As well as the LMP2 DNA LMP 2A and Integrin Expression ALFA 6 as markers Progressivity Nasopharyngeal Cancer
ABSTRACT: Background: Cancer registry data from 2000 to 2005 in Dharmais Cancer Hospital (DCH) showed that most patients (56%) with nasopharyngeal cancer (NPC) already presented with distant metastases, especially in stadium IV. Thus, markers that are sensitive and specific to monitor the progression of NPC are necessary in the management of NPC cases. LMP2-DNA, LMP2A-RNA and ITG-alpha-6 protein are promising markers, which needed validation. Aim: To evaluate circulating LMP2-DNA, LMP2A-RNA and ITG-alpha-6 protein as markers of progression in NPC. Method: This was a cross sectional observational study. Subjects were patients newly diagnosed with NPC based on clinical, imaging and histopathologic findings. Staging was based on UICC 2002 TNM classification. Forty-six NPC patients who came to the DCH ENT Polyclinic were included in this study, and were divided into 2 groups: early stage (Stage I and stage II) and advanced stage (Stage III and IV). We collected whole blood anticoagulated with EDTA for determination of circulating LMP2-DNA, LMP2A-RNA and epithelial cell ITG-alpha-6 protein. Circulating LMP2-DNA and LMP2A-RNA assay was performed using real-time PCR and epithelial cell ITG-alpha-6 protein was measured by flowcytometry. Statistical analysis was performed to determine the correlation between independent (i.e. early stage vs advanced stage NPC) and dependent variable (i.e. LMP2-DNA, LMP2A-RNA and epithelial cell ITG-alpha-6 protein). Normality of data distribution was tested with Shapiro-Wilk test and statistical difference by Mann-Whitney test. Result: Of the 46 subjects, most were male (72%). Age of subjects ranged between 21 and 69 years. Age mean for male is 47 years (median : 48 years) and for women 44 years (median : 45 years). Histopathologic analysis of all subjects showed nonkeratinizing nasopharyngeal Ca undifferentiated subtype. Based on clinical staging, there were 17 (37%) patients in stage II, 14 (30%) in stage III, and 15 (33%) in stage IV. In each stage, the number of male subjects were more than female. LMP2-DNA level in early stage was significantly different from advanced stage (p=0.045). With a cut-off value of 56.40, sensitivity of the test was 72.41%, specificity 64.71%, PPV 77.78 % and NPV 57.89% (x2=0.014; OR=1.85). LMP2A-RNA level showed no significant difference between early stage and advanced stage (p=0.380). With a cut-off value of 56.55, sensitivity of the test was 64.30%, specificity 52.94%, PPV 70.37% and NPV 47.37% (x2= 0.220; OR= 1.34). Epithelial cell ITG-alpha-6 protein between the 2 groups did not show significant difference (p=0.625). With a cut-off value of 0.27, sensitivity was 72.40%, specificity 41.20%, PPV 67.72%, NPV 46.67% (x2= 0.343; OR= 1.27). Conclusion: LMP2-DNA may be used to predict progression. With a cut-off value of 56,40, LMP2-DNA showed good sensitivity, specificity and PPV. LMP2A-RNA may be used to predict progression though statistically showed no signifinant difference between early and advance stage. LMP2A RNA showed expression with a cut-off value of 56,55, and showed good sensitivity, specificity and PPV. Epithelial cell ITG-alpha-6 protein may be used to predict progression though statistically showed no signifinant difference between early and advance stage. In this study, epithelial cell ITG-alpha-6 protein showed expression with a cut-off value of 0,27% and showed good sensitivity, specificity and PPV.
ABSTRACT: Background: Cancer registry data from 2000 to 2005 in Dharmais Cancer Hospital (DCH) showed that most patients (56%) with nasopharyngeal cancer (NPC) already presented with distant metastases, especially in stadium IV. Thus, markers that are sensitive and specific to monitor the progression of NPC are necessary in the management of NPC cases. LMP2-DNA, LMP2A-RNA and ITG-alpha-6 protein are promising markers, which needed validation. Aim: To evaluate circulating LMP2-DNA, LMP2A-RNA and ITG-alpha-6 protein as markers of progression in NPC. Method: This was a cross sectional observational study. Subjects were patients newly diagnosed with NPC based on clinical, imaging and histopathologic findings. Staging was based on UICC 2002 TNM classification. Forty-six NPC patients who came to the DCH ENT Polyclinic were included in this study, and were divided into 2 groups: early stage (Stage I and stage II) and advanced stage (Stage III and IV). We collected whole blood anticoagulated with EDTA for determination of circulating LMP2-DNA, LMP2A-RNA and epithelial cell ITG-alpha-6 protein. Circulating LMP2-DNA and LMP2A-RNA assay was performed using real-time PCR and epithelial cell ITG-alpha-6 protein was measured by flowcytometry. Statistical analysis was performed to determine the correlation between independent (i.e. early stage vs advanced stage NPC) and dependent variable (i.e. LMP2-DNA, LMP2A-RNA and epithelial cell ITG-alpha-6 protein). Normality of data distribution was tested with Shapiro-Wilk test and statistical difference by Mann-Whitney test. Result: Of the 46 subjects, most were male (72%). Age of subjects ranged between 21 and 69 years. Age mean for male is 47 years (median : 48 years) and for women 44 years (median : 45 years). Histopathologic analysis of all subjects showed nonkeratinizing nasopharyngeal Ca undifferentiated subtype. Based on clinical staging, there were 17 (37%) patients in stage II, 14 (30%) in stage III, and 15 (33%) in stage IV. In each stage, the number of male subjects were more than female. LMP2-DNA level in early stage was significantly different from advanced stage (p=0.045). With a cut-off value of 56.40, sensitivity of the test was 72.41%, specificity 64.71%, PPV 77.78 % and NPV 57.89% (x2=0.014; OR=1.85). LMP2A-RNA level showed no significant difference between early stage and advanced stage (p=0.380). With a cut-off value of 56.55, sensitivity of the test was 64.30%, specificity 52.94%, PPV 70.37% and NPV 47.37% (x2= 0.220; OR= 1.34). Epithelial cell ITG-alpha-6 protein between the 2 groups did not show significant difference (p=0.625). With a cut-off value of 0.27, sensitivity was 72.40%, specificity 41.20%, PPV 67.72%, NPV 46.67% (x2= 0.343; OR= 1.27). Conclusion: LMP2-DNA may be used to predict progression. With a cut-off value of 56,40, LMP2-DNA showed good sensitivity, specificity and PPV. LMP2A-RNA may be used to predict progression though statistically showed no signifinant difference between early and advance stage. LMP2A RNA showed expression with a cut-off value of 56,55, and showed good sensitivity, specificity and PPV. Epithelial cell ITG-alpha-6 protein may be used to predict progression though statistically showed no signifinant difference between early and advance stage. In this study, epithelial cell ITG-alpha-6 protein showed expression with a cut-off value of 0,27% and showed good sensitivity, specificity and PPV.
