GENCONCOR-1 study is translational research aimed to investigate the concordance of the molecular genetic profile of the primary tumor and brain metastases (BM) of colorectal cancer (CRC). The study was conducted by post hoc analysis of pairs of samples of histological material with determination of the mutational status of genes KRAS, NRAS, BRAF, HER2 and MSI.
Men and women over 18 years of age.
Histologically confirmed cancer of the colon or rectum.
Histologically confirmed metastatic lesion of the brain.
Neurosurgical resection for brain metastases of colorectal cancer.
Missing one sample from a pair of tumor samples.
Low quality or lack of tumor material for molecular genetic research.
Patients with metastatic colorectal cancer (CRC) and brain metastases (BM) will be analyzed according to sex, age, functional status (ECOG 0-1 or 2-3), number of BM (solitary or ≥ 2), clinical manifestations of BM (symptomatic or asymptomatic), extracranial lesions at the time of diagnosis BM (present or absent), course of brain metastases (synchronous with the primary tumor or metachronous), side of the location of the primary tumor (left-sided or right-sided CRC), location of intracranial lesions (supratentorial or subtentorial), number of previous lines of drug therapy.
Cohort
Retrospective
Tumor samples will be tested for mutation status of KRAS, NRAS, BRAF, HER2 and MSI
Diagnostic testFor molecular genetic research, archival formalin-fixed and paraffin-embedded tumor blocks will be used. Research method - HRM-PCR sequencing to determine mutation status of KRAS, NRAS and BRAF (RotorGene 6000, ABI Prism 3500) and fragmentation analysis to determine MSI (ABI Prism 3500) Subject to study: mutations in the KRAS, NRAS, BRAF genes, as well as MSI status and HER2neu expression (± amplification) Somatic mutations in the RAS family genes are planned to be studied in exons 2 (codons 12 and 13), exon 3 (codon 61) and exon 4 (codon 146). In the case of the BRAF gene - exon 15 (codons 597-601). Determination of microsatellite instability is planned using five markers: BAT25, BAT26, NR21, NR24, NR27, associated with structural and functional disorders of the DNA unpaired base repair system. Assessment of HER2 gene status is planned by immunohistochemical (IHC) screening of HER2neu expression. IHC-screening of HER2-status will be performed using an antibody clone 4B5 (Ventana).
Concordance rate (%)
Concordance rate (%) between mutational status of the brain lesions and their corresponding primary tumor. Calculated as the ratio of concordant cases to total cases.
Intracranial progression-free survival (CNS-PFS1)
Time from the date of cancer diagnosis to the date of detection of brain metastases.
Overall survival (OS)
Time from the date of detection of brain metastases to the date of death.
Intracranial progression-free survival (CNS-PFS2)
Time from the date of neurosurgical resection to the date of intracranial progression (continued growth or distant brain metastases) or death.
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