Lung cancer is one of the most common malignant diseases in humans and is also the cancer with the highest mortality worldwide.
As pulmonary carcinomas usually we denote malignant tumors arising from the lung tissue, in many cases from the cells of the alveoli or the cells lining the respiratory tract (bronchi). Typically, lung cancer is asymptomatic in early stages, which often results in a late diagnosis and a more complicated treatment.
Clinical examination in patients with lung carcinoma at the University Hospital Ulm
50 lung cancer patients (2 SCLC and 48 NSCLC) stage IIIA to IV were enrolled in this clinical trial [Gorges et al., 2015]. One goal of the study was the isolation of EpCAM-positive CTCs from the peripheral blood of patients before chemotherapy and 12 weeks after initiation of therapy. To assess the reproducibility of the method, two replicate applications were performed during each visit. The isolated CTCs were analyzed by specific immunofluorescence staining and enumerated. 108 out of 185 (58%) of the samples were identified as CTC positive. The GILUPI CellCollector® detected significantly more CTCs compared to 27%.
In addition, mutational analyzes were performed. Of two patients with known mutational status in the KRAS and EGFR genes of the primary tumor, the isolated CTCs were examined by digital PCR. The mutation status of the CTCs was consistent with that of the primary tumor.
Prostate cancer is by far the most common type of cancer in men in Germany. Worldwide, it is the second most common male cancer after lung cancer.
It is a malignant tumor disease originating from the glandular tissue of the prostate gland.
Clinical examination in patients with prostate cancer
In this study, it was investigated whether a combination of in vivo isolated CTCs with downstream mRNA analysis is suitable for optimizing the individual treatment of prostate cancer patients [Markou et al., 2017]. For this, EpCAM-positive CTCs were isolated in vivo with the GILUPI CellCollector® from 105 patients. In addition, 36 healthy volunteers were examined. For the molecular characterization of CTCs a test procedure for the detection of 14 gene products (mRNAs) was used.
High heterogeneity of these gene products was observed in the CTCs. In the vast majority of patients (70.5%) at least one gene product was elevated, but not in the healthy. In addition, at least two gene products were elevated in 41% of patients and as many as three in 15% of patients.
In addition, it was shown that the molecular profile of the CTCs changed after treatment.
Gene products of CTCs before and after therapy [“Multiplex Gene Expression Profiling of In Vivo Isolated Circulating Tumor Cells in High-Risk Prostate Cancer Patients”, Markou et al., 2017Clin Chem. 2018 Feb;64(2):297-306. doi: 10.1373/clinchem.2017.275503. Epub 2017 Nov 9, http://www.clinchem.org/, Copyright Clinical Chemistry | All Rights Reserved]
Clinical examination in patients with prostate cancer using new, innovative padlock assays
For this study at the University of Graz, the GILUPI CellCollector® was used in patients with prostate cancer and pancreatic carcinoma. Subsequently, CTCs were counted and the detection of mRNA transcripts (gene products) carried out using a newly developed in situ Padlock probe assay. This method allows e.g. the quantitative analysis of mRNA expression on therapy-relevant cancer markers [El-Heliebi et al, .2018].
In summary, CTCs were detected in 62% of prostate cancer and 47% of pancreatic cancer patients. Therapeutically relevant cancer markers (eg, AR-V7 transcripts or KRAS mutations) have been identified in the majority of these cells.
Identification of cancer markers on CTCs from prostate cancer patients [“In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells“, El-Heliebi et al., 2018, Clin Chem. 2018 Mar;64(3):536-546. DOI: 10.1373/clinchem.2017.281295 Published February 2018, http://www.clinchem.org/, Copyright Clinical Chemistry | All Rights Reserved]