Dra. Lígia Prado e Castro

Medical Director
of Pathological Anatomy

The importance of colorectal screening

HPA Magazine 22 // 2024

Colorectal cancer is the world's third most common cancer, representing approximately 10% of all cancers and corresponds one of the main causes of disability and death due to oncologic diseases worldwide. The reason for this numbers has to do with the timing of the diagnoses – i.e., it is usually detected in an advanced stage and at a time when the treatment options are quite limited.

Although more prevalent in the elderly, most cases occur in people over 50 years old, recent studies suggest that the prevalence of both benign and malignant neoplasms has risen among younger adults from some developed countries, that is, in people younger than 50 years of age.
The mortality rate associated with this type of cancer has risen 40% in the last 40 years, and an addition increment is expected to occur in the next 15 years, rising to a total of 13 million deaths due to cancer in the year 20230. The apparent increase in colorectal cancer in the so-called developed countries can be explained by the increase in population numbers, to the (bad) eating habits of those countries, and to the increase in already known risk factos: such as smoking, sedentary lifestyle and overweight.
New treatments for both patients in the early stages of cancers as well as metastatic cancer have been, and continue to be, developed which offer a higher survival/cure rate to those affected. In spite of this, these new treatment options have had a limited impact in the cure and survival rates on the long run.
As such, and due to the recognition that colorectal cancer has a precursor in the form of polyps, the available screening programs had gained importance worldwide. It is estimated that regular screening will have a great influence in the incidence and mortality due to colorectal cancer in the upcoming years, a result that most probably would not be gained with changes in lifestyle and/or availability of new therapeutic options.
The incidence and impact of colorectal cancer can be significantly reduced through the implementation of primary prevention strategies, such as adopting a healthy lifestyle, avoiding additional risk factors, and practicing early detection through systematic screening of the target population.
Prior conditions to a well-succeeded screening effect in regard to colorectal cancer are based on the fact that approximately 25% of western population between 50-79 years of age have polyps in both the colon and rectum, and that the transformation from benign to cancer cells takes between 10-15 yeas to accomplish. Also to be taken in consideration is the fact that these polyps have a high incidence with about 7000 new cases/year in Portugal alone, and potential for cure in the early stages of the disease
Worldwide screening aims therefore to detect early stages of the disease (polyps) and to subsequently remove the polyps in order to establish an early diagnosis of cancer, while in the asymptomatic phase, and as such to change the staging distribution so that a higher proportion of patients are detected in the early curable stage.
To accomplish this, screening methods can be divided in indirect, based on faeces, and direct or structural methods, based on biopsies, respectively. Those based of the analysis of faeces aim to detect the presence of microscopic bleeding, DNA markers or other biochemical products from intestinal neoplasms, with the possibility of additional colonoscopic screening to those who test positive. The structural methods correspond to an endoscopy (either sigmoidoscopy, colonoscopy or capsule colonoscopy) or a radiographic exam (CT colonography). There is by far more evidence supporting the use of detecting blood infaeces and sigmoidoscopy and colonoscopy, whereas other methods are still in an early stage of research/development and are not yet widely available for large population use.
Unilabs with its 15 endoscopic centres established in Portugal alone have contributed to the improvement of that which is considered to be the key to a positive outcome of the disease: its early detection. Anatomic pathology has, in turn, with the collaboration of gastroenterology and general medicine, had an added responsibility regarding the help and therapeutic orientation of the screening program in Portugal.

The Pathological Anatomy Laboratory has a vast team of differentiated pathologists who are dedicated to the different areas of the speciality. The gastrointestinal pathology department offers high-quality diagnostic cytology and histopathology in endoscopic biopsies and resections of the gastrointestinal tract, liver and pancreatobiliary system. 
Unilabs also has a multidisciplinary team highly specialised in conducting molecular biology studies, comprising doctors, biologists and qualified technicians. With this support, it is possible to offer a more accurate guidance in the treatment and follow-up of patients.
To support tumour classification, it is possible to carry out molecular analysis for mutations in genes such as BRAF and POLE, but the use of an NGS panel to search for actionable mutations in accordance with the National Comprehensive Cancer Network, the European Society for Medical Oncology and the American Society of Clinical Oncology guidelines is particularly important to the response to therapy.

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NGS (Next Generation Sequencing) - Somatic neoplasm panel
Through the simultaneous analysis of millions of DNA and RNA fragments, the NGS Panel for Somatic Neoplasms makes it possible to assess hotspot mutations, copy number variations (CNVs) and gene fusions in around 50 actionable genes for personalised therapies. With a commitment to providing its patients with the fastest and most robust response possible, Unilabs uses Ion Torrent Genexus System technology, which offers a maximum report turnaround time of 10 working days (after the sample is received in the laboratory).
This panel allows the testing of different types of samples, such as liquid biopsy, fine needle biopsy and FFPE (formalin-fixed, paraffin-embedded tissues), requiring only a small amount of biological material.
The panel has been validated for adenocarcinoma of the colon and rectum, among other neoplasms.

Details of the NGS panel for somatic neoplasms:
Hotspots DNA: AKT1, AKT2, AKT3, ALK, AR, ARAF, BRAF, CDK4, CDKN2A, CHEK2, CTNNB1, EGFR, ERBB2, ERBB3, ERBB4, ESR1, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, GNA11, GNAQ, GNAS, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MTOR, NRAS, NTRK1, NTRK2, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, ROS1, SMO e TP53.
CNVs: ALK, AR, CD274, CDKN2A, EGFR, ERBB2, ERBB3, FGFR1, FGFR2, FGFR3, KRAS, MET, PIK3CA e PTEN.
Inter- and intragenic fusions: ALK, BRAF, ESR1, FGFR1, FGFR2, FGFR3, MET, NRG1, NTRK1, NTRK2, NTRK3, NUTM1, RET, ROS1, RSPO2, RSPO3, AR, EGFR and MET.
It is also possible to detect some microorganisms that are co-factors in the carcinogenic process (see Pathological Anatomy Laboratory portfolio).