CK19, CK20, EGFR and HER2 Status of Circulating Tumor Cells in                     Patients with Breast Cancer

Tunca, Berrin; Egelí, Ünal; Çeçener, Gülşah; Tezcan, Gülçin; Gökgöz, Şehsuvar; Taşdelen, İsmet; Bayram, Nuran; Tolunay, Şahsine; Umut, Gorkem; Demirdöğen, Elif; Ertürk, Elif; Ak, Seçil; Çetintaş, Sibel Kahraman; Evrensel, Türkkan

doi:10.1177/030089161209800211

Cited by 17 publications

(20 citation statements)

References 49 publications

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“…As fibrous tissue proteins distributed in epithelial cells, the CK protein family participates in the formation of the cytoskeleton and in regulation of cell differentiation and movement (Tunca et al, 2012). Recently, the CK20 protein has received increased interest due to its highly specific expression in both colorectal and gastric cancers (Kim et al, 2009;Sun et al, 2012;Kim et al, 2013;Tunca et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Predictive value of CK20 in evaluating the efficacy of treatment and prognosis after surgery for colorectal cancer

Li¹,

Xiao²,

Hong³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Herein, correlations between expression levels of CK20 and efficacy of treatment and postoperative prognosis of colorectal cancer were evaluated to elucidate the clinical value of CK20. Postoperative follow-up was performed on 62 patients who underwent surgery for colorectal cancer between January 2010 and December 2010. Samples of tumor tissues and intraperitoneal drainage fluids were collected. Blood samples were obtained during the 2-year follow-up period. The expression of CK20 in surgical specimen, intraperitoneal drainage fluids, and postoperative serum samples was quantified by enzyme-linked immunosorbent assay, RT-PCR, and western blotting. Correlation between the levels of CK20 and postoperative outcomes was investigated by Spearman correlation analysis. In both tumor specimens and intraperitoneal drainage fluids, CK20 levels were lower in patients with earlier cancer stages than in those at later stages. During postoperative follow-up, serum negative CK20 patients had significantly higher 3-year survival rates than serum positive CK20 patients. All differences were statistically significant (P < 0.05). CK20 levels can provide clinically valuable information on the postoperative prognosis of patients with colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Predictive value of CK20 in evaluating the efficacy of treatment and prognosis after surgery for colorectal cancer

Li¹,

Xiao²,

Hong³

et al. 2015

Genet. Mol. Res.

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“…We showed that C20 positivity was more frequent in BC patients with aggressive tumors compared to other BC patients. On the other hand, mRNA expression of CK19, EGFR and HER2 was not significantly associated with the clinical and pathological characteristics of BC patients [6]. Although our previous findings indicate a potential relationship between these CTMs and aggressive tumor characteristics in BC, two facets related to the clinical utility of CTMs remained unaddressed as follows: 1) the predictive ability of CTMs for both local recurrence and distant metastasis and 2) the effect of therapy on CTM ability to predict distant metastasis.…”

Section: Introductionmentioning

confidence: 56%

“…In a previous study [6], we analyzed the prognostic importance of the circulating tumor markers (CTMs) cytokeratin 19 (CK19), CK20, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in BC. We showed that C20 positivity was more frequent in BC patients with aggressive tumors compared to other BC patients.…”

Section: Introductionmentioning

confidence: 99%

Prediction of breast cancer metastasis risk using circulating tumor markers: A follow-up study

