Dr. Susan Love Research Foundation | I had a sentinel node biopsy. There were two types of tests done. The first, the hematoxylin-eosin stain (H&E), was negative; the second, the cytokeratin immunohistochemical (IHC) stain, was positive. Does this mean the cancer has spread to my lymph nodes? How should I be treated?

Sentinel node biopsy is a procedure designed to find the one node that the surgeon believes is most likely to have cancer cells. This node is then divided into sections and examined carefully. The biopsy procedure entails having the surgeon inject a small amount of blue dye and/or radioactivity into the breast at the site of the lesion. The material passes naturally through the nearby lymphatics to the first draining node for that area of the breast. This is the node that is most likely to have drained any cancer cells spreading through the lymphatics from a tumor in that area, and it is the one that is removed to be examined. The sentinel node biopsy can be done with either lumpectomy or mastectomy, and after a core or open biopsy.

After the sentinel node has been removed, it is cut into many slices and put on slides. The slides are then stained to make the cancer cells more visible. There are two kinds of stains that can be used. One is called the hematoxylin-eosin stain (H&E) stain. The other is the immunohistochemical (IHC) stain.

The standard test has always been the H&E stain, and all of our prognostic estimates have been based on seeing cancer cells in a lymph node through this method of staining. However, the cytokeratin IHC stain, which is more sensitive than the H&E stain, has recently begun to be used to identify cancer cells on sentinel node slides. Because the cytokeratin IHC stain is more sensitive than the H&E stain, it sometimes picks up nodes that are negative on the H&E test. At first we thought this was good thing and would allow for a more accurate diagnosis. What we are finding, however, is that there are often a few cells which are dislodged during surgery that make it to the sinus of the lymph nodes (micrometastases). This situation does not appear to be the same as cancer cells that find their own way to the lymph nodes on their own (macrometastases).

While it might seem logical to think that detecting micrometastases is good, it is actually not clear that this is the case. That's because it doesn't appear that the presence of micrometastases actually signifies that the cancer has spread. It's also not clear that the cells seen in micrometastases have the potential to become malignant.

In their article "Breast Cancer Sentinel Node Metastases: Histopathologic Detection and Clinical Significance," published in Cancer Control in September/October 2001, David Ollila, MD, and Karyn Stitzenberg, MD, reviewed the research that has been conducted on sentinel node biopsies and the H&E and cytokeratin IHC stains. They report that the studies to date have not found that detecting micrometastases through cytokeratin IHC affects overall survival. In other words, there doesn't seem to be a difference in overall survival between women who were initially thought to be node-negative and later had micrometastases detected through cytokeratin IHC and those who truly were node-negative. Because of this, Ollila and Stitzenberg believe that serial sectioning with H&E staining should be the standard test performed and that cytokeratin IHC staining should only be done routinely as part of a clinical trial.

There are two trials now underway that will give us more information and help us to determine whether cytokeratin IHC staining should become a routine part of the sentinel node analysis. One of these trials, ACOSOG Z0010, is evaluating the prognostic significance of sentinel node and bone marrow micrometastases, including cases that are negative by H&E staining. A second study, NSABP B-32, is comparing sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer patients. As part of this comparison, the researchers will look at whether the cytokeratin IHC stain identifies a group of patients with a potentially increased risk for recurrence.

At this point, most experts believe that a positive cytokeratin IHC result following a negative H&E stain is not cause for alarm. Because your H&E test was negative, it would appear that you do not need to have additional nodes removed and that you can proceed with treatment as if you were lymph node-negative.

References:

Ollila DW, Stitzenberg KB. Breast Cancer Sentinel Node Metastases: Histopathologic Detection and Clinical Significance. Cancer Control 2001 Sep–Oct;8(5):407–14.

Dowlatshahi, K, Fan M, Snider HC, Habib FA. Lymph Node Micrometastases from Breast Carcinoma: Reviewing the Dilemma. Cancer 1997 Oct 1;80(7):1188–97.

American Joint Committee on Cancer. Comparison Guide: AJCC Cancer Staging Manual, Fifth versus Sixth Edition. Published 2002.