Current perspectives on HER2 testing: a review of national testing guidelines.

Knowledge of HER2 status is a prerequisite when considering a patient's eligibility for Herceptin (trastuzumab) therapy. Accurate assessment of HER2 status is essential to ensure that all patients who may benefit from Herceptin are correctly identified. There are several assays available to determine HER2 status: the most common in routine clinical practice are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Various factors can affect the results achieved with these assays, including the assay antibody/probe, the methodology and the experience of personnel. Many countries have implemented national testing guidelines in an attempt to standardize testing procedures and make results more accurate. These guidelines vary in the level of detail and the number of recommendations. This review looks at areas of consensus between the different national testing guidelines and highlights where errors may arise during the testing procedure. The key point underlined by this review is that whatever method is used to test for HER2 status, the technology must be validated first, and there must be regular internal and external quality control and quality assurance procedures.     

Malignant lymphoma of the stomach in association with inflammatory myofibroblastic tumor of the spleen. A case report

We report on a case of a 40-year-old male patient who underwent a gastrectomy because of a biopsy-proven large B-cell lymphoma of the stomach. On surgery, a nodule in the spleen also was noted. Grossly and microscopically, the two lesions were different: the tumor of the stomach appeared white-gray on the cut surface and was a centroblastic variant of diffuse large B-cell lymphoma. Histologically, one perigastric lymph node was involved. Grossly, the splenic nodule was gray-yellow and had a histological appearance of an inflammatory myofibroblastic tumor (IMT). The association between malignant tumor and IMT is rare. In such an association, the latter lesion most often has been reported in the spleen. As EBV may be involved in the genesis of both lymphoma and IMT, we tested both lesions for its presence using in situ hybridization, but the tests were negative. It remains to be verified whether the association between lymphoma and IMT is more than fortuitous.     

Trends in primary care consultations for asthma in Switzerland, 1989-2002

BACKGROUND: There is widespread debate about trends in the occurrence of asthma in industrialized countries. This study was conducted to investigate time trends in consultations for asthma in primary care in Switzerland. METHODS: Prospective observational study from 1989 to 2002 within the Swiss Sentinel Surveillance Network; a primary care surveillance system. We used time series analysis and non-parametric smoothing methods to investigate long-term and short-term trends in rates of asthma episodes per 1000 consultations. From 1994 to 2002 we compared rates of first episodes with all subsequent consultations for asthma. RESULTS: Overall consultation rates for asthma per 1000 primary care consultations increased from 1989 to 1994 then stabilized and have declined since 2000. Long-term trends showed a small decline in first consultations for asthma from an average of 0.78 (95% credibility intervals (CI) 0.74-0.81) in 1999 to 0.62 (95% CI 0.55-0.69) per 1000 consultations in 2002. Subsequent consultations for asthma have been declining since at least 1994, from an average of 1.5 (95% CI 1.40-1.61) per 1000 consultations in 1994 to 0.93 (95% CI 0.82-1.04) in 2002. In addition, the ratio of subsequent to first episodes of asthma fell in all age groups. CONCLUSIONS: In Switzerland, primary care consultations for asthma, subsequent to the initial diagnosis, have been declining since 1994. This is more likely to be owing to an increase in the use of home medication than to a shift in care to hospital settings. The incidence of diagnosed asthma might also be decreasing.     

Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse

Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and then a 4-week-rest period) is consistently deteriorating throughout next 14 days, if not reversed or ameliorated by therapy (/kg per day): a stable gastric pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 microg, 10 ng), losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of therapy and clinical status (hypotension, increased heart rate and respiratory rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited additionally increased BET-1 and aggravated clinical status, while enzyme values maintained their initial increase. BPC157 (10 microg/kg) and amlodipine treatment reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1 (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10 ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is accordingly improved by the BPC157 regimens and amlodipine.     

Genotype phenotype correlation in a pediatric population with antithrombin deficiency

Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases.

Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.

Pathobiologic identification of two distinct breast carcinoma subsets with diverging clinical behaviors

Many different pathological and biological variables which characterize breast carcinomas have been found to be associated. The aim of this work was to analyze the complex relationship among these parameters. The pathologic, biologic, and clinical characteristics of a series of primary breast carcinomas from 676 patients were retrospectively investigated. Multiple correspondence analysis of 13 factors revealed clustering of eight pathobiologic variables, that is histologic grade, necrosis, lymphoid infiltration, number of mitoses, cerbB2 overexpression, p53, progesterone receptor, and bcl2 expression. An index for each tumor calculated on the basis of these eight factors served to distinguish two different tumor phenotypes, designated A and B. Phenotype A is represented by tumors sharing most of the biologic features of normal breast tissues: indeed, these tumors are characterized by a relatively high degree of differentiation, low proliferation, no necrosis or leukocyte infiltration, and no gene alterations. By contrast, phenotype B is quite divergent from the normal tissue because of its poor differentiation, high proliferation, frequent gene alterations and evidence of a host immune reaction. As regards the disease progression, these two subsets showed marked differences: phenotype A tumors had a low recurrence rate per year that remained constant over time and affected more frequently elderly patients, whereas group B tumors showed high aggressivity in the first years after surgery followed by a low longterm recurrence rate and were more frequently seen in younger patients. These data suggest that breast carcinoma consists of two different subsets that can be identified on the basis of pathobiologic features.