1.1Detection of genomic amplification of the human telomerase gene in normal and dysplastic PAP-smears predicts the development of cervical cancer and reduces false-negative diagnoses in cervical cytologyCGH analyses of human tumors have revealed that chromosomal aberrations result in genomic imbalances specific for different tumor from diverse tissue types. Furthermore, these changes define discrete steps in the progression of epithelial tumors. More than 90% of cervical carcinomas carry extra copies of chromosome 3, which results in the genomic amplification of the human telomerase gene TERC. It is therefore logical to apply the visualization of these recurring and specific chromosomal aberrations to complement and enhance the cytomorphological diagnosis of human cancers and their precursor lesions. This can be achieved using interphase cytogenetics with fluorescently tagged DNA probes that recognize specific chromosomal target regions directly in interphase cells. We could show that the visualization of chromosomal aneupoloidies in cytological preparations (such as cervical Pap-smears or fine needle aspirates from breast lesions) is highly specific and sensitive tests for the diagnosis of cancer and premalignant precursor lesions. For instance, the detection of genomic copy number alterations of the human telomerase gene TERC (which maps to chromosome 3q26) serves as an independent genetic marker for the diagnosis of cervical dysplasia. In addition, the detection of genomic amplification of this gene in Pap smears predicts the development of cervical cancer, and progression of early lesions to higher-grade dysplasia in the absence of amplification of TERC was never observed. This genetic test can therefore become an important addition for the identification of individual risk profiles of progression.1.2Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas (? T3) to preoperative chemoradiotherapyThere is a wide spectrum of tumor responsiveness of rectal adenocarcinomas to preoperative chemoradiotherapy ranging from complete response to complete resistance. We were therefore interested to investigate whether parallel gene expression profiling of the primary tumor can contribute to stratification of patients into groups of responders or non-responders. We have collected pre-therapeutic biopsies from 30 locally advanced rectal carcinomas (determined by rectal ultrasound as uT3 and uT4) and analyzed these samples for gene expression signatures using microarrays. All patients were participants of a phase III clinical trial (CAO/ARO/AIO-94, German Rectal Cancer Trial) and were randomized to receive a preoperative combined modality therapy including 5-fluorouracil and radiation. In an initial set of 23 patients responders and non-responders (measured by T-level down-sizing) showed significantly different expression levels for 54 genes (p less than 0.001). The ability to predict response to therapy using gene expression profiles was rigorously evaluated using leave-one-out cross-validation (LOOCV). Tumor behavior was correctly predicted in 83% of patients (p=0.02). Sensitivity (correct prediction of response) was 78% and specificity (correct prediction of non-response) was 86% with a positive predictive value of 78% and negative predictive value of 86%. These results suggest that pre-therapeutic gene expression profiling may assist in response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. The implementation of gene expression profiles for treatment stratification and clinical management of cancer patients requires validation in large, independent studies, which are now under way.1.3Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumorsLate diagnosis of colorectal carcinomas results in a significant reduction of average survival times.