Serum HER2/ECD value in stage I and II early breast cancer: need of a lower cut-off?

BACKGROUND: HER2 overexpression is well-established risk factor of worse prognosis in metastatic and early breast cancer. HER2 positivity can be determined from tumor tissue by immunohistochemical staining or by fluorescent in situ hybridization, or from serum by measuring concentration of HER2 receptor extracellular domain (HER2/ECD). HER2/ECD correlates well with worse prognosis in metastatic and locally advanced (stage III) disease if serum concentration is >15 ng/ml, but there are no consistent data for patients with early breast cancer. METHODS AND RESULTS: 41 patients with stage I and II breast cancer and 52 healthy controls were included into the study. HER2/ECD was determined before surgery and correlated with HER2/neu overexpression, Ki67, hormone receptor status and disease stage, and compared with value in healthy controls. Mean serum HER2/ECD concentration in patients was 8.62 ng/ml and 5.78 ng/ml in controls, and the difference was statistically significant (p = 0.000061). The best diagnostic cut-off value was 7.7 ng/ml, with 76.92% sensitivity and 72.92% specificity. Positive predictive value of the test was 69.77% and negative predictive value was 79.55%, with 74.71% of patients correctly classified. Serum HER2/ECD correlated with hormone receptors status, and no correlation with histological overexpression has been observed. CONCLUSION. Serum HER2/ECD concentration of ≥7.7 ng/ml has possible diagnostic value in stage I and II breast cancer. It should not be used as a determinant of HER2 positivity. Prognostic significance of HER2/ECD in early breast cancer, its correlation with hormone receptor status, and interconnection between hormone receptors and HER2 receptor signaling should be further analyzed, since it may have therapeutic implications.

Lymph node, spleen and peripheral blood lymphocytes as stimulators of alloreactivity.

Before and after kidney transplantations, in vitro tests that measure the level of reactivity between donor and recipient lymphocytes are performed for better organ selection and as indicator of possible organ rejection. In these tests, donor's and recipient's lymphocytes are stimulated for proliferation, which intensity is measured and accordingly organ recipient reactivity towards graft is determined. Lymph node, spleen and peripheral blood lymphocytes are used for those purposes. For better interpretation of these in vitro tests it should be important to determine mitogenic ability of lymphocytes of different origin and to choose the most adequate cells. To compare mitogenic ability of deceased donor lymph node, spleen and peripheral blood lymphocytes one-way mixed lymphocyte culture (MLC) was used. As stimulators irradiated lymphocytes from spleen, lymph node and peripheral blood samples of 12 deceased donors were used while as responders lymphocytes from peripheral blood of healthy individuals, chosen according HLA-DRB1 alleles (stimulators and responders were HLA-DRB1 identical, semi-identical or different), were used. Spleen lymphocyte activity was the best with different cells and the weakest with identical cells. Impact of polyclonal mitogens (PHA - phytohemagglutinin, Con A - concanavalin A and PWM - pokeweed mitogen) on lymphocyte proliferation was tested on lymphocytes from spleen and lymph node of deceased donors. Results obtained in culture in vitro showed that spleen cells had exerted the best mitogenic potential and PHA had the greatest impact upon lymphocyte proliferation. This investigation is of importance for establishing the best model to reflect in vivo situation in transplanted patient.

[Primary cytomegalovirus infection after combined cadaveric transplantation of the liver and kidney]. / Primoinfekcija citomegalovirusom nakon kombinirane kadavericne transplantacije jetre i bubrega.

Seronegative transplant recipients are at a high risk of developing primary cytomegalovirus (CMV) infection. The D+/R--constellation produces a 60%-80% probability of CMV disease. In such cases CMV prophylaxis is justified. Presentation of a 12-year old boy who developed a primary CMV infection following A combined liver-kidney transplantation; evaluation of prophylactic options and review of some difficulties in the diagnosis of CMV infection. A cadaveric liver-kidney transplantation (Tx) was done in a 12-year old boy with ESRD due to type I primary hyperoxaluria. CMV status: D+, R-; number of mismatches: 5. PRA 0; kidney cold ischemia time (CIT): 13.54 h; liver CIT: 10.10 h; immediate diuresis; Immunosuppression protocol: anti IL-2 receptor antibodies, steroids, mycophenolate mofetil (MMF); cyclosporine introduced on day 6. Over the first week, daily hemodialyses were done in order to remove oxalate deposits. Kidney and liver biopsies: no ACR, no oxalate deposits. CMV prophylaxis with ganciclovir started on day 0. Routine serology and PCR for CMV follow-up showed: pp 65, IgM and IgG, CMV. DNA (Murex CMV. DNA Hybrid Capture test 2.0): negative over the first 3 months. Day 98: CMV pp 65 positive, IgM neg, DNA neg. Day 108: pp 65 neg, IgM positive, IgG neg. CMV. DNA positive (15 x 105 copies/ml). Clinical status: except for mild Cushing, liver tests and kidney function were normal. Ganciclovir was administered intravenously (i.v.) and after 14 days continued perorally. A few days later, leukopenia with severe neutropenia (neutrophil count: 400) and right otitis media developed. MMF and ganciclovir were withdrawn for a few days and reintroduced after WBC count reconstitution. We had no possibility to monitor MMF. Day 150 pp 65 neg, IgM still positive, IgG neg. No clinical signs of infection. Liver and kidney functions normal. After liver-kidney transplantation in a CMV high-risk pediatric patient (D+/R-), asymptomatic CMV primary infection developed. Although ganciclovir prophylaxis could not prevent the infection, it was mild and delayed. Due to bone marrow suppression, discontinuation of MMF and ganciclovir was necessary. Antigenemia assay pp 65 did not correlate very well with CMV viremia so it could not be recommended as a routine test. It should be used in combination with other CMV tests.