Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor A, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per fiveunit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; P heterogeneity = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; P heterogeneity = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(3):439 -43)

Abstract. Epithelial tissues achieve a highly organized structure due to cell-cell junction complexes. Carcinogenesis is accompanied by changes in cell interactions and tissue morphology, which appear in the early stages of benign tumors and progress along with invasive potential. The aim of the present study was to analyze the changes in expression levels of genes encoding intercellular junction proteins that have been previously identified to be differentially expressed in colorectal tumors compared with normal mucosa samples (fold change, >2.5) in genome-wide expression profiling. The expression of 20 selected genes was assessed using quantitative reverse transcription polymerase chain reaction in 26 colorectal cancer, 42 adenoma and 24 normal mucosa samples. Between these tissue types, differences were observed in the mRNA levels of genes encoding adherens junction proteins (upregulation of CDH3 and CDH11, and downregulation of CDH19 and PTPRF), tight junction proteins (upregulation of CLDN1 and CLDN2, and downregulation of CLDN5, CLDN8, CLDN23, CLDN15, JAM2 and CGN) and desmosomes (upregulation of DSC3 and DSG3, and downregulation of DSC2), in addition to a decrease in the expression of certain other genes involved in intercellular connections: PCDHB14, PCDH7, MUPCDH and NEO1. The differences between tissue types were statistically significant, and separate clustering of normal adenoma and carcinoma samples was observed in a hierarchical clustering analysis. These results indicate that the morphological changes in neoplastic colon tissue that occur during the 'adenoma-carcinoma sequence' are accompanied by specific changes in the expression of multiple genes encoding the majority of cell-cell junction complexes. The particular differential expression patterns appear to be consistent among patients with cancer and adenoma, in addition to normal mucosa samples.

Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-a and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-a, ER-b, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUA TM ). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women ( p-trend 5 0.01, both comparisons), whereas among postmenopausal women, PR levels were associated directly with BMI ( p-trend 5 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) 5 0.86 (95% CI 5 0.69-1.07) for low PR and HER2 expression vs. OR 5 1.78 (95% CI 5 1.25-2.55) for high expression (p-heterogeneity 5 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers. ' 2007 Wiley-Liss, Inc.Key words: breast; etiology; hormones; epidemiology Amassing data suggest that breast cancers are characterized by ''molecular portraits'' that are established at inception, remain stable over time and represent critical determinants of tumor biology.1 Hormone receptor status is a key parameter in molecular classifications of breast cancer, 2,3 which serves as a marker of hormone-dependent growth and predictor of responsiveness to hormonal treatments. Consequently, researchers have hypothesized that etiologic factors mediated by hormones might be more strongly associated with breast cancers that express hormone receptors when compared with those that are receptor-negative. 4,5 A recent literature review found evidence that nulliparity, late age at first birth and postmenopausal obesity are associated with greater risk for estrogen receptor-a (ER-a)-positive cancers when compared with ER-a-negative tumors, and that early menarche was more strongly linked to tumors coexpressing ER-a and progesterone receptor (PR). 4 Subsequently, a metaanalysis updating this review affirmed the heterogeneous associations for nulliparity and late age at first birth, but not for age at menarche. 5 However, results of studies have not been entirely consistent, especially when limited by small sample sizes,...

A veterinarian presented with multiple erythematous tender nodules over his right hand and arm. One month prior to the appearance of the lesions, he had treated a cat imported from Brazil who had ulcerated pustular cutaneous lesions. Despite antibiotic treatment there had been no improvement in his symptoms.Biopsies from the patient were sent for histology, bacterial and fungal culture. Periodic acid-Schiff (PAS) stains showed a PAS positive oval yeast-like micro-organism with surrounding necrosis. Fungal cultures resembling Sporothrix species grew after 18 days with typical appearances seen on direct microscopy; this was confirmed as Sporothrix brasiliensis on 18S PCR. The patient was treated with oral itraconazole.This is a unique case of cutaneous S. brasiliensis acquired from an infected imported cat. S. brasiliensis is a rare pathogen in the UK. This case has clinical relevance due to its unusual aetiology and in raising awareness of rarer infections associated with importation of pets and global travel. Clinicians should be aware of sporotrichosis as a differential diagnosis for cutaneous and extracutaneous infection in patients with a high risk of exposure, as well as the use of appropriate diagnostic tests.

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