Molecular alterations in AKT1, AKT2 and AKT3 detected in breast and prostatic cancer by FISH.

Aims: The AKT family is implicated in cancer progression. There are three mammalian AKT isoforms located on chromosomes 14, 19 and 1, respectively. The aim of the study was to investigate genetic alterations of AKT in breast and prostatic cancers using fluorescence in situ hybridization (FISH).

Prognostic significance of numeric aberrations of genes for thymidylate synthase, thymidine phosphorylase and dihydrofolate reductase in colorectal cancer.

Background: Most human cancer cells have structural aberrations of chromosomal regions leading to loss or gain of gene specific alleles. This study aimed to assess the range of gene copies per nucleus of thymidylate synthase (TYMS), thymidine phosphorylase (TP) and dihydrofolate reductase (DHFR) in colorectal cancer, and to evaluate its prognostic significance following adjuvant chemotherapy, since these enzymes are closely related to efficacy of 5-fluorouracil (5FU).

Patients And Methods: Consecutive patients (n = 314), who were completely resected for colorectal cancer stages II-IV and adjuvantly treated with 5-FU were retrospectively evaluated.

HER4 in breast cancer: comparison of antibodies against intra- and extra-cellular domains of HER4.

Introduction: We have previously linked HER4 expression with increased survival in breast cancer. However, other reports have associated HER4 with adverse prognostic significance. One possible explanation for the conflicting reports may be that these results are antibody dependent.

A multi-centre investigation towards reaching a consensus on the immunohistochemical detection of ERbeta in archival formalin-fixed paraffin embedded human breast tissue.

Estrogen receptor (ER) alpha is a well-established independent prognostic factor in breast cancer whose presence determines the clinical implications of adjuvant endocrine therapy. A second receptor, ERb has been described, and a number of studies have examined its expression in breast tissue. However elucidation of the role played by ERb has been hampered by published immunohistochemical studies employing a variety of protocols and scoring systems such that inter-laboratory comparisons are difficult.

AKT activation predicts outcome in breast cancer patients treated with tamoxifen.

Oestrogen receptor (ERalpha) expression is a strong predictor of response to endocrine therapy. The PI3K/AKT/mTOR signal transduction pathway has been implicated in endocrine resistance in vitro. The present study was carried out to test the hypothesis that AKT activation mediates tamoxifen resistance in clinical breast cancer.

Can molecular markers predict when to implement treatment with aromatase inhibitors in invasive breast cancer?

Purpose: Resistance to tamoxifen is linked to overexpression of HER2, and aromatase inhibitors show particular benefit in progesterone receptor (PR)-negative patients. We previously reported reduced survival in patients overexpressing HER1, HER2, and HER3. We now show that both HER1-3 and PR status predicts for early relapse in estrogen receptor (ER)-positive tamoxifen-treated breast cancer patients.

Outcome and human epidermal growth factor receptor (HER) 1-4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling.

Background: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1-4 status for further clarification of the differing roles for the HER family at a biological level.

8th Nottingham International Breast Cancer Conference, Nottingham, UK, 16-19 September 2003.

The four-day biennial 8th Nottingham Breast Cancer Conference held at the East Midlands Conference Centre, University of Nottingham, UK (16-19 September 2003) once again proved to be a successful event. Recent advances in clinical and scientific research were presented to an international audience, covering a broad spectrum of breast cancer issues including prediction, diagnosis and treatment. Delegates were encouraged to participate in workshop sessions, which allowed the comprehensive discussion of existing and promising future advances in breast cancer care.

Gene amplifications associated with the development of hormone-resistant prostate cancer.

Purpose: Hormone resistance remains a significant clinical problem in prostate cancer with few therapeutic options. Research into mechanisms of hormone resistance is essential.

Experimental Design: We analyzed 38 paired (prehormone/posthormone resistance) prostate cancer samples using the Vysis GenoSensor.

Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer.

EGFr/HER1 and c-erbB-2/HER2 expression are associated with poor prognosis in breast cancer. The type I receptor tyrosine kinase (RTK) family to which they belong has four members (HER1-4). In this study, expression of HER1-4 and oestrogen receptor (ER) expression were determined by immunohistochemistry in 220 breast carcinomas.