Tumor angiogenesis as prognostic and predictive marker for chemotherapy dose-intensification efficacy in high-risk breast cancer patients within the WSG AM-01 trial.

The goal of this analysis was to characterize the survival impact of angiogenesis in the patients with high-risk breast cancer, particularly the predictive impact on benefit from dose intensification of adjuvant chemotherapy. Formalin-fixed tissue sample of 152 patients treated as part of the WSG AM-01 trial by either high-dose or conventional dose-dense chemotherapy were analyzed. Angiogenic activity was measured using microvessel count and vascular surface area (VSA) determined by the expression of vascular markers CD31 (n = 128) and CD105/endoglin (n = 130).

Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy.

In Ewing's sarcoma family of tumours (ESFT), the clinically most adverse prognostic parameters are the presence of tumour metastasis at time of diagnosis and poor response to neoadjuvant chemotherapy. To identify genes differentially regulated between metastatic and localised tumours, we analysed 27 ESFT specimens using Affymetrix microarrays. Functional annotation of differentially regulated genes revealed 29 over-represented pathways including PDGF, TP53, NOTCH, and WNT1-signalling.

Poor outcome in estrogen receptor-positive breast cancers predicted by loss of plexin B1.

Purpose: A common characteristic of mammary carcinomas is an inverse relationship between the estrogen receptor (ER) status and the proliferative activity of the tumor. Yet, a subset of ER-positive breast cancers is characterized by a high proliferation, suggesting malfunctions in ER responsiveness that influence the biological and therapeutic behavior of tumor cells. The expression of several ER-dependent genes seems to be dysregulated among those "uncoupled" tumors.

Protein expression profiling in high-risk breast cancer patients treated with high-dose or conventional dose-dense chemotherapy.

Purpose: To characterize the prognostic and predictive impact of protein expression profiles in high-risk breast cancer patients who had previously been shown to benefit from high-dose chemotherapy (HDCT) in comparison to dose-dense chemotherapy (DDCT).

Experimental Design: The expression of 34 protein markers was evaluated using tissue microarrays containing paraffin-embedded breast cancer samples from 236 patients who were randomized to the West German Study Group AM01 trial.

Results: (a) 24 protein markers of the initial panel of 34 markers were sufficient to identify five profile clusters (subtypes) by K-means clustering: luminal-A (27%), luminal-B (12%), HER-2 (21%), basal-like (13%) cluster, and a so-called "multiple marker negative" (MMN) cluster (27%) characterized by the absence of specifying markers.

Expression analysis of pancreatic cancer cell lines reveals association of enhanced gene transcription and genomic amplifications at the 8q22.1 and 8q24.22 loci.

Despite tremendous effort and progress in the diagnostics of pancreatic cancer with respect to imaging techniques and molecular genetics, only very few patients can be cured by surgery leading to a 5-year survival rate of only 3%. Especially the lack of chemotherapeutical options in this entity requires a better understanding of the molecular mechanisms leading to pancreatic carcinoma growth and progression in order to develop novel treatment regimens. To identify signaling pathways that are critical for this tumor entity, we compared six well-established pancreatic cancer cell lines (Capan-1, Capan-2, HUP-T3, HUP-T4, KCL-MOH, PaTu-8903) with colon cancer cell lines and tumor cell lines of non-epithelial origin by expression profiling.