Spotlight

Abstract

Shabo et al., pp. 780–786 Macrophages and monocytes are known to be important for tumor cell migration, invasion and metastasis, even to the extent that metastatic cells thought to be fusions of tumor cells and macrophages have been reported. In this study the authors investigated whether the monocyte/macrophage lineage markers, CD163, MAC387 and CD68 are expressed in breast cancer tissue of 127 patients. Using tissue microarray, breast cancer tissue from patients followed up for 13 years was tested for these markers. Forty-eight percent of cancer tissue expressed CD163 and 12% expressed MAC387 but CD68 was not expressed. CD163 expression was considered positive if over 25% of the cancer cells expressed it. When breast tissue samples were categorized according to the Nottingham Histologic Grade (NHG) or if they were DNA diploid cancers, patients that were CD163 positive had an increased risk for aggressive breast cancer of 3 or 5.3, respectively. Finally, multivariate analysis showed that CD163 positivity has a prognostic significance in determining both distant recurrence and breast cancer mortality (p = 0.053 and 0.044, respectively). This study shows for the first time that that the monocyte/macrophage CD163 marker is associated with a significantly more aggressive breast cancer disease. CD163 could be a useful prognostic marker for breast cancer and may shed light on the involvement of the monocyte/macrophage lineage in the development of the disease. 3 Distant recurrence-free survival of Nottingham Histologic Grade 1–2 patients and patients with diploid breast cancer as categorized by CD163 positivity. Yanaoka et al., pp. 917–926 Helicobacter pylori (H. pylori) is considered a major risk factor in gastric cancer by causing gastritis that can lead to atrophy and eventually cancer. In this study Yanaoka et al. investigated whether the serum antibody levels of H. pylori and serum levels of pepsinogen (PG) –&!hyphen; also an indicator of gastric tissue integrity — can identify cancer susceptibility in a cohort of asymptomatic middle-aged Japanese men. Analysis of over 5,000 subjects in a 10-year study showed that 63 subjects developed gastric cancers and over 87% of these were H. pylori positive. A 3.5-fold increased risk of gastric cancer was seen in the H. pylori-positive group but this increased risk accelerated to 9.5 after 7 years in a step-wise fashion in patients classified with high antibody levels. When serum levels of PGI or a PGI/II ratio were reduced, the risk of cancer development increased by 4.5. Combining the two indicators, distinct trends were seen. Patients with high H. pylori antibody levels and low PG I or PG/II levels demonstrated an increased incidence rate of about 400/100,000 person-years. Those with a high PGI or PGI/II and a negative H. pylori profile did not develop cancer. The authors also identified a small subgroup of H. pylori-negative patients with low PGI or PGI/II ratio who actually had an increased risk: over 400/100,000 person-years incidence rate. These results show that H. pylori and PG could be very useful as serum markers to reflect future risk of stomach cancer. Lafkas et al., pp. 967–971 p53 mutations in stromal fibroblasts occur in primary breast and other cancers. Previously the authors had shown that p53 mutations in these cells promoted breast cancer growth. In this report, Lafkas et al. investigate whether stromal fibroblasts with and without p53 mutations can have any effect on the outcome of chemotherapy. MCF7 breast cancer cells or PC3 prostate cancer cells were co-injected with p53-positive or -negative fibroblasts into SCID mice. Mice with p53-negative fibroblasts developed tumors more quickly. As soon as the tumors became palpable, mice were treated with the widely used chemotherapeutic agents doxorubicin (DOX) or cis-platinum. Animals with p53-negative fibroblasts were more sensitive, resulting in decreased tumor growth, when treated with DOX and cis-platinum and this effect appeared to be mediated by soluble factors. The authors then asked if this phenomenon was linked to cellular senescence and found that senescence was greatly inhibited in p53-negative fibroblasts treated with DOX or cis-platinum compared to their p53-positive counterparts. Inhibition of senescence is likely to inhibit the paracrine production of growth factors leading to tumor growth. This study shows that stromal fibroblasts can have a substantial effect on anti-cancer therapy and that the presence of tumor suppressor gene p53 in these cells can interfere with the efficacy of DOX or cis-platinum chemotherapeutic agents.