Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients

INTRODUCTION: The HER (human EGFR related) family of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology. It constitutes a complex network, coupling various extracellular ligands to intracellular signal transduction pathways resulting in receptor interaction and cross-activation. The most famous family member is HER2, which is a target in Herceptin therapy in metastatic status and also in adjuvant therapy of breast cancer in the event of dysregulation as a result of gene amplification and resulting protein overexpression. The HER2-related HER receptors have been shown to interact directly with HER2 receptors and thereby mutually affect their activity and subsequent malignant growth potential. However, the clinical outcome with regard to total HER receptor state remains largely unknown. METHODS: We investigated HER1-HER4, at both the DNA and the protein level, using fluorescence in situ hybridisation (FISH) probes targeted to all four receptor loci and also immunohistochemistry in tissue microarrays derived from 278 breast cancer patients. RESULTS: We retrospectively found HER3 gene amplification with a univariate negative impact on disease-free survival (hazard ratio 2.35, 95% confidence interval 1.08 to 5.11, p = 0.031), whereas HER4 amplification showed a positive trend in overall and disease-free survival. Protein expression revealed no additional information. CONCLUSION: Overall, the simultaneous quantification of HER3 and HER4 receptor genes by means of FISH might enable the rendering of a more precise stratification of breast cancer patients by providing additional prognostic information. The continuation of explorative and prospective studies on all HER receptors will be required for an evaluation of their potential use for specific therapeutic targeting with respect to individualised therapy

Molecular typing of Mycobacterium kansasii using pulsed-field gel electrophoresis and a newly designed variable-number tandem repeat analysis

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Changes of tear film and tear secretion after phacoemulsification in diabetic patients

Objective: To evaluate tear film stability and tear secretion in patients with diabetes after phacoemulsification. Methods: Twenty-five diabetic cataract patients and 20 age-matched non-diabetic cataract patients as control underwent phacoemulsification. Tear film break-up time (TFBUT), Schirmer I test (SIT), corneal fluorescein staining, and dry eye symptoms were measured pre- and postoperatively. Results: Diabetics had a decreased preoperative TFBUT and SIT. TFBUT was reduced on Day 1 and recovered on Day 180 postoperatively in both groups. SIT was increased after phacoemulsification, but returned to preoperative levels by Day 180 in non-diabetics, whereas it was lower than preoperative level in diabetics. Positive corneal fluorescein staining was elevated in both groups, and returned to preoperative levels only in controls. Dry eye symptoms were similar to fluorescein staining in both groups. Conclusion: Tear secretion was reduced in diabetic cataract patients after phacoemulsification, which worsened dry eye symptoms and predisposed those patients to ocular damage