ABSTRACT
Testing for mutations in the KRAS oncogene for patients with metastatic colorectal cancer (mCRC) is generally performed using DNA from formalin-fixed paraffin-embedded tumor tissue; however, access to specimens can be limited and analysis challenging. This study assessed the identification of KRAS mutations in circulating free DNA (cfDNA) using a commercially available KRAS polymerase chain reaction (PCR) kit. Matched plasma, serum and tumor samples were available from 71 patients with mCRC who had received prior therapy but whose disease progressed following therapy. Yields of cfDNA from plasma and serum samples were comparable. Analyses were successful in 70/71 plasma-extracted samples (specificity: 97%, sensitivity: 31%) and 67/71 serum- extracted samples (specificity: 100%, sensitivity: 25%). This study demonstrates that KRAS mutations can be detected in cfDNA using a commercially available KRAS PCR kit, confirming cfDNA as a potential alternative source of tumor DNA in a diagnostic setting if access to archival tumor specimens is limited.
ABSTRACT
BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome that includes gastro-duodenal involvement, polyposis, and a propensity to adenocarcinoma necessitating endoscopic surveillance. There are few data describing pediatric upper gastrointestinal FAP resulting in conflicting screening recommendations. OBJECTIVES: To characterize pediatric gastroduodenal FAP and to investigate the association between symptoms at endoscopy and APC mutation analysis with endoscopic-histologic findings warranting surveillance. METHOD: A retrospective chart review was performed, including all children with FAP who underwent upper endoscopy (EGD) at two institutions; (UNMC: 1992-2002, JHH: 1983-2002), all biopsies were reviewed and the APC mutations present in the cohort of patients were correlated to the pattern of severity of endoscopic findings and the frequency of APC mutations identified through commercially available testing for FAP (Labcorp: 1998-2002). RESULTS: Twenty-four patients from 21 families underwent 49 EGDs. Eighty-three percent were asymptomatic at the time of endoscopy. The most common finding was fundic gland polyposis (FGP) (51%), of which 42% and 15% harbored dysplasia and changes indefinite for dysplasia, respectively. Periampullary duodenal adenomata were present in 41% of patients with one patient necessitating ampullectomy. Symptoms at endoscopy were not predictive of premalignant changes. In 15 patients where the APC mutation was known patients with dysplastic FGP, gastric, or duodenal adenoma were more likely to harbor a mutation between codons 1225-1694 than the reference population (p= 0.006). CONCLUSIONS: All pediatric patients with FAP warrant upper gastrointestinal screening and surveillance endoscopy from the time of initial colonoscopy irrespective of referable symptoms. Patients with APC mutation between codon 1225-1694 may be more susceptible to aggressive gastroduodenal involvement in FAP.
