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Two sides of the same coin: Liquid Biopsy vs Tissue Biopsy

Keerthi Ranganathan

Scientific Content Developer
4baseCare

A biopsy is a method to take a piece of tissue, cells or the tumor-driven components of the blood from the body for testing in a laboratory to find the type of cancer. Biopsies are the only way for the diagnosis of most of the cancer by closer examination of cells or tissues. Imaging tests like CT scans or MRIs, are helpful in detecting irregular masses of tissue, but they alone cannot be able to differentiate between cancerous cells and non-cancerous cells. Tissue and liquid biopsies are the two sides of the same coin as both are the diagnostic tools, used in the diagnosis of cancer.

Tissue biopsy

Clinically, tissue biopsies are the most frequently used classical method for molecular analysis in cancer diagnostics. It is an invasive technique to extract a sample from cells or tissues for examination to determine the presence and type of cancer. Anesthesia is given to the patients for tissue biopsy to remove discomfort during the procedure of sampling. There are various types of tissue biopsies available, like needle biopsy, endoscopic biopsy, skin biopsy, surgical biopsy and bone marrow biopsy.

    1. Needle biopsy

Needle biopsy is also called percutaneous biopsy and it is used to take samples from breast lumps and enlarged lymph nodes which the care provider feels from above the skin. When combined with an imagine test, it is used to take samples from the area that cannot be felt from above the skin.

    1. Endoscopic biopsy

Endoscopy biopsy is also a type of tissue biopsy in which a sample is collected by inserting a long, thin and flexible tube with light at the end that carries special tools to take tissue or cell samples from desired part of the body, like bronchoscopy (lungs), colonoscopy (colon) and cystoscopy (bladder). This procedure will be conducted under anesthesia.

    1. Skin biopsy

Skin biopsy is used to take samples from the skin and is helpful in diagnosis of melanoma and other cancers by knowing the condition of the skin. In this procedure, local anesthesia is given to the patients.

    1. Bone marrow biopsy

A bone marrow biopsy is generally used to diagnose a variety of blood related issues, both cancerous and non-cancerous. It can diagnose leukemia, lymphoma and multiple myeloma related to blood. It can also detect types of cancers which started somewhere else and moved to the bone marrow. In this biopsy, a sample is drawn from the bone marrow out of the back of your hipbone with a long needle under the effect of local anesthetic.

    1. Surgical biopsy

Surgical biopsy is recommended by a doctor when the sample cannot be taken out by any other type of tissue biopsy. In this, removal of a breast lump or lymph node is done by a doctor through surgery for diagnosis of cancer. Surgical biopsy is sometimes used to remove all suspicious cells. It also requires local anesthesia.

Limitations of tissue biopsy

  1. Invasive techniques require anesthesia. Sometimes a hospital stay is also in need of a tissue biopsy.

  2. Yields inadequate DNA material for genetic analysis at a significant rate.

  3. Intra-tumor heterogeneity cannot be detected by tissue biopsies because it is unable to capture the tumor’s mutational status.

  4. Frequent monitoring for the development of new mutations or genetic modifications due to which resistance is developed is not possible with tissue biopsy because it is an invasive method.

  5. Repeated sampling over time is generally not practicable for routine monitoring of the drug therapy and patient’s response.

  6. Sometimes, the condition of the patient and location of the tumor may hamper the sampling by tissue biopsy.

  7. Tissue biopsies are also associated with adverse effects like risks of tumor dissemination, infections and bleeding due to invasion.

All these issues are overcome by using liquid biopsies. Liquid biopsy is used as a complementary or alternative to classic tissue biopsy for the diagnosis of cancer.

Liquid biopsy

Liquid biopsy is a less invasive technique, also known as fluid biopsy or fluid phase biopsy. It is done by taking bodily fluids like blood, urine, cerebrospinal fluids and stool samples from the patient for diagnosis of cancer. The utility of liquid biopsy tests in cancer diagnostics provides potential and beneficial outcomes and turns the focus of cancer management towards it.

Liquid biopsies could provide a potential revolution in the field of cancer diagnosis and treatment. Analysis with it for the diagnosis of cancer has been based on analytes of the biological fluid. The analytes which are released by tumors in bodily fluids are circulating tumor cells (CTCs), circulating nucleic acids (circulating tumour DNA (ctDNA), the tumour-derived fraction of cell-free DNA (cfDNA) in the plasma and cell-free RNAs (mRNAs, long non-coding RNAs and microRNAs), extracellular vesicles, tumour-educated platelets, proteins and metabolites.

While liquid biopsies have some merits and limitations too.

Merits of liquid biopsy

  1. Samples can be more easily obtainable throughout the management of the disease. Hence, it can be easily repeated because of its less invasive nature and helpful for monitoring patients’ responses to therapy during and after treatment to promote personalized medicine concepts.

  2. Liquid biopsy provides information of changes at the molecular level of the cancer during and after treatment and hence, it could be a potential tracker for the identification of the causes of the development of drug resistance.

  3. It can be used to monitor the progression of cancer and act as a monitoring method for cancer patients who have completed treatment but are at high risk of recurrence of disease.

  4. Liquid biopsy analysis in cancer management starts with the identification of patients with tumor disease to monitoring of treatment and testing for cancer recurrence.

Limitations of liquid biopsy

  1. Compared to tissue biopsies, the amount of tumor-derived analytes in liquid biopsy samples is very small, diluted by material from normal cells present naturally in body fluids. This poses a challenge in the application of liquid biopsy for detection or screening of cancer with low tumor burden. Hence, a small number of biomarkers may reduce the sensitivity of detecting cancer using a liquid biopsy sample.

  2. Many tumor derived analytes or biomarkers are not specific to any particular type of tumor or cancer, making the diagnosis of them problematic. The one example to address this issue is that high serum levels of prostate specific antigen are usually associated with prostate cancer but it may also increase in non-malignant prostate disorders.

  3. Compared to tissue biopsy, which is well established, standardization of both pre-analytical (blood collection tube specifications, time and procedure to obtain plasma from the blood and procedure for the isolation of biomarkers of liquid biopsy from plasma) and analytical procedures (focusing on maximization of yield of biomarkers from the plasma) of liquid biopsies are required for generalized all liquid biopsies analytes.

References

  1. Esagian SM et al. 2020. Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review. Journal of cancer research and clinical oncology, 146(8), 2051–2066.

  2. Andersson D et al.2020. A Liquid biopsy analysis in cancer diagnostics. Mol Aspects Med. 72:100839.

  3. Poulet G et al. 2019. Liquid Biopsy: General Concepts. Acta Cytol. 63(6):449-455.

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