Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases.

BACKGROUND: Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ~40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM. METHODS: Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure. RESULTS: EGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54; P<0.01) with a cross-validated HRR of 1.47 (P=0.03). PTGS2 expression was also associated with poor prognosis (HRR 1.60; P<0.01) with a cross-validated HRR of 1.63 (P<0.01). Expression of EGFR and PTGS2 remained prognostic after multivariate analysis with standard clinicopathological variables (cross-validated HRR 1.51; P=0.02 and cross-validated HRR 1.59; P=0.01, respectively). Stratification for the commonly applied systemic therapy regimens demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated with systemic therapy (HRR 1.78; P<0.01 and HRR 1.64; P=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08; P<0.01). Expression of PTGS2 in CRCLM was correlated to expression in patient-matched primary tumours (P=0.02, 69.2% concordance). CONCLUSIONS: EGFR and PTGS2 expressions are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with resectable CRCLM.

Breeding for societally important traits in pigs.

Pig breeding programs traditionally focus on the genetic improvement of production and reproduction traits that have a clear economic value. Because citizens and consumers increasingly attach value to traits that have little or no direct relationship to production costs or to the price of a product, pig breeding organizations want to pay more attention to societally important traits, such as the welfare and health of pigs, the ecological effects of pork production, and the healthiness and sensory quality of pork. Most societally important traits have an economic and a noneconomic value and are sufficiently heritable for effective genetic selection, although many genetic and phenotypic (co)-variances still have to be estimated. However, it often is not clear to a pig breeding organization how it may deal with the noneconomic value of breeding-goal traits. In this study, a retrospective selection-index method is proposed to obtain the proper weights for societally important traits in the breeding goal. First, the genetic-progress space for each breeding-goal trait is explored by increasing the weights, in a stepwise manner, to each societally important trait in the breeding goal, starting from zero. Subsequently, a pig breeding organization can adopt the resulting genetic-progress scenario that it considers most sustainable or most acceptable. The weights underlying the adopted scenario are considered to be the proper breeding-goal weights. The noneconomic value of each societally important breeding-goal trait is found by deducting its economic value from its obtained weight and is thereby expressed in monetary units. In addition to obtaining weights for societally important breeding-goal traits, the proposed method offers the possibility to estimate the societal costs of selecting for economic traits only, as well as the societal benefits and the economic costs of selecting for traits with a noneconomic value. The method is therefore a useful tool for the development of sustainable breeding goals. An example has been worked out for a sow-line breeding program.

Docetaxel alternating with epirubicin and cyclophosphamide: a feasibility study in breast cancer patients.

Docetaxel is one of the most active drugs used in the treatment of breast cancer. However, its major side-effect, myelosuppression, hampers full-dose combination chemotherapy. We have, therefore, developed an alternating schedule of docetaxel with epirubicin and cyclophosphamide, together with granulocyte colony-stimulating factor, to ameliorate neutropenia. We studied the feasibility of such a strategy, decreasing the treatment interval from 21 days to 14 days, thus further increasing the dose intensity. As expected, myelosuppression was common, complicated by neutropenic fever, which did not exceed preset criteria. Other side-effects were also as expected: alopecia, malaise, nausea and vomiting. After two alternating courses of chemotherapy, a partial response was documented in 15 of 17 patients. We conclude that this alternating schedule is very active against breast cancer and warrants further phase II studies.