HER2 assessment on core biopsy specimens using monoclonal antibody CB11 accurately determines HER2 status in breast carcinoma.

AIMS: HER2 status is a prognostic factor in breast carcinoma and predicts response to trastuzumab therapy. Trastuzumab is effective in the neoadjuvant, adjuvant and advanced disease settings. Knowledge of HER2 status early in the diagnostic and therapeutic process is vital for treatment planning. HER2 analysis is usually carried out by immunohistochemistry or fluorescence in situ hybridization (FISH). The aim of this study was to establish whether HER2 immunohistochemistry using monoclonal antibody CB11 and carried out on the initial diagnostic core biopsy specimen accurately predicts HER2 amplification status. METHODS AND RESULTS: This is the largest study to date in which HER2 protein expression has been assessed by CB11 immunohistochemistry on the diagnostic core biopsy specimen and correlated with the result of FISH. Using FISH as the definitive HER2 status, we studied 568 invasive breast cancers using CB11 immunohistochemistry on core biopsy. This analysis had a sensitivity of 99.4%, specificity of 93.9%, false-positive frequency of 3.9% and false-negative frequency of 1.1%. These data are as good as those obtained from analysing resection specimens alone in UK national reference centres. CONCLUSIONS: CB11 immunohistochemistry accurately predicts HER2 amplification status and can be reliably carried out on core biopsy specimens of breast carcinoma.

Sentinel nodes are identifiable in formalin-fixed specimens after surgeon-performed ex vivo sentinel lymph node mapping in colorectal cancer.

BACKGROUND: In recent years, the technique of sentinel lymph node (SLN) mapping has been applied to colorectal cancer. One aim was to ultrastage patients who were deemed node negative by routine pathologic processing but who went on to develop systemic disease. Such a group may benefit from adjuvant chemotherapy. METHODS: With fully informed consent and ethical approval, 37 patients with primary colorectal cancer and 3 patients with large adenomas were prospectively mapped. Isosulfan blue dye (1 to 2 mL) was injected around tumors within 5 to 10 minutes of resection. After gentle massage to recreate in vivo lymph flow, specimens were placed directly into formalin. During routine pathologic analysis, all nodes were bivalved, and blue-staining nodes were noted. These later underwent multilevel step sectioning with hematoxylin and eosin and cytokeratin staining. RESULTS: SLNs were found in 39 of 40 patients (98% sensitivity), with an average of 4.1 SLNs per patient (range, 1-8). In 14 of 16 (88% specificity) patients with nodal metastases on routine reporting, SLN status was in accordance. Focused examination of SLNs identified occult tumor deposits in 6 (29%) of 21 node-negative patients. No metastatic cells were found in SLNs draining the three adenomas. CONCLUSIONS: The ability to identify SLNs after formalin fixation increases the ease and applicability of SLN mapping in colorectal cancer. Furthermore, the sensitivity and specificity of this simple ex vivo method for establishing regional lymph node status were directly comparable to those in previously published reports.