Sampling several different tumor locations and several tumor-involved lymph nodes may be necessary in order to best predict the course of breast cancer, scientists have learned.

MicroRNAs (miRNAs), which are certain short strands of RNA, have been linked with the progression and metastasis of breast cancer and may provide prognostic information. However, differences in the amount and types of miRNA within breast tumors can be misleading.

A research team led by Stefanie Avril, MD, of the Technical University of Munich, Germany, collected 132 tumor samples from 16 patients who underwent either lumpectomy or mastectomy for large primary invasive breast cancer. The samples were taken from the peripheral, intermediate, and central tumor zones, as well as from two to five axillary lymph node metastases in nine of the patients. The specimens were then analyzed for the expression of four miRNAs and four control genes.

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Considerable differences were found to exist among all four miRNAs within the primary breast cancers. miRNA expression varied significantly from samples both within primary breast cancers and within lymph node metastases from the same patient. “The intratumoral heterogeneity of miRNA expression in breast cancers can lead to significant sampling bias,” wrote the investigators in The Journal of Molecular Diagnostics.

The researchers evaluated the variation of miRNA expression between different patients to demonstrate why the intratumoral heterogeneity may produce misleading results if only a single sample is used. The mean expression of miR31, which is associated with cancer metastasis, from all zones of the primary tumor site in Patient A was significantly lower than the mean expression from all zones of the primary tumor site of Patient B. However, a sample from a single tumor zone from Patient A showed a higher expression level than the lowest case from Patient B.

“This might in part explain conflicting previous findings regarding miRNA expression profiles,” commented Avril in a statement accompanying the release of the study findings.