Sentinel node biopsy and cytokeratin staining for the accurate staging of 478 breast cancer patients

Sentinel lymph node (SLN) mapping is an effective and accurate method of sa mpling the axillary nodal basin for metastatic disease. The SLN is the firs t node to receive afferent lymphatic drainage from the primary tumor. Lymph atic mapping and SLN biopsy have allowed pathologists to perform a more det ailed examination of the SLN(s) and, therefore, provide more accurate stagi ng of the regional lymphatic basin. Recently, more sensitive assays have be en developed to increase the detection rate of micrometastatic to the axill ary lymph nodes. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN detects micrometastatic disease, which is frequently missed on routine hematoxylin and eosin (H&E) histology. Therefore, lymphatic mapping combin ed with CK IHC staining of the SLN provides more accurate staging of the re gional lymph nodes in patients with breast cancer. At Moffitt Cancer Center , 478 patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labe led sulfur colloid. The excised SLNs were examined grossly, by intraoperati ve imprint cytology, by standard H&E histology, and by IHC stains for CK. S LNs that were only CK positive were confirmed malignant by sectioning the b lock, staining with H&E and finding cells with malignant cytology. Lymphati c mapping and CK IHC staining of the SLNs was successfully performed in 478 newly diagnosed breast cancer patients. Twenty-eight patients had unsucces sful lymphatic mapping for an overall failure rate of 5.5 per cent. a total of 134 (28%) patients had positive nodes (N-1) detected. Ninety-three of t hese patients had both H&E and CK-positive lymph nodes, and an additional 4 1 patients had only CK-positive SLN(s). A total of 385 patients had H&E-neg ative SLNs, but only 344 patients had negative SLN(s) defined as both H&E a nd CK negative. Therefore, 41 (10.6%) of the 385 H&E-negative patients were upstaged, because of the detection of malignant cells by cytokeratin IHC s taining of the SLN. Microstaging of SLNs with CK has shifted 10.6 per cent of our patient population from stage I to stage II disease. Undetected micr ometastatic disease to the regional lymph nodes may account for the signifi cant proportion of stage I breast cancer treatment failures. Furthermore, t he ability to accurately stage the axilla by using lymphatic mapping techni ques, SLN biopsy, and more sensitive assays may help identify a subgroup of truly node-negative patients with invasive breast cancer who can avoid the morbidity associated with a complete axillary dissection or systemic chemo therapy. Finally, those patients found to have micrometastatic disease to t he regional lymph nodes can be treated appropriately in a more selective fa shion.