AIM:To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.
METHODS:Formalin fixed, paraffin embedded pretherapeutical tumor biopsies (n = 22) and posttherapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan realtime PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.
RESULTS:Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a
Pre-operative 5-fluorouracil (5-FU)-based chemoradiotherapy in locally advanced rectal cancer (UICC-II/III) may significantly reduce local tumour mass. Response to pre-operative treatment, however, varies significantly. Thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are thought to be important predictors for the efficiency of 5-FU-based treatment. The aim of this study was to determine the correlation between TS-, TP-, and DPD-gene expression and the response to 5-FU-based long-term pre-operative chemoradiotherapy assessed by histopathological tumour regression. Additionally, the predictive value of intra-tumoural TS-, TP-, and DPD-gene expression in pre-operative rectal tumour biopsies was assessed by correlation with the histopathological regression grade. Formalin-fixed, paraffin wax-embedded pre-operative biopsies (n = 14) and surgical resection specimens (n = 40) from patients with rectal carcinoma (clinical UICC stage II/III) receiving neo-adjuvant 5-FU-based chemoradiotherapy were studied for TS-, TP-, and DPD-gene expression by quantitative TaqMan real-time PCR after laser microdissection. Results were compared with standardized histopathological tumour regression analysis. There was a significant association between low TS-gene expression in pre-operative tumour biopsies and tumour response (p = 0.02). TS- and TP-gene expression was significantly lower in resection specimens of responders than of non-responders (p = 0.02) when microdissection was used. Statistical significance was even higher when TS and TP were combined (p = 0.0001). For the DPD gene, no significance was found at all. In conclusion, this study shows that TS gene expression in a pretreatment biopsy predicts the response of local rectal cancer to neo-adjuvant 5-FU-based chemoradiotherapy in a high percentage. Moreover, intra-tumoural TS- and TP-gene expression in surgical rectal specimens after neo-adjuvant chemoradiotherapy correlates significantly with histopathological tumour regression when microdissection is applied.
This paper reports a fundamentally new concept for internet-based telemicroscopy. By separating a telemicroscopy application into three tasks - microscope control program, external server, and client application - it is possible to establish a telemicroscopy session between two arbitrary end points on the Internet even if both of the end points are secured by firewall (microscope and client application). The advantages of such a distributed system, compared with the classical point-to-point systems, are discussed. The telemicroscopy system is combined with a telepathology database, which is capable of automatically recording telemicroscopy sessions, allowing a convenient combination of interactive remote microscopy and store and forward telepathology. In addition to remote primary diagnosis, it is easily possible to discuss difficult cases within dedicated user groups, no matter whether images originate from a telemicroscopy session, or are manually entered into the database.
Image cytometric DNA measurements provide data which are most often interpreted as equivalent to the chromosomal ploidy although the chromosomal and the DNA ploidy are not identical. The common link between them is the cell cycle. Therefore, if destined for DNA ploidy interpretations, the DNA cytometry should be performed on a population‐oriented stochastic basis. Using stochastic sampling the data can be interpreted by applying the rules of stochastic processes. A set of statistical methods is given that enables a DNA histogram to be interpreted objectively and without human interaction. These statistics analyse the precision and accuracy of the entire measurement process. They give in error probabilities for accepting a measurement as reliable, for recognition of stemlines, stemline aneuploidy, and for evaluating so‐called rare events. Nearly 300 image cytometric DNA measurements from breast cancers and rat liver imprints examples have been selected to demonstrate the efficiency of the statistics in each step of interpreting DNA histograms.
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