Spotlight

Abstract

Chan et al., pp. 474–485 For women with breast cancer the odds of survival dramatically change when the tumor progresses from in situ carcinoma to infiltrative cancer. While the noninvasive form causes death in 1% or less, 28–50% of patients with invasive cancer die. The transition from in situ to infiltrative tumor is therefore a key step in breast cancer development. However, current models for studying this step are limited. Chan and colleagues used a rat model, which recapitulated phenotypic changes observed in the in situ- to-invasive transition. They treated rats with N-methyl-N-nitrosourea (NMU), a widely used carcinogen to experimentally induce mammary tumors. Although NMU-induced tumors are typically low-grade in situ carcinomas, they can develop the capacity for invasion following serial transplantation. These scientists found that the majority of transplanted lineages maintained a ductal morphology and biomarker expression, characteristics of noninvasive tumors. In addition, two histological types of invasive tumors were observed: a mesenchymal lineage that resembled human breast carcinosarcomas and one series of transplants that resembled the recently recognized “basal-like” human breast cancer subtype. When the authors compared noninvasive and highly invasive tumors by gene-expression profiling they identified a total of 136 genes that were upregulated in highly invasive tumors. In addition, they identified 83 genes that were downregulated. Both lists included genes involved in cell adhesion, the extracellular matrix, cell cycle progression and signal transduction. The authors propose that a “reprogramming” in gene expression occurs at the in situ-to-invasive transition, leading to a gradual change in the state of cell differentiation. Dimitriadis et al., pp. 486–494 The best established prognostic factor in colorectal cancer is clinical staging. However, within one clinical stage individual survival rates vary, indicating that subgroups of patients exist with predispositions for early recurrence or resistance to current therapeutic strategies. Dimitriadis and colleagues have identified a new molecule that is associated with frequent metastases, early recurrence and short survival in patients with colorectal cancer. This molecule, CRD-BP/IMP1, is a member of the VICKZ family, which is predominantly expressed during embryonal life. It possesses several recognition motifs for ribonucleoproteins and RNA and is implicated in the posttranslational regulation of several genes, including the F-box protein βTrCP1, which is itself linked to colorectal carcinogenesis. When the authors examined expression of CRD-BP/IMP1 in colorectal tumors, they found that, in 50% of the specimens, the factor was markedly expressed, while only a few cells were immunoreactive in normal tissue. Strikingly, the positive cells in normal tissue were located predominantly at or near the bottom of the crypts, a characteristic localization of stem cells, raising the possibility that CRD-BP/IMP1 is a marker for intestinal stem/progenitor cells. Patients with tumors lacking CRD-BP/IMP1 expression had a favorable clinical outcome. By multivariate analysis the absence of CRD-BP/IMP1 expression was found to be an independent, favorable prognostic factor for survival (p = 0.015). In contrast, CRD-BP/IMP1-positive tumors metastasized or recurred more frequently and characterized a subgroup of patients with shorter survival. These data support the model that abnormal expression of CRD-BP/IMP1 may serve as a useful clinical marker to identify subgroups of patients with a poor prognosis, independently of clinical staging. Menvielle et al., pp. 649–655 Alcohol can cause cancer, including malignancies of the upper aerodigestive tract (oral cavity, pharynx, larynx and esophagus) and liver. Mortality from alcohol-related cancers is often linked to socioeconomic status, with higher death rates in individuals with a lower socioeconomic status. Menvielle and colleagues combined data from longitudinal studies performed in 13 European countries to examine the role of alcohol in socioeconomic inequalities in cancer mortality in men. The contribution of alcohol to socioeconomic inequalities in cancer mortality was 29–36% in France and the Spanish populations, 17–23% in Switzerland and Turin (Italy) and 5–15% in Belgium and the Nordic countries. The difference was most prominent in France, showing the highest mortality rate among men with lower secondary education and the lowest mortality rate among men with a higher education. These results suggest that alcohol use substantially influences socioeconomic inequalities in male cancer mortality in France, Spain and Switzerland but not in the Nordic countries or in Belgium.