Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node

Sentinel lymph node (SLN) mapping is an effective and accurate method of axillary nodal evaluation for metastatic disease. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN has found micrometastatic disease previously undetected by routine hematoxylin and eosin (H&E) stains. The purpose of this study is to determine the number of patients who were upstaged or microstaged, i.e., detected to have micrometastatic disease only by combined lymphatic mapping with CK IHC. Two hundred and ten patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised sentinel lymph nodes were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed to be malignant by histologic examination. CK IHC staining was performed on 381 SLNs in 210 breast cancer patients. Forty-seven of 210 patients (22.4%) had positive nodes. Thirty of these 47 patients (63.8%) had both H&E- and CK-positive SLNs, and an additional 17 of the 47 positive patients (36.2%) had only CK-positive SLNs. Seventeen of the 180 patients (9.4%) who were negative on H&E staining were upstaged by CK IHC staining of malignant cells in the SLN. Comparison of tumor size with the total number of node-positive patients demonstrated that 16 of 30 node-positive T0 and T1 patients (53.5%) and 22 of 39 nodes (56.4%) were upstaged by CK IHC staining. T2 and T3 patients were less frequently upstaged by cytokeratin analysis of lymph nodes. Only one of 17 node-positive patients (5.9%) and seven of 34 nodes (20.6%) in patients with T2 and T3 tumors were upstaged. CK IHC staining of SLNs shifted 9.4% of patients from stage I to stage II. There was a significant upstaging influence noted in patients with tumor sizes under 2 cm. This microstaging shift or upstaging may account for the significant proportion of stage I breast cancer treatment failures. Microstaging of the SLNs using more sensitive assays may help identify a subgroup of patients with invasive breast cancer who would benefit from systemic adjuvant treatment, while sparing a disease-free subset of patients the additional risks of toxic adjuvant chemotherapy.