Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization.

PURPOSE: Chromogenic in situ hybridization (CISH) is a new modification of the fluorescence in situ hybridization (FISH) technique for detection of oncogene amplification in archival tumor samples. In CISH, the oncogene probe is detected using a peroxidase reaction, allowing use of transmitted light microscopy. We compared detection of HER-2/neu amplification by CISH with a Food and Drug Administration-approved two-color FISH test in an interlaboratory setting. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 197 breast cancers were analyzed for HER-2 amplification by CISH. Two-color FISH (PathVysion) CISH of 17 centromere was done if the observer considered it necessary to ascertain amplification status in tumors with borderline HER-2 CISH copy numbers. RESULTS: Paired CISH/FISH results were available from 192 (97%) of 197 cases, no clear difference in success rates of either method was observed. Centromere 17 CISH was considered necessary in seven tumors. CISH and two-color FISH results were concordant in 180 cases (93.8%). There were 92 and 88 tumors found HER-2 amplified and nonamplified, respectively, by both methods. Eight tumors were amplified by CISH but not by FISH, and four tumors exhibited the opposite condition (kappa coefficient 0.875). In 7 of 12 cases differences between the two methods could have related to a lack of CISH chromosome 17 information. The remaining cases were explained by difficult histology (ductal carcinoma in situ, poor representativity, dense lymphocytic infiltration, or intratumoral heterogeneity). CONCLUSIONS: These results indicate that CISH could provide an accurate and practical alternative to FISH for clinical diagnosis of HER-2/neu oncogene amplification in archival formalin-fixed breast cancer samples.     

Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling.

PURPOSE: To develop a genome-based classification scheme for clear-cell sarcoma (CCS), also known as melanoma of soft parts (MSP), which would have implications for diagnosis and treatment. This tumor displays characteristic features of soft tissue sarcoma (STS), including deep soft tissue primary location and a characteristic translocation, t(12;22)(q13;q12), involving EWS and ATF1 genes. CCS/MSP also has typical melanoma features, including immunoreactivity for S100 and HMB45, pigmentation, MITF-M expression, and a propensity for regional lymph node metastases. MATERIALS AND METHODS: RNA samples from 21 cell lines and 60 pathologically confirmed cases of STS, melanoma, and CCS/MSP were examined using the U95A GeneChip (Affymetrix, Santa Clara, CA). Hierarchical cluster analysis, principal component analysis, and support vector machine (SVM) analysis exploited genomic correlations within the data to classify CCS/MSP. RESULTS: Unsupervised analyses demonstrated a clear distinction between STS and melanoma and, furthermore, showed that CCS/MSP cluster with the melanomas as a distinct group. A supervised SVM learning approach further validated this finding and provided a user-independent approach to diagnosis. Genes of interest that discriminate CCS/MSP included those encoding melanocyte differentiation antigens, MITF, SOX10, ERBB3, and FGFR1. CONCLUSION: Gene expression profiles support the classification of CCS/MSP as a distinct genomic subtype of melanoma. Analysis of these gene profiles using the SVM may be an important diagnostic tool. Genomic analysis identified potential targets for the development of therapeutic strategies in the treatment of this disease.     

Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.     

Pulmonary thrombo-embolism in nephrotic syndrome treated with tissue plasminogen activator

We describe the case of a boy with steroid sensitive nephrotic syndrome and left pulmonary artery thrombo-embolism. Clinical presentation initially suggested sepsis and respiratory signs were minor. Treatment with tissue plasminogen activator infused into the pulmonary artery was successful. Conclusion Pulmonary thrombo-embolism should be considered in unwell children with nephrotic syndrome. Received: 6 September 1996 / Accepted: 17 December 1996     

Haptoglobin-related protein as a serum marker in malignant lymphoma

A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin’s lymphoma (n=58) and Hodgkin’s disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430xl0³ u/ml, range 0-4000xl0³) were significantly higher than in the control group (median 68xl0³ u/ml, range 0-180xl0³) (p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), “B” symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma. This work is dedicated to the memory of Dr. Arie H. Bartal, a dedicated oncologist and friend. This work was supported by Chemotech Thechnologies Ltd., by grant no. 3676 from the Chief Scientist’s Office of the Ministry of Health, Israel, and by the Fund for Promotion of Research in the Technion.     

Prolonged focal application of polyethylene glycol induces conduction block in guinea pig spinal cord white matter.

A 2-min focal application of Polyethylene Glycol (PEG) to injured mammalian spinal cords can offer significant yet limited restoration of functional and structural integrity. However, longer application of PEG has not been tested in similar injuries. In this study, isolated spinal cord white matter strips from adult guinea pigs were subjected to a 25 min exposure of PEG (MW: 2000; 50% w/w), with or without prior compression. When applied in a continuous steam, PEG, with a delay of about 6 min, suppressed the compound action potential (CAP) amplitude to 64+/-4% of the pre-PEG level in uninjured cords and to 64+/-7% in compressed cord strips. Both recovered to 70+/-5% (uninjured) and 88+/-11% (compressed) of the pre-PEG level following wash. When PEG was applied in a pulsatile manner, no significant decrease of CAP amplitude was observed. In summary, our results show that focal continuous application of PEG has minimal toxicity if applied for less than 5 min. Pulsatile application could extend this duration to at least 25 min with no toxicity. This study could be useful in determining the optimal protocol for the use of PEG in both animal research and human spinal cord victims.     

Tuberculosis notifications in Australia, 2003.

The National Notifiable Disease Surveillance System (NNDSS) received 982 tuberculosis (TB) notifications in 2003, of which 947 were new cases, 33 were relapses and two were cases with unknown history. The incidence of TB in Australia has remained at a stable rate since 1985 and was 4.9 cases per 100,000 population in 2003. The high-incidence groups remain people born overseas and Indigenous Australians at 19.9 and 8.7 cases per 100,000 population, respectively. By contrast the incidence in non-Indigenous Australians was 0.9 per 100,000. Comparison of the 2003 TB notification data against the performance indicators set by National Tuberculosis Advisory Committee highlights that enhanced TB control measures should be considered among these high-risk groups.     

Measuring clients' satisfaction with self-help agencies

OBJECTIVE: Clients' satisfaction with their involvement in treatment decisions has been largely overlooked in the formulation of satisfaction measures. The authors describe the development of a scale that assesses clients' satisfaction with services and with their involvement in treatment decisions. METHODS: Long-term users of four client-operated mental health self-help agencies were interviewed at baseline (N=310) and six months (N=248) using the 11-item Self-Help Agency Satisfaction Scale (SHASS). The scale was developed on the basis of consumers' input about their satisfaction with services and their involvement in treatment decisions. To explore the relationship between satisfaction as measured by the SHASS and outcomes, the six-month interview included four outcome measures-independent and assisted social functioning, symptom severity, and a sense of personal empowerment. Internal consistency, stability, and discriminant validity were evaluated. RESULTS: Factor analyses confirmed that the SHASS has two subscales, one assessing service satisfaction and the other assessing satisfaction with involvement in treatment decisions. The scale and its subscales showed high internal consistency, moderate stability, and discriminant validity. The SHASS subscales showed modest associations with two of four outcome measures-assisted and independent social functioning. CONCLUSIONS: The SHASS is a brief instrument that can be used to measure clients' satisfaction with their involvement in treatment in mental health self-help agencies.