Molecular Pathology: A Requirement for Precision Medicine in Cancer

Abstract

The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc.) to be applicable for formalin-fixed paraffin-embedded tissue. Reading a patient's tissue as ‘deeply' as possible and obtaining information on the morphological, genetic, proteomic and epigenetic background are the tasks of pathologists and molecular biologists and provide the clinicians with information relevant for precision medicine. Intensified cooperation between clinicians and pathologists will provide the basis of improved clinical drug selection and guide development of new cancer gene therapies and molecularly targeted drugs by research units and the pharmaceutical industry.

The Indirect Efficacy Comparison of DNA Methylation in Sputum for Early Screening and Auxiliary Detection of Lung Cancer: A Meta-Analysis

“…Lung cancer has become a global burden, further substantiating the need for early screening and auxiliary detection [ 1 , 3 ]. The key to accomplishing both these goals is the better understanding of the genes or pathways disrupted in causing lung cancer [ 6 , 45 , 59 ]. The fact that silencing genes through hypermethylation or activating genes through hypomethylation play an important role in the initiation and progression of lung cancer has stimulated the development of screening approaches to identify additional genes and pathways that are disrupted within the epigenome [ 59 ].…”

“…With the emergence and development of molecular epidemiology, which opens the “black box” of the disease process, molecular biomarkers have much potential to improve the understanding of the occurrence, development, and prognosis of disease for the early detection of these lesions at the pre-invasive stage, even predicting the progress of the disease [ 4 , 5 ]. Nowadays, it is clearly acknowledged that genetic alterations are accompanied by equally important epigenetic modifications in the pathogenesis of lung cancer [ 6 , 7 ]. In particular, DNA methylation is one of the earliest epigenetic modifications; it is closely associated with the occurrence and development of lung cancer, and it appears earlier than obvious malignant phenotype [ 7 ].…”

Evaluation of DNA and RNA quality from archival formalin‐fixed paraffin‐embedded tissue for next‐generation sequencing – Retrospective study in Japanese single institution

“…[1][2][3][4] However, in the treatment of tumors in which a genetic abnormality has been revealed, the application of molecularly targeted drugs has been evaluated after examining the expression of various molecules by immunochemical staining. [5][6][7][8][9] As the evaluation of gene abnormalities by IHC is limited, genetic analysis methods, such as fluorescence in situ hybridization and polymerase chain reaction (PCR), have been increasingly used in the detection of point mutations, insertion/deletions, and formation of fusion genes. [10][11][12][13][14][15][16][17][18][19][20] In addition, there are diverse types of cancer-specific target molecules, and a large number of molecular target drugs have been developed and used clinically.…”

Factors that drive the increasing use of FFPE tissue in basic and translational cancer research

“…Many molecular techniques for assessing aspects of DNA have been modified successfully for application to FFPE tissue (Dietel 2016). FFPE tissue can be used to detect chromosomal aberrations using microarray comparative genomic hybridization (Toffoli et al 2014, Pinto et al 2016.…”