Oncology #1 : "Liquid Biopsy" in cancer diagnosis. What are the current available tumour markers ? Part 1
Hey guys. It's been awhile since I last posted. As a muslim, I celebrate Eid every year and the festival is pretty much around the corner so I have less time to concentrate on blogging but I'll make it up for sure !
So I’ve read an article written by Rory Smith of the CNN recently which sparked my interest to write this article. You can read more about the article in the reference list at the end of this blogpost. I've decided to come up with something that is related to cancer because recently a family friend of mine just passed away due to stage 4 cervical cancer. She was told to be free from cancer a year ago but then a lot of symptoms came and she became terminally ill. Finally she fell into this ferocious disease and was only provided palliative care to make her feel very comfortable. Quite a sad incident because she helped our family during our bad days as she was my mom's boss at her workplace before this. Can't believe that I have the opportunity to actually visit her in the Gynae-Onco ward. Perks of being a medical student eh.
Alright back to the topic. Fiona Osgun of the Cancer Research UK stated that
Detecting cancer early, before it has spread is one of the most powerful ways to ensure more people are offered treatments which give them a better chance of beating the disease
Yeah, it is indeed a well-known fact that Stage IV cancers tend to have poor prognosis. As in those people at the terminal-stage malignancy generally are told to have a certain amount of time left to live in this world. The clock starts ticking when the diagnosis was made. Some types of cancers at the latter stage are incurable and those people are only treated with palliative care, which means they are given supportive management just so that they can have good quality of life. Similar to my mom's boss. This is to ensure that they are free from debilitating symptoms such as pain.
The article further stated that there are new and blooming researches which study on cancer detection via just a mere blood test. Usually, a tissue biopsy is the gold standard in determination on whether the organ is already cancerous or not. The procedure is indeed invasive as you need to puncture the patient to reach the deep seated organ. Some other radio-imaging tests such as CT scan can actually delineate the cancer’s whereabouts. However, bear in mind that CT scan or Computed Tomography Scan does pose a risk in stimulating cancerous growth on the scanned part as CT generates radiation. Moreover, some dye or contrast is injected in contrast-based CT scan. Some people are allergic to some types of contrast and it is a well known fact that contrasts can injure the kidneys.
Cancer UK further explained that
For many common cancers, rates of survival triple when diagnosed at an early stage
Hence, it is of the upmost importance for physicians to diagnose malignancies earlier, preferably at the beginning of the insidious transformation of the cells which is known as metaplasia stage.
Tumour marker, which is a term that is used to describe a biological marker that is present or has elevated values than the normal range. They are commonly found in body fluids in our body such as blood. Oncology on the other hand, is a branch or field of medicine that sort of deals with malignancies. Physicians who specialize in Oncology have to deal with the diagnosis, prevention and treatment of cancer. The origin of the word onco or onkos is in Greek, which means tumour or mass.
There are all sorts of kind of tumour markers which can be detected via just a simple blood test. However, the sensitivity and specificity of each tumour markers vary among each other. Some tumour markers are very specific to a type of cancer but they can’t be detected in all cancer cases. There are also some tumour markers which are not very specific to a certain type of cancer but they can be present when the patient has any sort of cancer. This poses quite a challenge to the medical field but hey, it is better than nothing right?
Tumour markers have many great use especially in the oncological field. They can be used as a screening method, especially when the target group is huge. You can’t expect the hospital to run CT scans or liver biopsies to every single patient that comes to the clinic. However it is not a realistic plan to run this blood test to everyone either, so only targeted people should be checked for their tumour markers level.
AFP
Alpha fetoprotein or AFP is one of the famous tumour marker used especially in detecting or screening for hepatocellular carcinoma. HCC or hepatocellular carcinoma is one of the commonest primary cancer of the liver, as in HCC arises originally from the liver itself. Take note that the most common cancer in the liver is due to secondary metastasis, as in this cancer are brought via the blood stream or any other routes from a different organ.
HCC develops in the setting of chronic liver disease, which is often associated with chronic hepatitis B or hepatitis C infections. Apart from that, alcoholism is one of the risk factor of hepatocellular carcinoma. AFP is a major protein that is produced in the yolk sac during the fetal period when we are still in our mom’s tummy. As a protein, AFP binds to all sorts of substances such as copper, nickel, bilirubin and fatty acids. Structure-wise, AFP is a glycoprotein that is made up of 159 amino acids. Amino acids are the smaller forms of protein.
Functionally, AFP is not known to have any significant job in our body. AFP level is elevated in HCC and germ cell tumours. At levels of more than 200, AFP has a sensitivity of 31% and specificity of 99%. Which means among 100 cases of HCC, 31 patients will show elevated AFP level and if there’s 100 individuals with elevated HCC, 99% of them have HCC. Thus, it is not that specific but it is highly sensitive.
