Researchers at the MDC, the BIH and Charité have developed methods for performing comprehensive analyses of fixed tumor tissue samples. These analyses make it possible to shed new light on the clinical course of various cancer types, as the team reports in Nature Communications.
Today as they did 100 years ago, doctors diagnose cancer by taking tissue samples from patients, which they usually fix in formalin for microscopic examination. In the past 20 years, genetic methods have also been established that make it possible to characterize mutations in tumors in greater detail, thus helping clinicians select the best treatment strategy.
A tumor section, with a mass spectrometer visible in the background.
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Now, a group of researchers from the Berlin-based Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), the Berlin Institute of Health (BIH), Charité – Universitätsmedizin Berlin and the German Cancer Consortium (DKTK) have succeeded in analyzing in detail more than 8,000 proteins in fixed samples of lung cancer tissue using mass spectrometers.
"Using the methods we have developed, it has become possible to conduct an in-depth analysis of molecular processes in cancer cells at the protein level – and to do so in archived patient samples that are collected and stored in large numbers in everyday clinical practice," says Dr. Philipp Mertins, head of the Proteomics Platform at the MDC and the BIH. "Even very small tissue samples, such as those obtained in needle biopsies, are sufficient for our experiments."
The team of researchers, led by Mertins and Prof. Frederick Klauschen from the Institute of Pathology at Charité, has been able to show that proteins – unlike the frequently studied yet quite sensitive RNA molecules – remain stable in the samples for many years and can be precisely quantified. "In addition, the proteins that are present in the tumor tissue map disease progression especially well," says lead author Corinna Friedrich, a PhD student in the labs of Mertins and Klauschen. "This is because they provide information about such things as which of the genes that promote or inhibit tumor growth are particularly active in the cells."
The picture gained from the team's analysis of two forms of lung cancer – adenocarcinomas and squamous cell carcinomas – has also become so detailed because the researchers have not only uncovered a great many of the proteins present in the cell, but have also quantified more than 14,000 phosphosites. With the help of phosphorylation, a mechanism that regulates the reversible attachment of phosphate groups to proteins, the cell controls almost all biological processes by switching certain signaling pathways on or off.
"Our paper thus provides a good basis for gaining a better understanding of disease progression in lung cancer and also in other types of cancer," says Klauschen, who, along with Mertins, is co-corresponding author of the study. Klauschen has since become director of the Institute of Pathology at Ludwig-Maximilians-Universität München, but continues to conduct research at Charité. "The methods we have developed will also enable us to better explain in the future why a very specific therapy works for some patients but not for others," adds the pathologist. This will, he says, make it easier, to find the best treatment option for each patient.
MEDICA-tradefair.com; Source: Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)