The holy trinity of cancer care: biochemistry, microbiology and pathology

Cancer originates at the genetic micro-molecular level within a cell — resulting in a cascade of subtle biochemical and cellular abnormalities that escape internal patrol — and eventually manifests as a detectable disease. Onco-biochemistry involves quantifying tumour markers, enzymes, hormones and metabolites in blood and body fluids for diagnosis, prognosis and monitoring treatment response or resistance. Clinical biochemists monitor the chemical signature of cancer and the body’s systemic response to treatment. They determine the baseline biochemical parameters in a cancer patient and any reversal of these chemical signals as a result of cancer treatment. Tumour markers such as prostate specific antigen (PSA), cancer antigen‑125 (CA‑125) and carcinoembryonic antigen (CEA) can flag prostate, ovarian and colon cancers even before symptoms appear. Enzyme tests such as lactate dehydrogenase (LDH) and Beta2M give an idea of the overall cancer burden. Protein electrophoresis, a test that separates blood proteins, can reveal a distinct “M‑spike” that helps diagnose multiple myeloma. Subsequently, the down-trending of these values reveals whether treatment is working, before a radiological scan can capture the changes. Advanced biochemical techniques such as serum-free light chain assays allow the treating oncologist to detect even tiny amounts of remaining cancer cells that could trigger a relapse. Measuring therapeutic drug levels in blood allows precise and safe dosing. Baseline and periodic liver function tests and kidney function blood tests reveal the trend of systemic response. Clinical biochemists are the first to spot cancer related life-threatening complications such as tumour lysis syndrome and hypercalcemia of malignancy. In the high-risk environment of a bone marrow transplant, biochemistry provides the “dashboard” for recovery by monitoring rejection and electrolyte homeostasis. How oncopathology works | Photo Credit: Special Arrangement Microbiologists play a significant role in the management of cancer patients. Approximately 20% of cancers are caused by microbes: viruses and bacteria. Viruses including the human papillomavirus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, Kaposi’s sarcoma-associated herpesvirus andHuman T-lymphotropic Virus-1 all cause cancer. Bacteria such as Helicobacter pylori are associated with stomach cancer. Early detection of these microbes and treatment of the infection caused may help in prevention. Additionally, cancer treatment weakens the immunity of patients and renders them susceptible to life-threatening opportunistic infections. Microbiologists use advanced detection techniques such as BACTALERT 3D/240 (blood microbe culture system), MALDI TOF (matrix‑assisted laser desorption ionisation time‑of‑flight) for rapid and accurate detection of the culprit microbes and to identify the specific antimicrobial agents (drugs) needed to treat the infection. Early detection, therefore, supports rational antibiotic use, de-escalation of antibiotic therapy and antibiotic stewardship. Cumulatively, these advanced microbiological diagnostic techniques prevent the emergence of antimicrobial resistant microbes and impact countless lives. “Is it cancer or not?” That’s what a pathologist, examining biopsies under the microscope, determines. The exact type and grade of cancer, along with molecular information (gene changes and protein markers) that guide targeted drugs and immunotherapy, can all be found. Traditionally, pathologists have been able to diagnose diseases by studying the gross abnormalities seen in the diseased organs followed by structured sampling of the organ under the microscope with up to 1,000 times amplification. The molecular revolution has led to a paradigm shift in the way pathology related to the diagnosis of cancer is practised. Modern cancer pathologists (oncopathologists) are able to detect root cause changes at the molecular level. They not only confirm the diagnosis of cancer but also provide highly accurate characterisation of the type of cancer based on cytology, histomorphology, karyotyping, immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH), polymerase chain reaction and next generation sequencing. Oncopathologists provide a comprehensive final diagnosis of cancer by integrating the morpho-molecular subtype and grade of cancer with its stage, by clinico-radiological correlation. Molecular profiling of cancers has become the cornerstone for the practice of personalised cancer medicine. With the emergence, and subsequent drop in costs of cutting-edge technologies such as whole genome sequencing, and the availability of AI tools to analyse the huge amounts of data generated, oncopathologists can diagnose and predict the emergence of human cancers from their inception through various stages of development and spread. Oncopathologists also play a major role in cancer screening and prevention through identification of precancerous lesions in Pap smears, endometrial biopsies of the uterus, colon polyps and the study of other precancerous oral and skin lesions. They provide real-time, intraoperative consultations (termed ‘frozen section’) to operating surgeon and guide the surgical boundaries of tumour excision to ensure complete tumour removal. The emergence and availability of various biomarkers have helped oncopathologists guide precision treatment. They play a pivotal role in monitoring the response of a patient to cancer treatment too. Not only do they diagnose minimal residual disease and help confirm remission, they also enable treating clinicians to plan further treatment type and duration by detecting early relapse (recurrence) of cancer, while also helping detect the emergence of drug resistance mechanisms and suggesting alternative treatment strategies. Biochemistry, microbiology and pathology are the eyes that see the unseen world of cancer care. They quietly do the heavy lifting behind the scenes, from early detection, safe personalised treatment, to monitoring of long‑term survival and hope. (Dr. Shirley Sundersingh is head, department of oncopathology, Cancer Institute (WIA) drshirleysundersingh@gmail.com; Dr. Thuthi Mohan is head, department of clinical biochemistry Cancer Institute (WIA) drthuthimohan@cancerinstitutewia.org; Dr R. Packia Nancy is head, department of microbiology, Cancer Institute (WIA) p.nancy@cancerinstitutewia.org)