The status of the axillary lymph nodes is one of the most important assessments in breast cancer. But, complete or extensive axillary lymph node dissection (ALND) is not without consequences. Especially because of the complication of lymphedema of the arm of the dissected axilla, the intensity of dissection (such as skeletalization of major veins and artery) began to be reduced unless there was reason to believe that widespread node positivity was likely. So, efforts have been made to use the immune cell status pattern in the negative lymph node cases as a surrogate for the risk status of the axillary nodes. 

But, keep in mind that more intense pathology processing of the axillary nodes has cast doubt on the accuracy of past data on node negativity (because the rate of SLN positivity has turned out to be much higher...20% false neg. rate¹...than anticipated from old-style pathology node processing).

Dr. Lee's Study:

Unlike IHC tumor markers, immune-cell population  response profile is a dynamic process related to the timing, the quality and the quantity of antigen stimulation of the nodes.  Basically, the Stanford group found that both CD4 and CD1a cells decrease in tumor-involved SLN & ALN.  CD1a increases in tumor free ALN.  Patients with unfavorable DFS have decreased CD4 and CD1a (like SLN and tumor involved ALN) comparing to CD4 and CD1a status of those patients with favorable DFS.  These findings are based on only 77 patients with diverse tumor grade, size and tumor marker status.  I do not think their findings are convincing at all.  My hunch is that those unfavorable DFS patients "negative" ALN may have tumor antigen that were not detected by their 4 sections of the nodes. That is why those nodes behave like SLN and tumor involved ALN.  If you grind the nodes up and do PCR on them, you probably will be able to detect it. For the website regarding this issue, their abstract is probably good enough.

Dr. Lee's report Abstract:

"We performed immunohistochemical analysis of 47 sentinel and 104 axillary (nonsentinel) nodes from 77 breast cancer patients with 5 y of follow-up to determine if alterations in CD4, CD8, and CD1a cell populations predict nodal metastasis or disease-free survival. Sentinel and axillary node CD4 and CD8 T cells were decreased in breast cancer patients compared to control nodes. CD1a dendritic cells were also diminished in sentinel and tumor-involved axillary nodes, but increased in tumor-free axillary nodes. Axillary node, but not sentinel node, CD4 T cell and dendritic cell populations were highly correlated with disease-free survival, independent of axillary metastasis. Immune profiling of ALN from a test set of 48 patients, applying CD4 T cell and CD1a dendritic cell population thresholds of CD4 ≥ 7.0% and CD1a ≥ 0.6%, determined from analysis of a learning set of 29 patients, provided significant risk stratification into favorable and unfavorable prognostic groups superior to clinicopathologic characteristics including tumor size, extent or size of nodal metastasis (CD4, p < 0.001 and CD1a, p < 0.001). Moreover, axillary node CD4 T cell and CD1a dendritic cell populations allowed more significant stratification of disease-free survival of patients with T1 (primary tumor size 2 cm or less) and T2 (5 cm or larger) tumors than all other patient characteristics. Finally, sentinel node immune profiles correlated primarily with the presence of infiltrating tumor cells, while axillary node immune profiles appeared largely independent of nodal metastases, raising the possibility that, within axillary lymph nodes, immune profile changes and nodal metastases represent independent processes."

References:

1. Yared MA, et. al., "Recommendations for Sentinel Lymph Node Staging in Breast Cancer", Am. J. Surg. Path. 26(3):377-382, 2002.
2. Peter Lee, M. D. @ Stanford U., on-line report.

(posted 10 November 2005)