferation and differentiation of the cell.
Normal cell growth and proliferation is tightly regulated by the production and activation of growth-promoting and growth-inhibiting factors. This results in differentiated cells growing in a controlled and regulated manner to maintain the normal integrity and functioning of the organ. Malignant tumors are the result of uncontrolled cell proliferation. Increased activity at the EGFR receptor has been implicated in a variety of solid tumors, including colorectal tumors. Over-expression of EGFR is observed in endometrial carcinoma and it is correlated to myometrial invasion. EGFR is commonly expressed in head and neck carcinomas. The expression in breast carcinoma is variable but it is inversely correlated to negative estrogen receptor status of the tumor, and it is also observed frequently with tumor metastasis. In lung neoplasms, the overexpression of EGFR is demonstrated in metaplastic squamous epthelium, squamous cell carcinoma, adenocarcinoma, and neuroendocrine lung tumors. There is a significant correlation between EGFR expression and advanced tumor stage in invasive transitional cell carcinoma of the urinary bladder, glioblastoma multiforme, and variable expression of the receptor is found in pilocytic, low grade or anaplastic astrocytoma.
Excessive activation of EGFR is also known to be associated with advanced stages of cancer and a poor prognosis for the patient.
Veripath OncoDiagnostics offers the FDA approved EGFR PharmDX as a part of the standard colorectal cancer panel, but it can also be ordered individually. Currently, we are using an automated image analysis system to quantitatively score EGFR expression. For more information contact Dr Raheela Ashfaq at the OncoDiagnostic Laboratory at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu
Selected References:
- Goustin AS Leof EB, et al. Cancer Research 46:1015-1029, 1986.
- Aaronson SA. Science 254:1146-1153, 1991.
- CohenS, et al. J Biol Chem 257:1523-1539, 1982.
- Chen WS, et al. Cell 59:33-43, 1989.
- Pusztai L, et al. J Pathol 169:9-14, 1993.
- Niikura H, et al. Human Pathol 27(3):282-289, 1996.
- Rusch V, et al. Ann Thorac Surg 62:798-810, 1996.
- Agosti RM, et al. Virchows Arch Pathol Anat 420:321-324, 1992.
- Christensen ME. Danish Med Bull 45(2):121-124, 1998.
- Neal DE, et al. Lancet 1:366-368, 1985.
- Toi M, et al. Int J Cancer 43:220-225, 1989.
- Salomon DS, et al. Critical Reviews in Oncology/Haematology 19:183-232, 1995.
|
