Translating clinical research of Molecular Biology into a personalized, multidisciplinary approach of colorectal cancer patients

Abstract

Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.

Keywords: KRAS; cancer; colorectal; instability; microsatellite.

Fig. 1

Immunohistochemical (IHC) analysis of mismatch repair proteins Negative staining (abnormal) for MLH1

Fig. 2

Suggested algorithm for molecular and genetic testing for Lynch syndrome IHC: Immunohistochemistry; MSI: Microsatellite instability; MMR: Mismatch Repair; MSS: microsatellite stable

Table 1

Amsterdam II criteria

Table 2

Revised Bethesda Guidelines

Fig. 3

Proposed decision algorithm for adjuvant therapy in colon cancer LN: Lymph nodes; CEA: Serum Carcinoembryonic Antigen; IHC: Immunohistochemistry; MSI: Microsatellite instability; MMR: Mismatch Repair; MSS: microsatellite stable; FOLFOX: 5-Fluoro-uracil (5-FU) +Leucovorin (LV) + Oxaliplatin; XELOX: Capecitabine + Oxaliplatin; Anti EGFR therapy - Epidermal Growth Factor Receptor Inhibitors (Cetuximab, Panitumumab)