EGFR expression in circulating tumor cells from high-grade metastatic soft tissue sarcomas

Braun, A.; Mello, Celso Abdon Lopes de; Corassa, Marcelo; Abdallah, Emne Ali; Urvanegia, Ana Claudia Machado; Alves, Vanessa da Silva; Flores, Bianca C. T.; Diaz, Mônica Taiane de Macêdo; Silva, Virgílio Souza e; Calsavara, Vinícius Fernando; Paterlini‐Bréchot, Patrizia; Chinen, Ludmilla Thomé Domingos

doi:10.1080/15384047.2018.1433498

Cited by 21 publications

(18 citation statements)

References 49 publications

(41 reference statements)

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“…To the best of our knowledge, this is the first study to find an association of low EGFR mRNA expression with tumor-specific survival in STS patients. An association of detection of EGFR positive STS cells with metastasis has been demonstrated [21]. However, we did not find such an association of the mRNA or protein level of EGFR or HIF-1α with the metastasis status of the investigated STS cohort.…”

Section: Discussioncontrasting

confidence: 83%

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Low HIF-1α and low EGFR mRNA Expression Significantly Associate with Poor Survival in Soft Tissue Sarcoma Patients; the Proteins React Differently

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et al. 2018

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In various tumors, the hypoxia inducible factor-1α (HIF-1α) and the epidermal growth factor-receptor (EGFR) have an impact on survival. Nevertheless, the prognostic impact of both markers for soft tissue sarcoma (STS) is not well studied. We examined 114 frozen tumor samples from adult soft tissue sarcoma patients and 19 frozen normal tissue samples. The mRNA levels of HIF-1α, EGFR, and the reference gene hypoxanthine phosphoribosyltransferase (HPRT) were quantified using a multiplex qPCR technique. In addition, levels of EGFR or HIF-1α protein were determined from 74 corresponding protein samples using ELISA techniques. Our analysis showed that a low level of HIF-1α or EGFR mRNA (respectively, relative risk (RR) = 2.8; p = 0.001 and RR = 1.9; p = 0.04; multivariate Cox´s regression analysis) is significantly associated with a poor prognosis in STS patients. The combination of both mRNAs in a multivariate Cox’s regression analysis resulted in an increased risk of early tumor-specific death of patients (RR = 3.1, p = 0.003) when both mRNA levels in the tumors were low. The EGFR protein level had no association with the survival of the patient’s cohort studied, and a higher level of HIF-1α protein associated only with a trend to significance (multivariate Cox’s regression analysis) to a poor prognosis in STS patients (RR = 1.9, p = 0.09). However, patients with low levels of HIF-1α protein and a high content of EGFR protein in the tumor had a three-fold better survival compared to patients without such constellation regarding the protein level of HIF-1α and EGFR. In a bivariate two-sided Spearman’s rank correlation, a significant correlation between the expression of HIF-1α mRNA and expression of EGFR mRNA (p < 0.001) or EGFR protein (p = 0.001) was found, additionally, EGFR mRNA correlated with EGFR protein level (p < 0.001). Our results show that low levels of HIF-1α mRNA or EGFR mRNA are negative independent prognostic markers for STS patients, especially after combination of both parameters. The protein levels showed a different effect on the prognosis. In addition, our analysis suggests a possible association between HIF-1α and EGFR expression in STS.

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Section: Discussioncontrasting

confidence: 83%

“…Finally, overexpression of EGFR protein was also demonstrated for soft tissue sarcoma [19,20]. However, the effect of EGFR on the metastasis status of STS patients is controversially discussed [14,21,22].…”

Section: Introductionmentioning

confidence: 99%

Low HIF-1α and low EGFR mRNA Expression Significantly Associate with Poor Survival in Soft Tissue Sarcoma Patients; the Proteins React Differently

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Täubert

Bache

et al. 2018

IJMS

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“…We evaluated CTCs and CTM in the blood of 55 patients diagnosed with nonmetastatic GAC, as well as their expression of HER2 and plakoglobin. In general, the median CTC count was high (2.8 CTCs per mL), compared with other publications that have employed the same ISET approach, such as metastatic breast, lung, and pancreatic cancers (respectively with 0.27, 2.3, and 0.67 CTCs per mL) [36], but similar compared with other tumors such as pancreatic cancer (1.2 CTCs per mL) [21], colon cancer (median of 2.0 CTCs per mL and 2.3 CTCs per mL) [34,37], and sarcomas (median of 2.0 CTCs per mL and 2.6 CTCs per mL) [12,38]. For head and neck cancer and lung cancer the median was very similar to our data for patients with GAC (3.0 CTCs per mL for both) [13,39].…”

