Switch in KRAS mutational status during an unusual course of disease in a patient with advanced pancreatic adenocarcinoma: implications for translational research

• Published in: BMC cancer Vol. 17; no. 1; pp. 374 - 5
• Main Authors: Baechmann, Sibylle, Ormanns, Steffen, Haas, Michael, Kruger, Stephan, Remold, Anna, Modest, Dominik Paul, Kirchner, Thomas, Jung, Andreas, Werner, Jens, Heinemann, Volker, Boeck, Stefan
• Format: Journal Article
• Language: English
• Published: England BioMed Central 26.05.2017; BMC
• Subjects: Adenocarcinoma; Aged; Biomarkers; Biopsy; Cancer therapies; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - therapy; Case Report; Chemoradiotherapy; Chemoradiotherapy - methods; Chemotherapy; Clinical trials; Colorectal cancer; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease; Disease control; Epidermal growth factor; Epidermal growth factor receptors; Evolution & development; Female; Fluorouracil - therapeutic use; Gemcitabine; Genes; Humans; K-Ras protein; Kinases; KRAS mutation; Lymph; Lymph nodes; Lymphatic system; Medical prognosis; Metastasis; Mutation; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; Oncology; Oral cavity; Paclitaxel; Pancreas; Pancreas transplantation; Pancreatic cancer; Pancreatic ductal adenocarcinoma (PDAC); Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pancreaticoduodenectomy; Patients; Point mutation; Proto-Oncogene Proteins p21(ras) - genetics; Survival; Translation; Translational Research, Biomedical; Tumor heterogeneity; Tumors; Tumor heterogeneity; KRAS mutation; Pancreatic ductal adenocarcinoma (PDAC)
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-017-3376-4

Despite the introduction of novel effective treatment regimens like gemcitabine plus nab-paclitaxel and FOLFIRINOX, pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive epithelial tumors. Among the genetic alterations frequently found in PDAC, mutations in the KRAS gene might play a prognostic role regarding overall survival and may also have the potential to predict the efficacy of anti-EGFR treatment. We report the clinical case of a 69 year old Caucasian female that was diagnosed with histologically confirmed locally advanced PDAC with lymph node involvement in August 2010. At the time of first diagnosis, tumor tissue obtained from an open regional lymph node biopsy showed a poorly differentiated adenocarcinoma with a wild type sequence within exon 2 (codon 12/13) of the KRAS gene. The patient initially received single-agent gemcitabine and a subsequent 5-FU-based chemoradiotherapy with a sequential maintenance chemotherapy with oral capecitabine resulting in a long term disease control. Local disease progression occurred in May 2014 and the patient underwent pancreaticoduodenectomy in September 2014. A novel KRAS gene mutation (c.35G > T, p.G12 V) in exon 2 (codon 12) was detected within the surgical specimen. As of January 2016 the patient is still alive and without evidence of the underlying disease. Specifically in the context of clinical trials and translational research in PDAC a re-assessment of molecular biomarkers, i. e. KRAS, at defined time points (e. g. relapse, disease progression, unusual clinical course) may be indicated in order to detect a potential switch in biomarker status during the course of disease.