Çetintaş

Tezcan

Tunca

et al. 2018

Bosn J of Basic Med Sci

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Distant organ tumor dissemination is a major cause of breast cancer-related deaths. In 2010, we analyzed the prognostic importance of the circulating tumor markers (CTMs) cytokeratin 19 (CK19), CK20, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in relation to the clinical and pathological characteristics of patients with breast cancer (BC). To assess the clinical utility of CK19, CK20 and EGFR in predicting distant metastasis in BC, here we report 7-year follow-up results of 77 patients. The patients with at least one positive CTM were classified as CTM(+) and those negative for all CTMs were assigned to CTM(-) group. In patients who received no treatment following CTM analysis, 25.0% had metastasis in CTM(+) and 10.0% in CTM(-) group. In patients who received one of the following therapies: chemotherapy, radiotherapy or hormone therapy, or the combinations of these therapies, the rate of metastasis was 33.3% in CTM(+) and 20.0% in CTM(-) group. Disease-free time was shorter in CTM(+) patients compared to CTM(-) group (28.83 ± 10.76 and 41.38 ± 9.5 months, respectively). According to multivariate Cox proportional hazard regression analysis, the presence of regional lymph node metastasis, Ki-67 expression, higher tumor grade and CTM expression status were predictors of poor prognosis associated with distant metastasis (p < 0.05). Also, CTM positivity was a factor associated with metastasis-related poor prognosis (HR = 0.492, p = 0.026). The mean survival for CTM(+) patients was shorter than that for CTM(-) patients (90.671 ± 2.66 and 101.23 ± 3.92 months, respectively; p > 0.05). Our findings demonstrate that CTM positivity may indicate a high metastasis risk; however, CTM negativity does not guarantee low metastasis risk. These results may encourage further preclinical investigation of CTMs, to evaluate the possible implications of these findings to the clinical setting.

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“…We decided to concentrate on the following genes: Cytokeratin 19, which is also used in the immunohistochemical detection of cancer cells (APAAP-staining) (21,22) and is a marker for shorter disease free survival and reduced overall survival in breast cancer patients (23)(24)(25)(26). Furthermore it is especially expressed in metastatic breast cancer cells (27,28) and was already used as a biomarker for CTCs in the blood of breast cancer patients (29). Furthermore CK19 was shown to be expressed in CTCs from early and metastatic breast cancer patients, together with the EMT-markers Twist and Vimentin (30), so it could be concluded, that this epithelial marker is not downregulated by EMT.…”

Section: Introductionmentioning

confidence: 99%

Epithelial‑mesenchymal transition was identified as a potential marker for breast cancer aggressiveness using reverse transcription‑quantitative polymerase chain reaction

et al. 2018

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The primary cause of breast cancer‑associated mortality is the formation of distant metastasis. During the metastatic process, single tumor cells dissolve from the primary tumor site and undergo various changes in cell adhesion and motility properties. The tumor cells invade the blood stream and travel to different sites of the body, where they may initiate outgrowth. These cells are referred to as circulating tumor cells (CTCs). The process of changing cellular properties is known as epithelial to mesenchymal transition (EMT). As a different set of genes is upregulated during EMT, such genes may serve as marker genes for the detection of CTCs based on reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Therefore, EMT‑ and breast cancer‑related genes were selected as RT‑qPCR markers. These genes were tested for performance in a model system of blood samples from healthy donors, to which a number of various breast cancer cell lines were added. The genes with optimal performance were subsequently used in RT‑qPCR with 35 breast cancer patient samples. The genes which showed the highest and most consistent increase in gene expression with the increase in the number of cancer cell line cells added were CK19, Snail, FoxC2 and Twist. Following RT‑qPCR for all patient samples, two subgroups were arranged: One group in which all genes were downregulated and the second group with at least one gene indicated an upregulation of gene expression. Comparisons were made between the tumour characteristics from these two groups. Results suggested that carcinomas of the first group exhibited a less aggressive tumor biology compared with those in the second group. The present study indicated a novel RT‑qPCR based test for tumor malignancy.

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CK19, CK20, EGFR and HER2 Status of Circulating Tumor Cells in Patients with Breast Cancer

Abstract: The results suggest that the investigation of CK20 mRNA with other biomarkers in the peripheral blood of breast cancer patients may be useful to monitor the presence of disseminated tumor cells in the blood circulation and to predict the prognosis of breast cancer.

Cited by 17 publications

References 49 publications

Predictive value of CK20 in evaluating the efficacy of treatment and prognosis after surgery for colorectal cancer

Predictive value of CK20 in evaluating the efficacy of treatment and prognosis after surgery for colorectal cancer

Prediction of breast cancer metastasis risk using circulating tumor markers: A follow-up study

Epithelial‑mesenchymal transition was identified as a potential marker for breast cancer aggressiveness using reverse transcription‑quantitative polymerase chain reaction

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