Section: Discussionmentioning

confidence: 64%

“…Blood is particularly useful in the context of liquid biopsies (LBs), where it allows a series of approaches for the detection of informative markers. In oncology, LBs encompasses three main components: (a) the detection and quantification of cell-free tumor-derived DNA [5][6][7][8]; (b) the quantification and cargo determination of extracellular vesicles [9][10][11]; and (c) the detection, quantification, morphological analysis, and determination of biomarkers in circulating tumor cells (CTCs) [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

et al. 2019

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Background Gastric adenocarcinoma (GAC) is the third deadliest malignant neoplasm worldwide, mostly because of late disease diagnosis, low chemotherapy response rates, and an overall lack of tumor biology understanding. Therefore, tools for prognosis and prediction of treatment response are needed. Quantification of circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) and their expression of biomarkers has potential clinical relevance. Our aim was to evaluate CTCs and CTM and their expression of HER2 and plakoglobin in patients with nonmetastatic GAC, correlating the findings to clinicopathological data. Materials and Methods CTC enrichment was performed with isolation by size of epithelial tumor cells, and the analysis was performed with immunocytochemistry and microscopy. Two collections were made: one at diagnosis (55 samples before neoadjuvant treatment) and one after surgery and before adjuvant therapy (33 samples). Results A high detection rate of CTCs (90%) was observed at baseline. We evaluated HER2 expression in 45/55 biopsy samples and in 42/55 CTC samples, with an overlap of 36 subjects. Besides the good agreement observed for HER2 expression in primary tumors and paired CTCs for 36 cases (69.4%; κ = 0.272), the analysis of HER2 in CTCs showed higher positivity (43%) compared with primary tumors (11%); 3/5 patients with disease progression had HER2‐negative primary tumors but HER2‐positive CTCs. A significant CTC count drop in follow‐up was seen for CTC‐HER2‐positive cases (4.45 to 1.0 CTCs per mL) compared with CTC‐HER2‐negative cases (2.6 to 1.0 CTCs per mL). The same was observed for CTC‐plakoglobin‐positive cases (2.9 to 1.25 CTCs per mL). Conclusion CTC analysis, including their levels, plakoglobin, and HER2 expression, appears to be a promising tool in the understanding the biology and prognosis of GAC. Implications for Practice The analysis of circulating tumor cell levels from the blood of patients with gastric adenocarcinoma, before and after neoadjuvant treatment, is useful to better understand the behavior of the disease as well as the patients more likely to respond to treatment.

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“…Despite the absence of specific markers, various methods of cell isolation based on physical specificity (e.g., higher size and higher cell deformability of tumor cells) or biological properties (e.g., immunomagnetic isolation) have been proposed with success (Gabriel et al , 2016; Hayashi et al , 2017; Li et al , 2017). CTCs are detectable in bone sarcomas (Chinen et al , 2014; Benini et al , 2018) and STS patients (Braun et al , 2018; Mihály et al , 2018; Przybyl et al , 2019). To improve the sensitivity and specificity of detection and isolation of CTCs across sarcoma subtypes, investigators have been looking for universal sarcoma markers (Satelli et al , 2014; Li et al , 2018).…”

Section: Epidemiology Of Sarcomamentioning

confidence: 99%

Sarcoma treatment in the era of molecular medicine

et al. 2020

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Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult‐to‐treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.

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EGFR expression in circulating tumor cells from high-grade metastatic soft tissue sarcomas

Cited by 21 publications

References 49 publications

Low HIF-1α and low EGFR mRNA Expression Significantly Associate with Poor Survival in Soft Tissue Sarcoma Patients; the Proteins React Differently

Low HIF-1α and low EGFR mRNA Expression Significantly Associate with Poor Survival in Soft Tissue Sarcoma Patients; the Proteins React Differently

The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

Sarcoma treatment in the era of molecular medicine

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