Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma.

The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.

Nasoethmoidal Intestinal-Type Adenocarcinoma Treated with Cetuximab: Role of Liquid Biopsy and BEAMing in Predicting Response to Anti-Epidermal Growth Factor Receptor Therapy.

Sinonasal intestinal-type adenocarcinomas (SNS-ITAC) are very rare tumors that resemble colorectal cancer in many of their pathological and molecular characteristics. Indeed, in most published series, 10%-14% of SNS-ITAC harbor mutations in KRAS. There is no standard systemic treatment in recurrent or metastatic SNS-ITAC, and there is no evidence of the use of any targeted agent in this entity. We present the case of a recurrent nasoethmoidal ITAC informed as RAS and BRAF wild-type by standard real-time polymerase chain reaction methods and treated with first-line cetuximab and irinotecan without response. Circulating tumor cells coupled to highly sensitive DNA analyses unveiled a mutation in KRAS exon 2 codon 12. Subsequent studies in the primary tumor using BEAMing detected a mutation in the same codon, confirming the KRAS mutated status of the tumor, and possibly explaining the absence of treatment response. This case exemplifies how liquid biopsy can aid in the correct and real-time molecular characterization of tumors even in a rare nonmetastatic cancer of the head and neck. KEY POINTS: Sinonasal intestinal type adenocarcinomas (SNS-ITAC) are rare tumors that commonly develop after a prolonged exposure to organic dusts (wood, leather, etc.), and that resemble colorectal cancer in some of their morphological and molecular characteristics.KRAS mutations have been described in 10%-14% in most series. However, its predictive value for guiding treatment decisions with targeted therapies (i.e., anti-epidermal growth factor receptor [EGFR] therapy) has not been defined.The first case of an SNS-ITAC treated with anti-EGFR therapy (cetuximab) is reported. Analysis of DNA from circulating tumor cells (CTCs) unveiled a mutation in KRAS not detected by standard methods in the primary tumor. However, RAS analysis using BEAMing detected a mutation in the primary tumor in the same codon of KRAS originally detected in CTCs, altogether possibly explaining the lack of treatment response.Liquid biopsy may allow for an accurate molecular diagnosis in rare, organ-confined tumors where few therapeutic options exist. Highly sensitive molecular diagnostics may aid in better characterizing rare entities harboring potentially druggable targets.

Vascular Endothelial Growth Factor (VEGF) Polymorphisms and Serum VEGF Levels in Women With Epithelial Ovarian Cancer, Benign Tumors, and Healthy Ovaries.

OBJECTIVE: This study analyzed the relation of 5 single-nucleotide polymorphisms (SNPs) in the VEGF (vascular endothelial growth factor) gene in patients with epithelial ovarian cancer (EOC), compared with patients carrying benign tumors or healthy ovaries. We studied serum VEGF levels and the relation with SNPs and association between VEGF SNPs and haplotypes with progression-free survival (PFS) in patients with cancer. METHODS: The genotyping of VEGF gene polymorphisms (-2578 C/A, -1154 G/A, -460 T/C, +405 G/C, +936 C/T) was performed in DNA isolated from blood samples of 100 women. The different genotypes were evaluated by quantitative real-time polymerase chain reaction. Vascular endothelial growth factor protein concentration was assessed in serum using solid-phase sandwich enzyme-linked immunosorbent assay. RESULTS: We found statistically significant differences in the distribution of VEGF genotypes among the 3 groups of patients: -2578 C/A between those with EOC and healthy ovary (P = 0.04), -460 T/C between those with EOC and healthy ovary (P = 0.03), and -460 T/C between those with benign tumors and healthy ovary (P = 0.02). Vascular endothelial growth factor serum levels were analyzed in patients with EOC. Higher levels were found in patients with clear cell carcinoma compared with those with serous, mucinous, or endometrioid tumors (P < 0.05). No clear association was observed between VEGF SNPs and serum VEGF levels. There was no significant correlation between VEGF SNPs and PFS. In haplotype analysis, CGTCT and CGTGT showed worse prognosis without reaching the statistical significance. CGCGC and AGTGC haplotypes had statistically significant differences among patients with EOC, benign tumors, and healthy ovaries (Ps = 0.046 and 0.041, respectively). CONCLUSIONS: The distribution of VEGF genotypes was different in patients with EOC, compared with those with benign tumors or women with healthy ovaries. Vascular endothelial growth factor serum levels were higher in patients with clear cell carcinoma. No correlation was found with improved PFS, but CGTCT and CGTGT haplotypes showed worse prognosis.