CA 15-3
CA 15-3, is the abbreviation of Carcinoma Antigen 15-3. It has a big role in the management of breast cancers. Breast cancer is the most common cancer among women which affect almost 12% of women, worldwide. I have recently attended a class on common breast diseases and my lecturer is one of the renowned breast surgeon in Malaysia. She provided us many information in the surgical management of this type of malignancy. About 1% of breast cancer patients are male. So don’t be surprise if you heard anyone with Adam’s apple with this sort of cancer as they are not just confined to woman only. About 5% of cancer patients have a genetic influence in it, as in probably they have a first degree relative with breast cancer. However, 95% of breast cancers occur sporadically which means the victims do not have any family members diagnosed with the disease. It happens spontaneously.
CA 15-3 is derived from the MUC1 gene and it is associated with CA 27-19. According to uptodate, these biochemical markers of breast malignancy are elevated alongside with advancing primary disease and reflects the body’s total burden of the malignancy. Hence, instead of the screening process of breast cancer, they are used to monitor treatment response. This means that the level of this tumour marker can decline if the patient is properly treated.
CA 19-9
Carbohydrate Antigen 19-9 is first discovered in victims of pancreatic cancer and colon cancer back in 1981. In people with mass arises from the pancreas, CA 19-9 can be a great tool in distinguishing pancreatic malignancies from other diseases of the pancreas. However they are not recommended to be used in screening of pancreatic cancer as they have poor sensitivity and specificity to the disease. The other cons of CA 19-9 is that, the level of this tumour marker can be elevated in other types of cancers such as colorectal cancer, oesophageal cancer, and even in HCC. Hence, it is a poor decision to rely on CA 19-9 in diagnosing pancreatic cancer.
CA-125
Carbohydrate Antigen 125 is one of the greatest discovery in the world of oncology medicine when it comes to cancer screening. The protein was founded by Robert Bast and his research team back in 1981. The number 125 was coined from the research as CA-125 was the 125th antibody produced by the ovarian cancer cell line.
The famous American Congress of Obstetricians and Gynecologists recommended that women with moderate risk of ovarian cancer such as smoking status and family history of ovarian cancers should be screened via the detection of CA-125 in the blood.
Similar to some other tumour markers, CA-125 is not specific to only ovarian cancer. Other cancers those can cause elevation in CA-125 level includes endometrial cancer, lung cancer, breast cancer and even malignancies at the gastro-intestinal tract.
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Apart from the screening process, CA-125 shows benefits when it comes to monitoring the treatment response. Normal values of CA-125 is approximately around 0-35 (U/mL). After receiving cancer treatment, the blood level of CA-125 can be monitored back to check whether the treatment has showed benefits or not.
Lastly, in the presence of adnexal mass or pelvic mass upon physical examination, CA-125 can aid clinicians to differentiate whether the mass is benign or malignant. If the value of CA-125 is more than 65 U/mL, the mass is very likely to be malignant in origin. Benign masses are non-cancerous usually.
Ovarian cancer has more cases in the developed country in comparison to the developing countries. In the year 2014, new cases in the developed country was about 9.4 per 100, 000 in comparison with 5.0 in the developing countries. This shows that environmental factors and excess food consumption play a big part in the carcinogenesis.
I will be covering on other tumour markers on my upcoming post as there are many of them. According to Dr. Nickolas Papadopoulos,
The ability to diagnose cancer early on and then offer patients effective treatment for their disease will likely save many lives
This is very true as when the cancer spreads to adjacent structures or in worst case scenario, to other far and vital organs such as the brain or the liver, it is considered as "too late". Early diagnosis and intervention makes the vicious disease very curable. Some types of cancers can only cause symptoms in late stages, making it highly unlikely to be treated in the initial phase of the cancer progress. Hence, new innovations in the world of oncology such as the "liquid biopsy" are pretty much welcomed and those with high risk of developing malignancy such as strong family history of certain types of cancer should be screened via these new inventions. Thanks for reading :)
References
- Smith R. Blood test offers hope of finding cancers before symptoms develop. Health. CNN. Retrieved on June 11, 2018 from https://edition.cnn.com/2018/06/01/health/blood-test-cancer-screening-intl/index.html
- Clinical features and diagnosis of primary hepatocellular carcinoma. Uptodate. Retrieved on June 11, 2018 from https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-primary-hepatocellular-carcinoma
- Tumour Marker. Wikipedia. Retrieved on June 11, 2018 from https://en.wikipedia.org/wiki/Tumor_marker
- Ovarian Cancer. Wikipedia. Retrieved on June 11, 2018 from https://en.wikipedia.org/wiki/Ovarian_cancer#Risk_factors
- CA 15-3. Wikipedia. Retrieved on June 11, 2018 from https://en.wikipedia.org/wiki/CA_15-3
- Tumor markers. Cancertreatmentcentersofamerica. Retrieved on June 11, 2018 from https://www.cancercenter.com/treatments/tumor-markers/