Semi-quantitative RT-PCR assessment of molecular markers in breast large-core needle biopsies
Abstract:
Large-core needle biopsies are frequently used for the preoperative evaluation of the breast lesions. In addition to initial diagnostic information, they can show the status of molecular markers with predictive and prognostic value and further contribute to an optimal selection of treatment strategy. So far, the potential use of large-core needle biopsies in assessment of marker profile of the breast lesions was studied using the immunostaining approaches. In this work, we sought to determine whether analysis of the large-core needle biopsy by semi- quantitative reverse-transcription polymerase chain reaction reveals molecular data that correspond with the marker status of the subsequently removed tumor. Five molecular markers including ER, PR, c-erbB-2/HER-2/neu, c-erbB-3/HER-3, and CD44 were assessed on mRNA isolated from 23 large-core needle biopsies and corresponding surgical breast cancer specimens using ß2- microglobulin as an internal standard. Significant or highly significant correlation between core biopsies and excised tumors was observed for each marker when the mRNA expression status was scored as positive or negative, with the concordance of the data ranging from 73.9% to 86%. Using the dichotomous scoring, majority of the biopsies (75%) displayed molecular profile that was either identical to the profile of the related tumor specimen, or with the difference in one marker. However, no significant correlation was found when the levels of the markers were expressed as continuous variables, possibly due to intratumoral cell heterogeneity. These results suggest potential usefulness and reliability of semi-quantitative RT PCR in the evaluation of large- core needle biopsies with regard to marker positivity or negativity. On the other hand, the marker-related data expressed as continuous variables cannot be accurately assessed on the large- core needle specimens using this approach, indicating the need for methodological improvements.