• Anne Forde

Chemokine Receptor Link to Colorectal Cancer

Günther et al., pp. 726–733

Colorectal cancer is frequently treated by surgical removal of both the tumor and affected lymph nodes. The procedure, however, is associated with a significant rate of morbidity and mortality. For patients who do not have lymphatic metastasis, a less invasive, that is local treatment would be preferable. Unfortunately, no reliable clinical means of excluding lymph node involvement is currently available.

Members of the homeostatic chemokine family—including the receptors CXCR4, CXCR5, and CCR7—have been shown to play an important role in lymphocyte homing to the secondary lymphoid organs. More recently, chemokine receptor expression has been shown be an important criterion for lymph node metastasis in carcinomas such as breast and stomach.

For this reason, Günther et al. conducted a retrospective study on 99 colorectal cancer patients who had undergone curative surgical resection for tumor expression of CXCR4, CXCR5, and CCR7. In approximately 60% of these patients lymph node metastasis was found.

Both CXCR4 and CCR7 expression were strongly correlated with the presence and degree of lymph node metastasis. CCR7 expression at the invasion front (IF)—an area of the tumor which is considered to be most aggressive—showed a particularly striking correlation with lymph node involvement. Survival analysis showed that patients with CCR7 IF expression had decreased 5-year survival compared with those that lacked its expression (71% versus 96%, p= 0.03).

These data warrant a larger study. CCR7 expression could be a promising diagnostic tool to differentiate between colorectal cancer patients with and without lymphatic metastasis, and thus to avoid lymph node dissection in the latter group. Furthermore, unlike other prognostic indicators (tumor invasion, tumor grading)—as a receptor—CCR7 could theoretically represent a target for a future therapeutic strategy to prevent lymphatic metastasis.

Oxygen-Sensitive Transcription Factor and Breast Cancer Outcome

Dales et al., pp. 734–739

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that plays an important role in cellular oxygen homeostasis. Overexpression of HIF-1α, HIF-1α's oxygen sensitive subunit, is implicated in several human carcinomas, including breast cancer.

Dales and colleagues, therefore, wanted to conduct a large scale (n=745) retrospective study on patients with invasive breast cancer disease to determine what prognostic significance HIF-1α expression levels had on patient outcome.

Using frozen sections of tumor tissue, the authors screened for HIF-1α expression by immunohistochemistry. A cut-off level of 10% HIF-1α expression was determined to be a high and statistically reliable prognostic indicator.

Patients exhibiting high HIF-1α expression had a lower likelihood of overall survival (p=0.019) and were at higher risk of earlier and more widespread metastasis (p=0.008) and disease relapse (p=0.015).

Overall, this study suggests that high HIF-1α expression is associated with poorer prognosis in patients with invasive disease. These results also highlight the potential role of HIF-1α in assisting cancer cell survival in a hypoxic environment, thus perhaps giving them a growth advantage.

Illustration 1.

Kaplan-Meier curve: Breast cancer patients with high HIF-1α expression (≥10%) have a higher risk of developing metastasis (p= 0.008).

Cancer Atlas of India

Nandakumar et al., pp. 740–754

Documentation of cancer incidence in a country as vast as India is not a trivial undertaking. To date, the Indian National Cancer Registry Programme (NCRP) comprises only 6 population-based cancer registries (PBCR).

In an effort to collate cancer incidence from a broader sample, Nandakumar et al. collected data directly from 501 pathology laboratories serving the country's 593 districts. Data on 217,174 microscopically diagnosed cancers over the period 2001–2002 were submitted largely via the internet.

In order to determine how complete the data from various districts were, cancer incidence from the districts was compared to the incidence recorded by a past PBCR study. In all, 82 districts exceeded the PBCR incidence levels and thus were deemed to be representative.

The data generated confirmed some previous results but also gave new insights into national cancer incidence. These include a high rate of the following cancers: mouth cancer in southern states, nasopharynx cancer in the northeast, and stomach cancer in the Mizoram state.

The authors concede that districts with low incidence rates may simply reflect insufficient data collection and, thus, their cancer incidence is not interpretable. Additionally, it is acknowledged that about 15% of cancers are not diagnosed by pathology. However, collecting data directly from pathology laboratories compliments population-based data. It is also an efficient and cost-effective means of generating a cancer atlas that can offer new clues to cancer etiology.