Molecular pathology in lung cancer: a guide to the techniques used in clinical practice

Abstract

Five year survival rates for lung cancer patients are poor; however the development of new therapeutic options, which benefit subsets of the population, offer hope of improvement. These novel therapies frequently rely upon the analysis of biomarkers in pathology samples; in lung cancer patients, testing is now routinely carried out to identify small mutations and chromosomal rearrangements in order to predict response to treatment. The recent increase in biomarker analyses in pathology samples has lead to the development of a new specialty, molecular pathology. The use of molecular pathology assays in clinical samples is largely under the control of the histopathologist; who is likely to be asked, as a minimum, to select tissue sections for molecular analysis and mark areas of H&E stained slides for macro or microdissection. Many histopathologists will also be involved in the sourcing and implementation of new assays. This review aims to provide a guide to some of the most commonly used molecular pathology methods - their advantages and their limitations.

DACH1 inhibits the proliferation and invasion of lung adenocarcinoma through the downregulation of peroxiredoxin 3

“…In the past 100 years, lung cancer has been transformed from a rare disease into a serious global problem [ 1 , 4 ]. Although significant advances have been made with conventional therapies, lung cancer still remains the leading cause of cancer-related mortality among both men and women [ 1 , 4 , 5 ], the fact of which calls for improvements in the diagnosis and treatment of the disease. Although the EGFR tyrosine kinase inhibitors gefitinib and erlotinib have revolutionized the treatment of lung cancers, only patients with activating mutations of the EGFR gene respond to the therapy [ 9 ].…”

“…Lung cancer is the leading cause of cancer-related mortality among both men and women worldwide with approximately 160,000 deaths reported each year in the USA [ 3 , 4 ]. Non-small cell lung cancer (NSCLC) constitutes approximately 80 % of all lung cancers and includes adenocarcinoma and squamous cell carcinoma, which are histologically distinct from small cell lung cancer [ 5 ]. Although significant advances have been made with conventional therapies, including surgery, chemotherapy, and radiotherapy, the poor prognosis and low overall survival (OS) rate highlights the urgent need for developing novel therapeutic methods [ 6 ].…”

Clinical feasibility of NGS liquid biopsy analysis in NSCLC patients

“…The FFPE material has several advantages since it is a widely available material, easy to use and store [5, 6]. In addition, it provides the possibility of selecting the most appropriate cancer tissue either by microdissection or by macrodissection, increasing the sensitivity of somatic mutation detection assays [7, 8]. However, FFPE material also has several disadvantages, such as its unavailability in cases of inoperable tumors and its inability in some cases to capture the tumor’s heterogeneity [9].…”

A large-scale, multicentered trial evaluating the sensitivity and specificity of digital PCR versus ARMS-PCR for detecting ctDNA-based EGFR p.T790M in non-small-cell lung cancer patients

“…Additionally, ADx-ARMS ® EGFR mutation detection kit required 10 ng of input DNA per reaction for a limit of detection of 1% mutant allele frequency, or 6-7 copies/reaction (33). Another source did site the LoD for ADx-ARMS PCR ranges from 0.5% to 7.02% depending on the mutation, but which mutation corresponded to what LoD was not described and the input amount of DNA to achieve that LoD was not described as well (34). On the other hand, the dPCR detection kit used 20 ng of input DNA making the limit of detection around 6-7 copies/ reaction.…”