Introduction The role of the cellular microenvironment in breast tumorigenesis has become an important research area. However, little is known about gene expression in histologically normal tissue adjacent to breast tumor, if this is influenced by the tumor, and how this compares with non-tumor-bearing breast tissue.

O verexpression of the human epidermal growth factor receptor-2 (HER2) gene, a breast cancer marker, is associated with rapid tumour growth, increased risk of recurrence after surgery, poor response to conventional chemotherapy and shortened survival.1 The availability of targeted trastuzumab (Herceptin) therapy for tumours overexpressing HER2 protein (HER2 positive) has brought the need for accurate determination of HER2 status into sharp focus. Trastuzumab therapy improves the survival rate among women with metastatic or localized HER2-positive breast cancer.2-6 However, trastuzumab has deleterious side effects and a high cost (Can$50 000 per year); 5-9thus, it is important to accurately determine HER2 status.There are 2 tests commonly used to determine HER2 status (Box 1): immunohistochemistry (detects overexpression of HER2 protein) and fluorescence in situ hybridization (detects amplification of the HER2 gene). A widely recommended 11 testing algorithm (referred to here as the base strategy)12 is to consider an immunohistochemistry score of 3+ as positive, a score of 0 or 1+ as negative, and a score of 2+ as ambiguous and requiring confirmation with fluorescence in situ hybridization. Trastuzumab therapy is currently approved in Canada for use in women with either an immunohistochemistry score of 3+ or a positive fluorescence in situ hybridization result. Studies that showed fluorescence in situ hybridization to be more sensitive than immunohistochemistry in determining HER2 status 13,14 and a retrospective analysis that showed trastuzumab therapy to be beneficial only in patients who receive a positive result of fluorescence in situ hybridization 15 have raised the issue of whether fluorescence in situ hybridization should be used to determine the HER2 status of all women with breast cancer. 7,16 In some countries (e.g., Belgium), only patients with a positive result of fluorescence in situ hybridization receive trastuzumab therapy. Testing for HER2-positive breast cancer: a systematic review and cost-effectiveness analysis Background: Testing to determine HER2 status has come into focus since the approval of trastuzumab (Herceptin) for the treatment of HER2-positive breast cancer. We compared the cost-effectiveness of various strategies used to test HER2 status, an important first step toward evaluating the overall cost-effectiveness of trastuzumab therapy.

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BACKGROUND Efficient quality control is essential to ensure high sensitivity of Papanicolaou (Pap) smears. For this purpose, rescreening of 10% random negative smears is increasingly felt to be ineffective. Rapid rescreening (RR) of all negative Pap smears is more practical and has received widespread acceptance, especially in Europe, although its sensitivity is difficult to monitor and its retrospective nature may influence the vigilance of the screeners. The method of rapid prescreening (RPS) overcomes these drawbacks because rapid review of Pap smears precedes full screening. METHODS All routine conventional Pap smears (n = 8364) over 2 months underwent RPS by 12 cytotechnologists, followed by full screening. Data were analyzed to determine correlation between the RPS sensitivity of individual cytotechnologists and both their sensitivity in full screening and their years of experience as cytotechnologists. RESULTS There was a striking variability in sensitivity (15.4%–72.7%) among the 12 screeners with an atypical squamous cells of undetermined significance (ASCUS) threshold. There was no correlation between RPS sensitivity of individual cytotechnologists with either their sensitivity in full screening or their years of experience as cytotechnologists. CONCLUSIONS The skills required of a cytotechnologist for achieving a high sensitivity in RPS are apparently different from those of full screening and are independent of the sensitivity of the screeners at full screening or of the years of experience as cytotechnologists. Cancer (Cancer Cytopathol) 2006; © 2006 American Cancer Society.

The X1Σ italicg+ curves of He2 and Be2 have been calculated by extrapolating the BSSE corrected MRCI total energies obtained with large Gaussian basis sets, large reference configuration spaces, and pseudo‐natural molecular orbitals to an infinite basis. The direct calculated He2 nonrelativistic dissociation energies (De) of 11.0031 K is in excellent agreement with the recent theoretical evaluations, whereas the Be2 nonrelativistic De = 822 cm−1 and relativistically corrected De = 818 cm−1 are in good agreement with most known values including the experimental De = 790 ± 30 cm−1. An analysis of the configuration structure of Be2 wave function and calculated vibration spectrum displays unusual type of chemical bond in this molecule and explains a unique form of the Be2 potential curve. Thus, near the equilibrium point the bond can be classified as a conventional covalent bond, whereas at larger distances, it can be classified as van der Waals interaction. The problems of high precision Be2 potential curve calculations are also discussed. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

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Population stratification results from unequal, nonrandom genetic contribution of ancestors and should be reflected in the underlying genealogies. In Quebec, the distribution of Mendelian diseases points to local founder effects suggesting stratification of the contemporary French Canadian gene pool. Here we characterize the population structure through the analysis of the genetic contribution of 7,798 immigrant founders identified in the genealogies of 2,221 subjects partitioned in eight regions. In all but one region, about 90% of gene pools were contributed by early French founders. In the eastern region where this contribution was 76%, we observed higher contributions of Acadians, British and American Loyalists. To detect population stratification from genealogical data, we propose an approach based on principal component analysis (PCA) of immigrant founders' genetic contributions. This analysis was compared with a multidimensional scaling of pairwise kinship coefficients. Both methods showed evidence of a distinct identity of the northeastern and eastern regions and stratification of the regional populations correlated with geographical location along the St‐Lawrence River. In addition, we observed a West‐East decreasing gradient of diversity. Analysis of PC‐correlated founders illustrates the differential impact of early versus latter founders consistent with specific regional genetic patterns. These results highlight the importance of considering the geographic origin of samples in the design of genetic epidemiology studies conducted in Quebec. Moreover, our results demonstrate that the study of deep ascending genealogies can accurately reveal population structure. Am J Phys Anthropol, 2011. © 2010 Wiley‐Liss, Inc.

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