Supervisors info:
Ανδρέας Χ. Λάζαρης, Καθηγητής Ιατρικής, Ιατρική Σχολή, Εθνικόν και Καποδιστριακόν Πανεπιστήμιον Αθηνών
Summary:
Colorectal cancer is one of the most common neoplasms worldwide. Morbidity and mortality rates vary considerably around the world and the incidents are increasing, especially in developing countries. According to data from Global Cancer Observatory (GCO) of the World Health Organization (WHO), colorectal cancer was the 3rd most frequently diagnosed and the 2nd most deadly cancer in the world in 2018. Differences in incidence are observed between sexes, while the disease is rare before the age of 40 years. The etiological basis of the disease is complicated and not clearly defined. It is characterized by the interaction of environmental, individual and genetic factors in the various stages of carcinogenesis.
The prevention of colorectal cancer, following a time sequence, aims to prevent the onset of the disease, stop its neoplastic growth and prevent the progress of an already established disease. The diagnostic procedure consists of clinical examination, laboratory tests based on the detection of faecal haemoglobin and imaging methods such as, mainly used, colonoscopy. The clinical outcome of the disease and the survival of the patients depend mostly on the histopathological stage of the tumor upon diagnosis. Symptomatic patients, usually suffering from advanced disease with lymph node infiltration and metastatic outbreaks, report a five-year survival rate of approximately 50%. The treatment of colorectal cancer is based on the prognosis and consists of surgical and complementary therapy. Modern therapies, based on the molecular profile of the tumor, use biopharmaceutical targeting agents, looking for a personalized approach.
Colorectal cancer is a predominantly sporadic disease 65%-85% of cases, the familial form is observed in 10%-30% of cases, while the inherited type with the occurrence of genetic syndromes is responsible for less than 5% of all cases. Multistage neoplastic process is based on molecular changes, which impart heterogeneity to the disease, determine its molecular profile and shape the immunophenotype.
Phenotypic determination is performed with the most widespread, widely used, laboratory technique of Immunohistochemistry. Immunohistochemistry is based on the specific binding of antibodies (monoclonal or polyclonal) to intracellular or extracellular antigens, also known as biomarkers, located in situ in the tissue under study. Detection of binding sites is most commonly done using an enzymatic chromogenic reaction. There are both a wide variety and abundance of antigenic molecules that can be used in the immunohistochemical investigation of primary and metastatic colon cancer. These biomarkers are distinguished, based on their role, in diagnostic, prognostic and predictive biomarkers.
Proteins such as keratins CK20 and CK7, which are tested together and in combination with the transcription factor CDX-2, GPA33 with a strong presence in well-differentiated tumors and CDH17 expressed in all metastatic colorectal adenocarcinomas are known for their diagnostic value. MMR proteins are immunohistochemically tested to indicate the presence or absence of Lynch syndrome, while at the same time they are involved in the prognostic stratification of patients with colorectal cancer and their therapeutic response. Antigens such as SMAD4 protein and Villin have prognostic value. Predictors, including amplification of the Her-2 gene and three NTRK gene receptors, are involved in fusion events.
As there is no specific biomarker for colorectal cancer, research is still ongoing. Systemic studies and clinical trials aim to find new reliable protein molecules, to confirm their value in terms of diagnosis, prognosis and treatment, but also to validate the biomarkers already used so far.
Keywords:
colorectal cancer, immunohistochemistry biomarkers, diagnostic, prognostic, predictive
