Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

Abstract

BackgroundTechniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment.MethodsReconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas.ResultsSeven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival.ConclusionFor the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further.

Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma

“…Herein, we collected PBMCs from 111 NSCLC patients to detect the target genes’ expression originating from epithelium instead of acquiring and examining the CTCs. The elevated levels of gene expression from epithelial origin indicate the existence of CTCs or circulating tumor nuclei in peripheral blood; these cannot be detected in the normal peripheral blood [17,18]. Lung cancer is a heterogeneous disease with respect to histological and biological characteristics [19].…”

“…Lung cancer is a heterogeneous disease with respect to histological and biological characteristics [19]. Owing to the heterogeneity of the tumor cells and the limited reliability of single marker, we selected four genes of epithelial origin, described previously, for the analysis of gene expression [17,18]. These four markers cannot be detected in normal mononuclear cells by optimized experiments and are specific for the detection of circulating epithelial cells [12].…”

Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor patients

“…While it is accepted that circulating tumor DNA is detectable in the blood stream of a subset of patients with solid tumors, including bladder cancer, 46-51 HNSCC, [52][53][54][55] and ovarian cancer, [56][57][58][59] it is improbable that the observed methylation differences in peripheral blood between cancer cases and controls are driven by this phenomenon, particularly in the absence of enrichment for free DNA in the plasma, as circulating tumor DNA, when present, occurs at an extremely low concentration in blood 60 and, thus, would have a negligible impact on the methylation signature of peripheral blood. The analytic applications presented here required high-density epigenome-wide methylation data from sorted non-pathologic human leukocyte samples for the identification of putative leukocyte lineage-specific DMPs, along with corresponding epigenomic data for the peripheral blood samples from the Epigenome-wide analysis of cancer-associated DNa methylation and shifts in leukocyte composition in peripheral blood for bladder, head and neck (hNscc) and ovarian cancers.…”

The role of nitric oxide in the induction of caudal-type homeobox 2 through epidermal growth factor receptor in the development of Barrett's esophagus

“…The gene-specific primers for human CDX2 (328-bp PCR product) [41] were CDX2 forward: 5¢-AGTGGTGTACACGGACCAC-CAGCGG-3¢ and CDX2 reverse: 5¢-AACCCCAG GGACAGAGCCAGACAC-3¢. The gene-specific primers for human EGFR (337-bp PCR product) [42] were EGFR forward: 5¢-TGTGAGGTGGTCCTT GGGAATTTGG-3¢ and EGFR reverse: 5¢-TGCT GACTATGTCCCGCCACTGGA-3. The primers for G3PDH (983-bp PCR product) were G3PDH forward: 5¢-TGAAGGTCGGAGTCAACGGATTT GGT-3¢ and G3PDH reverse: 5¢-CATGTGGGC-CATGAGGTCCACCAC-3¢.…”