ABSTRACT
Diabetes and prediabetes have become an epidemic in the United States. The keys to battling this public health challenge are effective screening and evidence-based interventions. Studies show that intensive lifestyle interventions, medications, and weight loss surgery can reduce or delay new-onset type 2 diabetes. This article reviews the steps clinicians can take to help patients stay ahead of this disease.
Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Life Style , Prediabetic State/diagnosis , Prediabetic State/therapy , Bariatric Surgery , Diet, Healthy , Exercise , Humans , Weight LossABSTRACT
The purpose of this study was to determine the distribution of and potential significance of laminin 332 (LM332) in breast cancer. Specimens from a population-based cohort (Nâ¯=â¯297) from 1994 to 1995 were stained for estrogen receptor (ER), progesterone receptor (PgR), HER2 and the LM332 ß3 chain. Seventy-five tumors were LM332-positive and 222 were negative. LM332 ß3 stained 16.0% of ER and/or PgR-positive tumors and 73.2% of triple-negative breast cancers (TNBC). Immunoblotting revealed LM332 in TNBC and HER2-positive samples, but not in an ER-positive breast carcinoma or a phyllodes tumor. After 20 years, 172 patients were alive, 43 had died of breast cancer and 82 of other causes. Patients with LM332-positive tumors had significantly worse 5 (Pâ¯<â¯.0001) and 10-year (Pâ¯<â¯.05) overall and breast cancer specific survival. Among patients with LM332 ß3-expressing and ER/PgR-negative carcinomas, 10-year survival was significantly reduced (Pâ¯<â¯.0450). In a multivariate analysis LM332-positive patients had significant hazard ratios of 3.9 with 95% confidence intervals (CI) of 2.0-7.7 and 2.2 with 95% CI of 1.3-3.8 for 5 and 10-year overall survival, respectively. Because tumor cell motility is required for metastasis, the effect of LM332 on MDA-MB-231 migration was determined using siRNA. Knockdown of LM332-specific ß3 and γ2 chains reduced motility without affecting viability. Our observation that LM332 in breast carcinoma is associated with decreased survival provides evidence that LM332 may have a role in the aggressive phenotype of some breast cancers.
Subject(s)
Breast Neoplasms, Male/metabolism , Carcinoma/metabolism , Cell Adhesion Molecules/metabolism , Cell Movement , Triple Negative Breast Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms, Male/genetics , Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , Carcinoma/genetics , Carcinoma/mortality , Carcinoma/pathology , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Invasiveness , Phenotype , Prognosis , Signal Transduction , Time Factors , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology , KalininABSTRACT
Human epidermal growth factor receptor 2 (HER2) status is useful for predicting response to trastuzumab. Fluorescence in situ hybridization (FISH) for HER2 gene amplification is accurate but limited because of cost, the need for fluorescence microscopy, the limited assessment of histology, and the fading of its signal over time. Dual-color in situ hybridization (Dual ISH) is fully automated, is viewable by bright-field microscopy, has a stable signal, and has separate colors for HER2 and chromosome 17 signals. HER2 immunohistochemistry (IHC), FISH, and Dual ISH were performed on 101 breast cancer cases. Sixteen of 17 cases with 3+ HER2 by IHC showed gene amplification by FISH, and 15 showed amplification by Dual ISH. Three of the 2+ IHC cases were either amplified or equivocal by Dual ISH. None of the IHC-negative cases were amplified by either FISH or Dual ISH. Dual ISH agreed with FISH in 93% of cases. Among the 6 discrepancies, 4 were for an equivocal result for 1 test compared with either a positive or a negative result for the other test. The average differences in readings between Dual ISH and FISH in the discrepant cases were only 0.02, with a range of -1.37 to 1.85. Turnaround time for FISH as a send-out test from test ordering to reporting averaged 8.27 workdays, whereas the turnaround time for Dual ISH performed in-house averaged 4.94 workdays (P < .0000001). Our results indicated that automated Dual ISH is a useful method for evaluating HER2 status in a clinical setting.
