Expression Of TK1in Human Breast Cancerand Its Clinical Significance

BACKGROUND AND OBJECTIVE: The position of thymidinekinase1(TK1) expression during cell division is in the cytoplasm. It is acatalytic enzyme to convert deoxythymidine into thymidylate. It is the keyenzyme of pyrimidine salvage pathway. The aim of this study was to evaluatethe expression of thimidine kinase1in serum and tissue of patient with breastcancer, and to analyzes the correlationship of TK1with the clinicalpathological characteristics，CEA，CA153，ER，PR，Her-2，MIB-1andImaging BI-RADS category. To explore the correlationship with breast tumorbiological behavior. And further analysis the use of serum TK1in breastcancer diagnosis, treatment, prognosis.PATIENTS AND METHORD: Chemiluminesence dot blot assay wasused to detect TK1in serum of145breast cancer patients and55patientswith breast fibroadenoma. mmunohistochemistry was used to detect TK1in tissue of40breast cancer patients and10patients with breast fibroadenoma.Meanwhile the concentration of serum CEA and CA153had also beendetermined. ER、PR、HER-2、MIB-1expression was also dectected in145breast cancer tissue. The relation between serum TK1and clinicalpathological characteristics、ER、PR、HER-2、MIB-1status was analyzed.Collect the imaging findings of200patients,including breast ultrasound,breast mammography, and breast magnetic resonance. The relationshipbetween TK1and BI-RADS category was discussed.RESULTS: TK1expression in tissue of breast cancer was77.5%. It washigher than that of fibroadenoma (40%). Tissue TK1expression waspositively correlated with serum TK1expression(P=0.036). Theconcentration of TK1in serum of breast cancer patients was2.749±0.1215pM. It was significantly higher than in patients with breastfibroadenoma (P<0.0001). Serum TK1levels were statistically increased inpatients with lymph node metastasis (P=0.049), distal metastasis (P=0.0031),and late TNM stage(P=0.01). No serum TK1level differences were found inpatients with different ages (P>0.05), different tumor grades (P=0.453) anddifferent tumor size (P=0.908).The concentration of TK1in serum of ER+cases was no higher thanthat in ER-cases with breast cancer(P=0.726). Serum TK1level was no relation with PR(P=0.212), Her-2(P=0.272),MIB-1(P=0.142).There is no correlation between serum TK1and CEA, CA153. SerumTK1sensitivity=79.3%, specificity=90.9%, diagnostic accuracy=82.5%. Itwas much higher than CEA (sensitivity=11.43%, specificity=73.24%,diagnostic accuracy=43.24%) and CA153(sensitivity=20.51%,specificity=94.45%, diagnostic accuracy=46.22%). The expression of CEA,CA153is not different in between benign and malignant tumors.We studied the serum TK1level and preoperative imaging results of twohundred patients with breast tumor. Ultrasound assessment category isBI-RADS system. We found,the serum TK1level of BI-RADS category4C-6was significantly higher than that of category0-4B(P<0.001). Thecombined detection of serum TK1and ultrasound could improve thediagnostic yield. Consistently, the serum TK1levels in patients with MRBI-RADS categories4C-6were higher than categories0-4B (P=0.032). Theserum TK1levels in patients with mammography BI-RADS categories4C-6were higher than categories0-4B (P=0.002). Meanwhile, the combineddetection of serum TK1and ultrasound/MRI improved the diagnostic yield.Our study was conducted on2years follow-up of these patients. To theend of the follow-up period,200patients were all alive. There were fivepatients had disease progression. A benign tumor patient progressed to invasive breast cancer in two years later （TK1=6.67pM）. Four cases weremalignant tumor. One patient was found contralateral breast cancer ineighteen months later（TK1为3.72pM）. The other three patients appeareddistant metastasis later（TK1=5.42，4.91，2.04pM）. These cases’TK1levelwas higher. The PFS of all200patients was not significantly different(P=0.564).CONCLUSION: Serum and tissue TK1expression of breast cancerpatients is significantly increased, and is in correlation with lymph nodemetastasis and tumor stage. The diagnostic accuracy of serum TK1is higherthan CEA, CA153. The serum TK1expression is related with BI-RADScategory of imaging description. The combined detection of serum TK1andimaging tests improved the diagnostic yield. TK1test might be a potentialtool for screening, prognosis determination and effect evaluations of targetedtherapy in breast carcinoma.