Signaling pathways in early onset sporadic breast cancer of patients in Indonesia.

AIM: to determine signaling pathways in breast cancers from patients aged 35 years old or younger and patients aged more than 35 years old. METHODS: this was a cross-sectional, comparative study of female breast cancer patients who were recruited and divided into two age groups, i.e. 35 years or younger and more than 35 years old. Specimens were obtained by biopsy or surgical removal of the tumors and were confirmed by histopathological examination. The expression of ER, IGF-1R, Her-2, MAPK, and cyclin D1 were measured using immunohistochemistry. RESULTS: ninety-three patients were recruited from September 2004 to December 2005. Forty-three patients were 35 years or younger. More than 90% of the patients within the two groups showed invasive ductal carcinomas and more than half of these tumors were grade 2. Immunohistochemical staining was successfully done in 90 patients. ER-alpha expression was negative in 33 breast cancers (78.6%) from patients less than 35 years old and 32 cancers (66.7%) of older patients. The expressions of IGF-1R, Her-2, MAPK, and cyclin D1 were positive, respectively in 17 (40.5%), 11 (26.2%), 28 (66.7%), and 7 (16.7%) cancers within the group of patients 35 years old or younger, and, respectively in 18 (37.5%), 11 (22.9%), 37 (77.1%), and 9 (18.8%) of cancers from patients more than 35 years old. CONCLUSION: there were no statistically significant differences in the expression of any of the biomarkers between the two groups. In all patients, ER was negative in 72.2% cases and MAPK was positive in 76.7% cases. Patients aged 35 years or younger showed similar ER, IGF-1R, Her-2, MAPK, and cyclin D1 expressions compared to cancers from patients more than 35 years old. These were predominantly ER-negative, suggesting that estrogen does not play a dominant role in their growth. The frequent expression of MAPK in these cancers raises the possibility that growth factors play a dominant role in their growth.

Cut-off levels based on deviation from standard negative control is better than moderate level based on fixed cut-off for ACA assessed using ELISA for the diagnosis of antiphospholipid syndrome.

AIM: To assess the consistency of the standard negative control of IgG and IgM ACA levels within runs and batches of tests, and levels of ACA agreement between those established according to deviation from standard negative control and those established based on a fixed level cut off. METHODS: Serum samples of 148 patients who presented an INR < 0.9 or prothrombin activity of > 130% or aPTT below 0.8 times control or thrombosis with aPTT below 1.2 times control were tested in a 22-time running test to determine IgG and IgM ACA levels using Quanta Lite ACA IgG (HRP) and Quanta Lite ACA IgM (HRP) commercial reagents. RESULTS: Coefficients of variant within runs and batches of standard negative control IgG and IgM ACA levels were 19.30% and 29.17% respectively. Using kappa statistics to determine degree of agreement between cut-off levels by deviation from standard negative control and fixed cut-off level of ACA identified using ELISA, the disagreement in IgM and IgG were k 0.30, and 95% CI of k 0.27 to 0.34 (z = 1.033, p = 0.3015), and k 0.63, and 95% CI of k 0.53 to 0.73 (z = 1.411, p = 0.1584) for cut-off levels based on deviations from standard negative control and fixed cut-off levels respectively. Cut-off levels based on deviation from standard negative control was more sensitive, with a 92% predictive true positive value, compared to a 69% predictive true positive value by fixed cut-off levels of IgM ACA detected using ELISA, and nearly equivalent to IgG ACA, with 84.4% and 87.1% predictive true positive values respectively. CONCLUSION: Cut-off points based on fixed levels of ACA detected using ELISA cannot be applied, because both IgG and IgM ACA levels of standard negative control were inconsistent among runs and batches. Cut-off points based on the deviation of 3 standard negative control levels for IgG ACA and based on deviations of 2.5 times from standard negative control levels for IgM ACA were better than cut off by fixed levels of ACA in producing true positive results.