Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy; Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, 67100 L'Aquila, Italy.
Hum Pathol. 2018 Apr;74:178-182. doi: 10.1016/j.humpath.2018.01.021. Epub 2018 Jan 31.
We describe a metastatic colorectal cancer patient, treated with first-line 5-fluorouracil, irinotecan, bevacizumab, and oxaliplatin (FIr-BFOx) therapy, with aggressive and resistant disease. KRAS, NRAS, BRAF, and 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 2 rare PI3KCA mutations (c.1633G>C and c.1645G>C). The c.1645G>C was never reported in colorectal cancer. Akt/p-Akt, phosphatase and tensin homolog, mismatch repair, and epidermal growth factor receptor expression was evaluated. Normal mismatch repair and epidermal growth factor receptor expression was detected. Akt was shown by primary tumor and liver metastasis, whereas p-Akt was identified only in the latter, despite positive phosphatase and tensin homolog expression. Patient showed 7 months of progression-free survival and 15 months of overall survival, lower than median values reported in KRAS exon 2-mutant patients treated with the same therapy. Results lead to the hypothesis of a putative role of these mutations in worsening of the disease and are open to further confirmatory studies.
我们描述了一位转移性结直肠癌患者，该患者接受了一线 5-氟尿嘧啶、伊立替康、贝伐单抗和奥沙利铂（FIr-BFOx）治疗，但疾病进展迅速且具有耐药性。在原发性肿瘤和肝转移灶中分析了 KRAS、NRAS、BRAF 和 PI3KCA。在原发性肿瘤和肝转移灶中检测到 KRAS c.34G>A 突变，此外还发现了 2 种罕见的 PI3KCA 突变（c.1633G>C 和 c.1645G>C）。c.1645G>C 在结直肠癌中从未报道过。评估了 Akt/p-Akt、磷酸酶和张力蛋白同源物、错配修复和表皮生长因子受体表达。检测到正常的错配修复和表皮生长因子受体表达。在原发性肿瘤和肝转移灶中均检测到 Akt，但仅在后者中检测到 p-Akt，尽管磷酸酶和张力蛋白同源物表达为阳性。患者无进展生存期为 7 个月，总生存期为 15 个月，低于接受相同治疗的 KRAS 外显子 2 突变患者的中位值。结果提示这些突变可能在疾病恶化中起作用，有待进一步的确认性研究。
