A large-scale candidate gene approach identifies SNPs in SOD2 and IL13 as predictive markers of response to preoperative chemoradiation in rectal cancer.

Neoadjuvant radiochemotherapy followed by total mesorectal excision is now the standard treatment for locally advanced rectal cancer. However, tumor response to chemoradiation varies widely among individuals and cannot be determined before the final pathologic evaluation. The aim of this study was to identify germline genetic markers that could predict sensitivity or resistance to preoperative radiochemotherapy (RT-CT) in rectal cancer. We evaluated the predictive value of 128 single-nucleotide polymorphisms (SNPs) in 71 patients preoperatively treated by RT-CT. The selected SNPs were distributed over 76 genes that are involved in various cellular processes such as DNA repair, apoptosis, proliferation or immune response. The SNPs superoxide dismutase 2 (SOD2) rs4880 (P=0.005) and interleukin-13 (IL13) rs1800925 (P=0.0008) were significantly associated with tumor response to chemoradiation. These results reinforce the idea of using germline polymorphisms for personalized treatment.

[Technical considerations for KRAS testing in colorectal cancer. The pathologist's point of view]. / Aspect technique de la détermination du statut KRAS dans le cancer colorectal et mise en place en France. Point de vue de l'anatomopathologiste.

The KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-EGFR (epidermal growth factor receptor) antibodies, such as cetuximab (Erbitux) or panitumumab (Vectibix). KRAS mutations are unambiguously linked to a lack of response to these targeted therapies and to a poor outcome. The optimal determination of the KRAS status should be based on coordination between pathologists and biologists. The pathologist must morphologically check the tumor to be analyzed and be sure that the fixatives used are valuable for molecular biology. The pathologist's involvement may also concern the DNA extraction and the KRAS mutations analyses. This involvement has to be included in a multidisciplinary setting in order to get rapid and robust tests for the clinical use. The imperative knowledge of the KRAS status in the management of metastatic disease represents a good example of this multidisciplinary coordination. In the future, the pathologist's role should be extended, considering the emergence of a more and more personalized medicine, integrating efficiency and cost-effectiveness. Thus, the pathologist may contribute to validate new molecular tests and to offer his specific techniques for translational research.

Increased expression of class III beta-tubulin in castration-resistant human prostate cancer.

BACKGROUND: Class III beta-tubulin (betaIII-tubulin) is expressed in tissues of neuronal lineage and also in several human malignancies, including non-small-cell lung carcinoma, breast and ovarian cancer. Overexpression of betaIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, betaIII-tubulin expression remains largely uncharacterised in prostate cancer. METHODS: In this report, we evaluated the expression of betaIII-tubulin in 138 different human prostate tumour specimens by immunohistochemistry from patients with hormone-treated or hormone-untreated prostate cancer. betaIII-tubulin expression was also examined in various prostatic cancer cell lines including in androgen-sensitive human prostate cancer cells, LNCaP, grown in androgen-depleted medium in 2D cultures or as tumour xenografts when the host mouse was castrated. RESULTS: Whereas moderate-to-strong betaIII-tubulin expression was detected in only 3 out of 74 (4%) hormone-naive tumour specimens obtained from patients who never received hormone therapy, 6 out of 24 tumour specimens (25%) from patients treated for 3 months with neoadjuvant hormone therapy and 24 out of 40 (60%) castration-resistant tumour specimens from chronic hormone-treated patients were found to express significant levels of betaIII-tubulin. These findings were supported by in vitro and in vivo settings. CONCLUSION: Our data indicate that betaIII-tubulin expression is augmented in prostate cancer by androgen ablation and that the expression of this beta-tubulin isoform is associated with the progression of prostate cancer to the castration-resistant state, a stage largely responsible for mortality from prostate cancer.