An evaluation of immunoreactivity for c-erbB-2 protein as a marker of poor short-term prognosis in breast cancer.

Eighty-five breast carcinomas from the same number of patients have been assessed immunohistochemically using the antiserum 21N for the presence of the c-erbB-2 protein. Twenty-two of the patients had evidence of advanced disease (tumour fixation or distant metastases) at presentation. Follow-up was for a median of 24 months. c-erbB-2 protein was detected in the majority of cells in 14 (16.5%) carcinomas, and to a lesser extent in a further six (7%) tumours. There was no relationship between staining and stage, node status or size but more poorly differentiated carcinomas had evidence of staining (36%) than well (17%) or moderately (14%) differentiated carcinomas (P = 0.02). There was a significant association between staining and mortality (P = 0.009) and recurrence (P = 0.0002). The relative risk of death for staining compared to no staining (after adjusting for node status, stage and grade) was 2.97 (95% confidence interval 1.29, 6.84) and the relative risk of recurrence for staining compared to no staining after similar adjustment was 3.85 (95% confidence interval 1.86-7.97). In this particular group of patients immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis

The Effects of Age-of-Acquisition on Ambiguity Resolution: Evidence from Eye Movements

Words that are rated as acquired earlier in life receive shorter fixation durations than later acquired words, even when word frequency is adequately controlled (Juhasz & Rayner, 2003; 2006). Some theories posit that age-of-acquisition (AoA) affects the semantic representation of words (e.g., Steyvers & Tenenbaum, 2005), while others suggest that AoA should have an influence at multiple levels in the mental lexicon (e.g. Ellis & Lambon Ralph, 2000). In past studies, early and late AoA words have differed from each other in orthography, phonology, and meaning, making it difficult to localize the influence of AoA. Two experiments are reported which examined the locus of AoA effects in reading. Both experiments used balanced ambiguous words which have two equally-frequent meanings acquired at different times (e.g. pot, tick). In Experiment 1, sentence context supporting either the early- or late-acquired meaning was presented prior to the ambiguous word; in Experiment 2, disambiguating context was presented after the ambiguous word. When prior context disambiguated the ambiguous word, meaning AoA influenced the processing of the target word. However, when disambiguating sentence context followed the ambiguous word, meaning frequency was the more important variable and no effect of meaning AoA was observed. These results, when combined with the past results of Juhasz and Rayner (2003; 2006) suggest that AoA influences access to multiple levels of representation in the mental lexicon. The results also have implications for theories of lexical ambiguity resolution, as they suggest that variables other than meaning frequency and context can influence resolution of noun-noun ambiguities

The Effects of Age-of-Acquisition on Ambiguity Resolution: Evidence from Eye Movements

Words that are rated as acquired earlier in life receive shorter fixation durations than later acquired words, even when word frequency is adequately controlled (Juhasz & Rayner, 2003; 2006). Some theories posit that age-of-acquisition (AoA) affects the semantic representation of words (e.g., Steyvers & Tenenbaum, 2005), while others suggest that AoA should have an influence at multiple levels in the mental lexicon (e.g. Ellis & Lambon Ralph, 2000). In past studies, early and late AoA words have differed from each other in orthography, phonology, and meaning, making it difficult to localize the influence of AoA. Two experiments are reported which examined the locus of AoA effects in reading. Both experiments used balanced ambiguous words which have two equally-frequent meanings acquired at different times (e.g. pot, tick). In Experiment 1, sentence context supporting either the early- or late-acquired meaning was presented prior to the ambiguous word; in Experiment 2, disambiguating context was presented after the ambiguous word. When prior context disambiguated the ambiguous word, meaning AoA influenced the processing of the target word. However, when disambiguating sentence context followed the ambiguous word, meaning frequency was the more important variable and no effect of meaning AoA was observed. These results, when combined with the past results of Juhasz and Rayner (2003; 2006) suggest that AoA influences access to multiple levels of representation in the mental lexicon. The results also have implications for theories of lexical ambiguity resolution, as they suggest that variables other than meaning frequency and context can influence resolution of noun-noun ambiguities

