How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists.

Unlabelled: Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas.

Methods: Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing.

Validation of a postfixation tissue storage and transport medium to preserve histopathology and molecular pathology analyses (total and phosphoactivated proteins, and FISH).

Tumor biomarker studies are integral to oncology clinical trials but may yield artifactual results owing to variation in sample procurement and processing. Ethanol, 70% vol/vol, was validated as a sample transport medium using markers of the PI3K/Akt/mTOR pathway. BT474 tumor xenografts were excised and slices were immediately placed into formaldehyde and fixed for 24 hours.

HER2 gene status in primary breast cancers and matched distant metastases.

Introduction: The status of the gene encoding human EGF-like receptor 2 (HER2) is an important prognostic and predictive marker in breast cancer. Only breast cancers with HER2 amplification respond to the targeted therapy with trastuzumab. It is controversial to what degree the primary tumour is representative of distant metastases in terms of HER2 status.

Expression and localization of melanocortin-1 receptor in human adipose tissues of severely obese patients.

Objective: The melanocortin system is a key regulator in the hypothalamus of energy intake and expenditure. It is frequently linked with obesity and apparently modulates sympathetic outflow to white adipose tissues. The role of the melanocortins within adipose tissues, however, is not entirely clear.

Generation and analysis of melanoma SAGE libraries: SAGE advice on the melanoma transcriptome.

In this study, we generated three SAGE libraries from melanoma tissues. Using bioinformatics tools usually applied to microarray data, we identified several genes, including novel transcripts, which are preferentially expressed in melanoma. SAGE results converged with previous microarray analysis on the importance of intracellular calcium and G-protein signaling, and the Wnt/Frizzled family.

Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays.

By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT) and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, and confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT.

HER-2 and TOP2A coamplification in urinary bladder cancer.

HER-2/NEU is one of the most frequently amplified oncogenes and a potential therapeutic target in bladder cancer. In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER-2. To study the amplification and expression of TOP2A and HER-2 and associations with tumor phenotype and clinical outcome in bladder cancer, a tissue microarray containing 2,317 bladder tumor samples was analyzed by FISH and immunohistochemistry.

High frequency of BRAF mutations in nevi.

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer.

The chromosomal region 12q13-q15 is recurrently amplified in bladder cancer. Putative target genes located in this region include MDM2, CDK4, and GLI. To evaluate the involvement of these genes in bladder cancer, we screened a tissue microarray (TMA) containing 2317 samples by fluorescence in situ hybridization (FISH).

Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays.

To explore molecular mechanisms of prostate cancer progression, we applied tissue microarrays (TMAs) to analyze expression of candidate gene targets discovered by cDNA microarray analysis of the CWR22 xenograft model system. A TMA with 544 clinical specimens from different stages of disease progression was probed by mRNA in situ hybridization and protein immunohistochemistry. There was an excellent correlation (r = 0.