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Expression and Clinical Significance of cytokeratin-19 and Thymidine Kinase-1 in Advanced Gastrointestinal Cancer

Chinese Medical Journal 2016年第18期129卷 2168-2172页

作者： Ying-Ying Du Qiu-Jun Zhang Guo-Ping Sun Department of Oncology The First Affiliated Hospital of Anhui Medical University Hefei Anhui 230022 China

Background： As the clinical value of cytokeratin-19 （CK 19） and thymidine kinase-1 （TK1 ） in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease. Methods： A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK 19 was detected using quantitative real-time reverse transcription-polymerase chain reaction （PCR） in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival （OS） time. Results： Positive CKl 9 mRNA expression was detected in 74 （43.3%） of the 171 patients and positive TK1 expression was detected in 66 （68.8%） of the 96 patients. Furthermore, of the 96 patients, 36 （37.5%） were positive for both TK1 protein and CK19 mRNA, 30 （31.3%） were negative for TK1 protein, and 15 （15.6%） were negative for TKl protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK 19 mRNA expression had significantly shorter OS times than those who were negative for it （median OS 7.7 vs. 9.7 months, respectively; P = 0.02）. Moreover, patients who were positive tbr CK 19 mRNA and TK 1 protein expression had shorter OS times （median OS 6.1 months） than those who were positive for CKl9 mRNA and negative for TKl protein expression （median OS 9.1 months; P： 0.028）. Positive CK 19 mRNA expression was significantly associated with shorter OS in the univariate analysis （P = 0.027）. Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression （P = 0.024） was an independent predictor for OS in gastrointestinal cancer patients. Conclusions： Our results suggest that positive expression ofCKl9 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CKl9 and

关键词： Advanced Gastrointestinal Cancer cytokeratin-19 Overall Survival Thymidine Kinase-1

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Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood,bone marrow and peritoneal lavage of pancreatic carcinoma patients

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World Journal of Gastroenterology 2007年第2期13卷 257-263页

作者： Katrin Hoffmann Christiane Kerner Wolfgang Wilfert Marc Mueller Joachim Thiery Johann Hauss Helmut Witzigmann Department of Visceral Transplantation Thoracic and Vascular Surgery University of Leipzig Germany Institute of Laboratory Medicine Clinical Chemistry and Molecular Diagnostics University of Leipzig Germany

AIM： To evaluate the diagnostic potential of cytokeratin-19 （CK-19） mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas. METHODS： Sixty-eight patients with pancreatic cancer （/7 = 37）, chronic pancreatitis （n = 16）, and non-pancreatic benign surgical diseases （/7 = 15, control group） were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR. RESULTS： CK-19 mRNA expression was increased in 24 （64%） blood samples and 11 （30%） of the peritoneal lavage samples in the patients with pancreatic cancer. In 15 （40%） of the patients with pancreatic cancer, disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors （G2/G3）. Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancer patients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis. CONCLUSION： Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinorna by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.

关键词： Tumor cell dissemination Pancreatic cancer cytokeratin-19

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甲状腺乳头状癌细针穿刺涂片中Galectin-3、cytokeratin-19的表达及其临床意义

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实用癌症杂志 2019年第1期34卷 50-54页

作者：龙兆博张苗司婷婷张进秦娟陕西省宝鸡市人民医院 721000

目的探讨甲状腺乳头状癌(PTC)细针穿刺涂片中Galectin-3、cytokeratin-19的表达及其临床意义。方法选择甲状腺组织样本120例,其中正常甲状腺组织90例(对照组),PTC组织30例(观察组)。采用细针穿刺涂片法获得样本,使用免疫组化分析Galecti... 详细信息

目的探讨甲状腺乳头状癌(PTC)细针穿刺涂片中Galectin-3、cytokeratin-19的表达及其临床意义。方法选择甲状腺组织样本120例,其中正常甲状腺组织90例(对照组),PTC组织30例(观察组)。采用细针穿刺涂片法获得样本,使用免疫组化分析Galectin-3、cytokeratin-19中的表达情况,并进行相关性与危险因素分析。结果 Galectin-3、cytokeratin-19在对照组的阳性表达率为15.6%和4.4%,在观察组中的阳性表达率为80.0%和90.0%,观察组都高于对照组(P cytokeratin-19在PTC组织中的阳性表达率与PTC的病理分期、分化程度、淋巴结转移明显相关(P cytokeratin-19阳性表达的独立危险因素(P cytokeratin-19的阳性表达呈明显相关性(γ=0.607,P cytokeratin-19在PTC组织中呈现高表达状况,与PTC组织的病理分期、分化程度、淋巴结转移明显相关,可作为判断PTC患者病情的重要指标。

关键词： Galectin-3 cytokeratin-19 甲状腺乳头状癌细针穿刺涂片免疫组化

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A versatile method for enumeration and characterization of circulating tumour cells from patients with breast cancer

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Journal of Cancer Metastasis and Treatment 2017年第1期3卷 23-33页

作者： Ujjwala M.Warawdekar Vani Parmar Aruna Prabhu Abhay Kulkarni Meenal Chaudhari Rajendra A.Badwe CRI Lab Advanced Centre for Treatment Research and Education in Cancer(ACTREC)Tata Memorial CentreNavi Mumbai 410208India Department of Surgery Breast UnitTata Memorial HospitalTata Memorial CentreParelMumbai 400012India Homi Bhabha National Institute Anushakti NagarMumbai 400085India.

Aim:To establish a standardized protocol for the isolation and enumeration of circulating tumor cells(CTCs)from peripheral blood of patients with metastatic breast ***:The protocol used tumor cells spiked in a lymphoid cell line with detection by flow cytometry and quantitative reverse transcription polymerase chain reaction(QRT-PCR).Cells of the human mammary cancer subtypes were spiked into Jurkat cells,which served as the lymphocyte designate in numbers from 10 to 500 per 105 Jurkat *** mixed population was probed for CD45,EpCAM,and pancytokeratin acquired from flow cytometry and characterized by ***-PCR was done for CK-19,MUC-1,EpCAM,and *** was attained with blood samples from 22 patients with metastatic breast cancer and 20 healthy ***:Flow cytometry could detect 1 breast cancer cell per 100,000 Jurkat cells,with similar detection levels in the breast cancer *** from patients with breast cancer showed a range of CTCs from 1-85 per 10 mL of *** of expression for EpCAM,CK-19,Muc-1,and Her2neu confirmed the presence of CTCs in 76%of ***:Density gradient and immunomagnetic enrichment accomplished isolation of CTCs and quantitation was achieved using flow *** QRT-PCR and imaging further validated these findings,rendering a robust methodology.

关键词： Circulating tumor cells cytokeratin-19 flow cytometry circulating tumor cell enumeration quantitative reverse transcription polymerase chain reaction EpCAM

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