[Improvement of medication safety by identification of genetically predisposed subjects. Personalized clinical strategies and regulatory advices]. / Erhöhung der Arzneimitteltherapiesicherheit durch Identifizierung genetisch prädisponierter Personen. Personalisierte klinische Ansätze und regulatorische Maßnahmen.

BACKGROUND: Because adverse drug events (ADEs) have a high socio-economic impact there is an urgent need for effective prevention. In addition to process-related avoidable errors personalised approaches for the prevention of ADEs should also focus on genetic polymorphisms as potential causative agents. AIM: Using five case reports as examples therapeutic modalities are described to illustrate the clinical impact of prospective testing aimed at estimating the individual risk of susceptible subjects. MATERIAL AND METHODS: The role of the HLA system, the cytochrome P450 family, other metabolic enzymes and transport proteins are described to illustrate the broad range of genetic susceptibility. It is shown, why, when and for whom pretherapeutic tests on genetic polymorphisms are recommended to reduce the risk of ADEs. RESULTS: The determination of genetic susceptibility is already implemented in clinical practice prior to (1) carbamazepine therapy in south-east Asians and (2) treatment with abacavir independent of ethnicity. Before prescribing carbamazepine or abacavir, it is recommended that therapeutic decisions be based on these test results. CONCLUSION: The broad application of personalised medicine used as an effective tool for minimizing ADE risks is limited by the evidence-based benefit for the patient on the one hand and the costs of the test on the other hand.

Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast.

AIMS: This study was performed to determine the diagnostic value of keratin 5/6 (CK 5/6) immunophenotyping on routinely processed breast tissues. METHODS AND RESULTS: Six hundred and ninety-nine breast lesions, including normal tissues as well as benign and malignant lesions in 321 formalin-fixed, paraffin-embedded samples from 158 different patients were investigated immunohistochemically, following wet autoclave pre-treatment for antigen retrieval. In normal breast tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in varying amounts. While myoepithelial immunoreactivity was most pronounced in the duct system, luminal epithelial immunoreactivity was strongest in the terminal duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an expression, whereas in ductal in-situ carcinomas (DCIS) and in infiltrating ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive immunostaining for CK 5/6. CONCLUSIONS: Immunophenotyping of keratin 5/6 expression can be helpful in the diagnosis of atypical hyperplasias and in-situ carcinomas of the breast. It is particularly valuable in the differential diagnosis between benign and atypical proliferative lesions.