Tumor expression of podocalyxin predicts breast cancer progression

Tumor expression of the anti-adhesin podocalyxin independently predicts breast cancer progression, according to a report in the August 1st issue of Cancer Research.

“Molecular profiling is starting to yield concrete results that will help physicians provide a more accurate prognosis in those cases where the classical TMN staging and histopathology are not particularly illuminating,” Dr. Calvin D. Roskelley from University of British Columbia, Vancouver, told Reuters Health.Dr. Roskelley and colleagues assessed changes in podocalyxin expression in 272 invasive human breast carcinomas using a tissue microarray linked to long-term outcome data.Podocalyxin expression was absent in most (60%) invasive breast tumor samples, the authors report. Expression was low in 35% and high in 6% of the cases.High podocalyxin expression was associated with significantly lower disease-free and overall survival than low/no podocalyxin expression, the report indicates, and mean survival time was significantly lower in the high podocalyxin group (9.0 years) than in the low/no podocalyxin group (15 years).High podocalyxin expression was independently associated with poor outcome, the researchers note, with a relative risk as great as or greater than those associated with regional lymph node involvement of Her-2/neu overexpression.In in vitro experiments, podocalyxin-transfected MCF-7 breast carcinoma cells showed perturbed cell junctions, the investigators report, suggesting that this anti-adhesive property may contribute to metastatic progression.”Some tumor subgroups may be predetermined to metastasize based on a molecular signature that emerges early in the disease process,” Dr. Roskelley explained. “It is possible that podocalyxin overexpression could be one component of such a molecular signature.””This possibility is supported by the fact that there was no positive correlation between increased podocalyxin and lymph node infiltration,” Dr. Roskelley added. “Thus, it could be concluded that podocalyxin overexpression identifies node-negative (i.e., earlier) tumors that will progress, which is important given that 70% to 80% of grade 2 tumors without nodal involvement will be fine, in terms of long-term outcome, with conservative treatment only.”(Source: Cancer Res 2004;64:5068-5073: Reuters Health News: Will Boggs, MD: Oncolink: August 2004.)