Recommendations for HER2 testing in the UK

Determining the HER2 status of breast carcinomas is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin(R)), which has recently been licensed for the treatment of metastatic disease. This necessitates a test based on archival material. The preferred analyses are immunohistochemistry with fluorescent in situ hybridisation (FISH) as a follow up test for ambiguous results. Guidelines have been developed for standardised, well controlled procedures for the provision of reliable results. A group of three reference laboratories has been established to provide advice, quality assurance, and materials, where needed

Psoriatic disease and body composition : a systematic review and narrative synthesis

Background Obesity is a leading comorbidity in psoriatic disease, including both psoriasis (PsO) and psoriatic arthritis (PsA), and is associated with adverse metabolic and cardiovascular (CV) outcomes. Anthropometric parameters, such as weight, body mass index (BMI) and waist-to-hip ratio, have been extensively reported in psoriatic disease. However, the associations of body composition and fat distribution with psoriasis have not yet been fully defined. Objectives To identify whether patients with psoriatic disease, including psoriatic arthritis, have altered body composition compared with the general population, and to review existing modalities for the assessment of body composition. Methods Electronic searches of the literature were conducted in PubMed, Medline (Ovid®), Embase (Ovid®), Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria. The research question was answered with a systematic literature review and results were summarized narratively. Results Twenty-five full text articles met the inclusion criteria and were included in the final narrative analysis. The studies were of heterogeneous design and used a range of objective measures to assess body composition, including simple anthropometric measures, bioimpedance analysis (BIA), dual energy X-ray absorptiometry (DXA) and computed tomography (CT). Few studies met all the quality assessment criteria. Clinical heterogeneity prevented meta-analysis. Conclusions Patients with psoriatic disease reveal defined body composition changes that are independent of obesity and the customary metabolic syndrome, including higher overall body fat, visceral fat and sarcopenia. These findings emphasize that patients with psoriatic disease should be screened for abnormal adipose effects beyond their weight and body mass index (BMI). Our findings show that the last decade has seen an exciting expansion of research interest in the development and validation of new modalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group; hence there is a need for validation of existing modalities and standardization of assessment tools

Evaluation of epidermal growth factor receptors in bladder tumours.

Epidermal growth factor (EGF) receptor expression in 31 primary human bladder tumours was quantitated using both structural and functional assays and the EGF receptor gene in the same tumours was analyzed by Southern blot analysis. Immunocytochemical studies using the EGFR1 monoclonal antibody (Mab) showed a significant correlation between EGF receptor levels and the stage and grade of the tumours. Autophosphorylation assays employed to evaluate the receptor's tyrosine kinase activity gave results which in general were consistent with the immunocytochemical data. Using internally controlled immunocytochemical studies with two Mabs and Southern blot analysis of DNA isolated from the tumours, no evidence was obtained for the production of truncated receptors similar to those encoded by the v-erb-B oncogene. Gene amplification was not found in any of the superficial tumours, but one invasive tumour with high EGF receptor expression had an 8-10 fold amplification of the EGF receptor gene. The EGF receptor isolated from this tumour showed a normal pattern of tyrosine phosphorylation at all three major autophosphorylation sites. Our detailed study is consistent with the correlation previously found between EGF receptor expression and stage and grade of bladder tumours, and suggests that at this level of analysis EGF receptors in bladder tumours are not abnormal in structure or size, autophosphorylation activity, or gene structure

c-erbB-2 expression in benign and malignant breast disease.

An antibody, 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein has been used immunocytochemically in a retrospective study of formalin fixed paraffin embedded breast biopsies. Fourteen out of 103 infiltrating ductal carcinomas exhibited positive membrane staining. Fifty-four of these tumours had lymph node involvement of which nine contained stained cells. These were all cases where the primary tumour was positive. In this series there was no correlation between c-erbB-2 overexpression and lymph node status. In five of the positive cases studied there was an associated in situ component which was also positively stained. Ten out of 24 pure intraduct carcinomas showed membrane staining, but none of the 149 benign conditions studied, which included 22 radial scars and 13 cases of atypical ductal proliferation, demonstrated the pattern of staining associated with overexpression. It is concluded that the c-erbB-2 protein is overexpressed in a minority (approximately 14%) of infiltrating ductal carcinomas and only in cells that are cytologically malignant. Overexpression of c-erbB-2 is considered in relation to pathogenesis