Comparative Study for the Determination of HER2 gene Amplification and Overexpression in Breast Cancer

PURPOSE: The human epidermal growth factor receptor-2 (HER2) is overexpressed in breast cancer. The subset of patients with breast cancer demonstrating a HER2-positive status has aggressive tumors and a poor prognosis. Knowledge of the HER2 status is prerequisite when considering a patient's eligibility for anti-HER2 targeted therapy (Herceptin(R)). There are several assays available for determining the HER2 status. The aim of this study was to compare and evaluate the HER2 status in breast cancer by means of immunohistochemistry (IHC), FISH and real-time PCR. METHODS: DNA samples from fresh tumor tissues of 20 patients with breast cancer were analyzed with real-time PCR, using the LightCycler-HER2/neu PCR assay. A tissue microarray, containing 20 samples obtained from formalin- fixed, paraffin-embedded tissues, was used for IHC and FISH (PathyVysionTM). RESULTS: The frequencies of HER2 gene amplification for real-time PCR and FISH were 35 and 65% respectively, and the IHC frequency of overexpression was 70%. This study showed 75% concordance between IHC vs. FISH, 65% between IHC vs real-time PCR and 70% between FISH vs. real-time PCR. Considering real-time PCR as the gold standard, this study showed sensitivities and specificities of 100 and 46.2% for IHC, and of 100% and 53.8% for FISH. CONCLUSION: These results demonstrated marked discordance for the HER2 stati according to the various methods used. IHC, a familiar cost-effective test, will undoubtedly remain in routine clinical practice for HER2 screening but confirmatory HER2 testing using either FISH or real-time PCR is recommended for indeterminate cases. Real-time quantitative PCR for HER2 appears to be clinically useful due to its simplicity and ability to produce rapid results.

Outcome Analysis after Treatment of Acute Limb Ischemia

PURPOSE: Acute limb ischemia is not only a limb-threatening but also a life-threatening condition. Despite the use of surgical and/or thrombolytic therapy for this urgent treatment -requiring condition, it is still reported to carry high morbidity and mortality rates. METHODS: We analyzed the treatment outcomes of 118 limbs (11 upper limbs, 107 lower limb) with acute limb ischemia treated for 103 patients (age, median: 64, male 89 female 14) at the Department of Surgery, Kyungpook National University Hospital, from March 1993 to March 1999. The underlying causes of acute limb ischemia included 62 limbs with acute arterial embolism in 51 patients, 39 limbs with acute arterial thrombosis in 37 patients, 15 limbs with graft occlusion in 14 patients, and 2 limbs of undetermined cause of limb ischemia in 1 patient. The retrospective, nonrandomized study was done. RESULTS: The underlying causes of acute limb ischemia were arterial embolism in 52.5%, arterial thrombosis in 33.1%, bypass graft occlusion 12.7%, and undetermined cause in 1.7%. Severity of ischemia according to the SVS/ISCVS classification, 107 limbs (90.7%) were classified as category II and 9 limbs (7.6%) were in category III. For the limbs with embolisms, 47 embolectomies (including 6 cases treated with adjuvant thrombolytic therapy) and 10 arterial bypasses were performed. For the limbs with thromboses, 23 arterial bypasses, 5 thrombectomies, and 4 catheter directed thrombolytic therapies were performed. For the patients with acute graft occusion, 8 redo bypasses, 4 thrombolytic therapies, and 2 thrombectomies were performed. We experienced major limb amputations in 8.1%, hospital mortality in 13.7% and recurrence of ischemic symptoms in 16.1% during the follow-up period in the embolism patients and limb amputations in 2.7%, hospital mortality in 14.3%, and recurrence of ischemic symptoms in 8.3% of the thrombosis patients. Of the patients with category II ischemia, major limb amputation and hospital mortality rates were 4.7% and 9.2%, respectively. CONCLUSION: In dealing with acute limb ischemia, prompt and appropriate selection of treatment modalities, if needed in combined modes, is critically important in improving the treatment outcomes.