KRAS and Two Rare PI3KCA Mutations Coexisting in a Metastatic Colorectal Cancer Patient With Aggressive and Resistant Disease.

We describe a metastatic colorectal cancer (mCRC) patient, treated with first-line FIr-B/FOx (5-fluorouracil, irinotecan, bevacizumab, oxaliplatin) therapy, with aggressive and resistant disease. KRAS, NRAS, BRAF, PI3KCA were analyzed in primary tumor and liver metastasis. KRAS c.34G>A mutation was detected in primary tumor and liver metastasis, which, additionally, revealed two rare PI3KCA mutations (c.1633G>C, c.1645G>C). The c.1645G>C was never reported in CRC. Akt/p-AktSer473, PTEN, mismatch repair (MMR), epidermal growth factor receptor (EGFR) expression was evaluated. Normal MMR and EGFR expression was detected. Akt was shown by primary tumor and liver metastasis, whereas p-AktSer473 was identified only in the latter, despite positive PTEN expression. Patient showed 7months progression free survival and 15months overall survival, lower than median values reported in KRAS exon 2 mutant patients treated with the same therapy. Results leave to hypothesize putative role of these mutations in worsening of the disease and open to further confirmatory studies.