Typical medullary breast carcinomas have a basal/myoepithelial phenotype

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-fine mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n = 44) and non-TMBC grade III with no or low scores (n = 160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n = 17) and non-MBC grade III cases (n = 140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R = 2.29), MIB1 > 50 (R = 3.80), ERBB2 negativity (R = 2.24) and p53 positivity (RR = 1.45). Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Smoking and schizophrenia: is symptom profile related to smoking and which antipsychotic medication is of benefit in reducing cigarette use?

Smoking rate is disproportionately high among patients with schizophrenia, resulting in significant morbidity and mortality. However, cigarette smoking has been reported to have beneficial effects on negative symptoms, extrapyramidal symptoms, cognitive functioning and mood symptoms. Therefore, smoking cessation may worsen disability in schizophrenia. The association between smoking and these key clinical parameters was examined. Additionally, severity of smoking across four different antipsychotic treatment groups was explored. One hundred and forty-six patients with schizophrenia were assessed for smoking using expired carbon monoxide and smoking history. They were administered the Positive and Negative Symptom Scale, The Extrapyramidal Symptom Rating Scale, the Barnes Akathisia Rating Scale, Reitans Trail-making Test (A and B) and General Health Questionnaire-28. There was no difference in the chlorpromazine equivalent dose of any of the medications studied. Atypical agents were associated with significantly lower levels of smoking when compared with typical medications. There was no difference in smoking severity between the individual atypical medications examined. Similarly, there were no significant differences between smoking and non-smoking groups with regard to Positive and Negative Symptom Scale, Extrapyramidal Symptom Rating Scale, Trail-making Test and General Health Questionnaire-28. However, there was a significant difference between these groups with the smoking group demonstrating less akathisia. Smoking is not associated with positive, negative cognitive and mood symptoms in schizophrenia. Smoking is associated with lower levels of antipsychotic induced akathisia. Clinicians should not be discouraged from helping patients stop smoking for fear of worsening symptoms. However, akathisia may emerge upon cessation of smoking. Switching patients from typical to atypical antipsychotics may assist patients with schizophrenia to give up smoking.