Isolated Tumor Cells and/or Micrometastasis in Breast Sentinel Lymph Nodes Can Be the Result of Innocuous Passive Dissemination
BB Shetuni, S Simpson, K Yearsley, Y Xiao, SH Barsky. The Ohio State University College of Medicine, Columbus, OH
Background: Increased sensitivity of breast cancer cell detection with cytokeratin IHC has resulted in the detection of isolated tumor cells (ITCs) (<0.2 mm) and micrometastasis (MM) (>0.2 mm, <2mm) in a significant percentage of sentinel lymph nodes (SLNs) negative by H&E, yet the clinical significance of these findings remains unknown.
Design: We examined these questions by conducting comparative studies of patients having undergone SLN dissections with patients having undergone de novo full axillary dissections. Both the presence of tumor cells as well as their stem cell composition defined by aldehyde dehydrogenase positivity (ALDH1+) was investigated in 4 groups of 100 patients each: H&E negative SLNs, H&E positive SLNs, H&E negative axillary dissections and H&E positive axillary dissections. The distribution of the primary breast cancers in each group (histology limited to infiltrating ductal carcinomas) were age, size and biomarker matched (p=0.5). We also presumed that a full axillary dissection would, by definition, include the SLNs.
Results: In the H&E SLN negative group, cytokeratin IHC detected ITCs in 12% and MM in 6% of the cases. In the H&E axillary negative group ITCs were present in only 3% and MM in only 1% of cases. The difference in the detection of cytokeratin positive cells (either ITCs or MM) in the SLN v axillary group was highly significant (p=0.01). Both the SNL and axillary H&E positive groups exhibiting >2mm macrometastasis contained a similar percentage of ALDH1+ stem cells (5-15%) whereas the SNL and axillary H&E negative groups containing only cytokeratin positive ITCs or MM exhibited rare (0-2%) ALDH1+ immunoreactivity (p=0.01). In the former groups of SNL and axillary positive macrometastasis, the ALDH1+ percentage was always greater than that exhibited by the primary tumor (p=0.05) whereas in the latter groups of SNL and axillary ITCs or MM, the ALDH1+ percentage was less than that of the primary tumor (p=0.05).
Conclusions: Given the fact that the SLN procedure involves extensive physical manipulation of the breast following radioactive dye injection, manipulations absent in de novo axillary dissections, our finds suggest that ITCs and/or MM in SLNs can be the result of passive dissemination. Since passive dissemination, in contrast to active metastasis, would not select for stem cells responsible for clonogenic potential, the finding of decreased ALDH1+ in ITCs and MM suggest that passive metastasis in the setting of SLNs may be innocuous.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 48, Monday Morning