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Discovered in 1981 Cancer Antigen 125 is a mucin also known as MUC16 which is a high molecular weight glycoprotein expressed in epithelial cell types. CA-125 is derived from Mullerlian and Coelomic epithelium that includes the endocervical, endometrial, tubal, peritoneum, and pericardium epithelia. The normal function of mucins is to aid in the production of mucus that covers the epithelium.(7) The mucus provides lubrication for the movement of objects, provides a barrier to pathogens and acts as a permeable viscous layer that allows for the exchange of nutrients and gasses with the epithelium.(8) Over 80% of patients with ovarian cancer express CA-125 with levels that correlates with the histology, and stage of disease at presentation.(9) The raise in serum concentration of CA-125 is due to vascular invasion, destruction and inflammation of tissue associated with malignant disease.(9) There are many applications for analysing CA-125 in the laboratory and typically the normal range for CA-125 is 0 - 35 U/mL.(10) As 80% of patients express CA-125 at presentation there has been vast amount of research that is still on going to analyse the prognostic value of CA-125.
Prognostic Factors for Ovarian Cancer:
Prognostics factors are defined as phenotypes that correlate with the overall survival of a patient. The general prognostic factors for ovarian cancer age, the histological grade of the tumour, volume of ascites, the stage of the disease, and the patients' ability to cope with the morbidity of the effects caused by the tumour and treatment. These prognostic factors can help a clinician to devise a treatment strategy that is relatively individually tailored for the patient. Treatments could involve the use of cytotoxic drugs or a combination of cytotoxic drugs and debulking surgery depending on the disease state. As a means of research prognostic factors help to identify patients with particularly poor prognostic outcomes and highlight the need for alternative treatment strategies. Therefore the use of a biomarker could aid the patients' survival rate with the selection of the correct treatment strategy. An example of using a biomarker as a prognostic marker to tailor therapy (that is associated with a favourable or poor outcome) is metastatic breast cancer and the use of Her2 receptor positive status.(11) Her2 has led to the development of anti-Her2 therapy through the use of Herceptin which is a monoclonal antibody targeting the Her2 receptor .(11)
Is CA-125 a good prognostic marker for Ovarian Cancer?
CA-125 levels can be raised in many benign conditions such as endometriosis, pelvic inflammatory disease, ovarian cysts, uterine fibroids and menstruation. CA-125 levels can also be raised in other forms of adenocarcinomas such lung, breast, endometrium, and pancreas.(2) For this reason CA-125 is not an adequate prognostic biomarker on its own and such disease states should be excluded if intending to monitor raised CA-125 levels. However CA-125 levels at presentation along with the other prognostic factors such as age, grade and stage can provide prognostic value. Once ovarian cancer has been diagnosed the CA-125 analysis can provide prognostic value when used to guide and monitor treatment. For instance when a patient presents with a stage I epithelial ovarian cancer (EOC) with a serum concentration of less than 65 U/mL (considered to have a better prognosis) a less extensive bulk reduction surgery can be offered than patients presenting with CA-125 levels greater than 65 U/mL (considered a worst prognosis).(2) Furthermore CA-125 concentration can play a vital role when used to monitor the patients' response to chemotherapy. When a patient has CA-125 levels greater than 65 U/mL at the start of chemotherapy Rustin et al suggests that after two samples a reduction of 50% from the baseline CA-125 level indicates an anti tumour response (good prognosis) as long as there is no other indications of tumour progression.(12) Equally it is noted that a rising serum concentration of CA-125 can be suggestive of a failure of a therapy. If the patients CA-125 levels continue to rise in the presence of therapy it is reasonable to question the value of continuing the therapy. The monitoring of CA-125 levels is also useful when monitoring for the persistence of the disease after completion of chemotherapy. If after 6 cycles of chemotherapy CA-125 remains raised there is a higher than 90% chance that residual disease is present.(9) However a single raised result in the absence of symptoms or physical mass should not be accepted as recurrence of disease and other factors such as menstruation, ascites and liver function should be taken in to account and a second sample analysed. Conversely a normal CA-125 result upon completion of chemotherapy does not rule out the recurrence of disease as it is reported that 50% of EOC patients that have normal CA-125 levels in fact have microscopic disease at second look surgery.(13)
The initial CA-125 level and the subsequent decline after initiation of chemotherapy has been suggested as an important prognostic indicator in EOC although specificity of results need to be considered in the absence or presence of other clinical presentations.
Is the future screening?
At this moment in time there is not screening program being implemented in the UK but patients deemed high risk (2 or more relatives on the same side of the family have been diagnosed with ovarian cancer or have family members with a known genetic fault such as BRCA1 or BRCA2)(14) can take part in the UK Familial Ovarian Cancer Screening Study (UK FOCSS) after consultation with their GP. As mentioned in this essay the patients' prognosis dramatically declines the later the stage of disease at presentation