Patterns of metastatic spread in early breast cancer.

AIMS: The aim of this study was to prospectively investigate metastatic pathways of spread to lymph node versus bone marrow and identify biological characteristics that determine these patterns in early invasive breast cancer. PATIENTS AND METHODS: In all, 177 patients with early invasive breast cancer underwent surgical extirpation of the primary tumour with sentinel lymph node biopsy (SLNB). Bone marrow (BM) aspiration was performed to screen for cytokeratin-positive cells by immunocytochemistry. Lymphatic spread was assessed by histopathological examination of lymph nodes (LN). A representative subset of 87 tumours was analysed by tissue microarray (TMA) to evaluate expression of markers that potentially influence haematogenous vs. lymphatic spread. Patients were followed up for a median of 54.7 months. RESULTS: Of the 177 patients, 114 (64%) were BM-/LN-, 38 (22%) BM-/LN+, 19 (11%) BM+/LN- and 6 (3%) BM+/LN+. Multivariate analysis of histopathological characteristics revealed that increasing tumour size was significantly associated with both LN positivity (p = 0.003) and BM positivity (p = 0.01), the presence of lymphovascular invasion significantly correlated with LN+ (p = 0.01), whereas lower histological grade was significantly associated with BM+ (p = 0.03). LN+ and BM+ were non-significantly negatively related to each other. Univariate analysis of the TMA data showed differential expression patterns for several factors; significant differences between effects on the two metastatic pathways (lymphatic vs. haematogenous) were found for expression of CD54 (p = 0.03), osteopontin (p = 0.04), bone sialoprotein (p = 0.04) and CXCR4 (p = 0.009). High expression of CD54, osteopontin and bone sialoprotein (BSP) was positively associated with BM + but was either not associated, or negatively associated, with LN+. High CXCR4 expression was positively associated with LN+ and negatively with BM+. High VEGF-C expression was associated with both LN+ and BM+, although this did not attain statistical significance. Due to the small number of clinical events during clinical follow-up, no associations were identified between metastatic spread patterns, recurrence and/or death. CONCLUSION: These findings suggest that distinct lymphatic and haematogenous metastatic pathways exist in early breast cancer and that these pathways are governed by specific biological markers.

The value of immunohistochemistry in sentinel lymph node histopathology in breast cancer.

The optimal protocol for the histopathological examination of sentinel lymph nodes (SLNs) in breast cancer has not been determined. The value of more detailed examination using immunohistochemistry (IHC) is controversial. A total of 476 SLNs from 216 patients were reviewed. Sentinel lymph nodes were sectioned at three levels at 100 mum intervals and stained with haematoxylin and eosin (H&E). If the H&E sections showed no evidence of metastasis, then the three serial sections were stained with a murine monoclonal anti-cytokeratin antibody (CAM 5.2). Metastatic deposits were classified as macrometastasis (> 2.0 mm), micrometastasis (0.2-2.0 mm) or isolated tumour cells (ITC, < 0.2 mm). Of the 216 patients, 56 (26%) had metastasis as identified by H&E. Immunohistochemistry detected metastatic deposits in a further nine patients (4%), of whom four (2%) had micrometastasis and five (2%) had ITC only. Those cases with micrometastases were all, on review, visible on the H&E sections. Immunohistochemistry detects only a small proportion of metastasis in SLNs. All metastatic deposits identified by IHC were either micrometastasis or ITC. Until the prognostic significance of these deposits has been determined, IHC may be of limited value in the histopathological examination of SLNs.

Touch imprint cytology of core needle biopsy specimens: a useful method for immediate reporting of symptomatic breast lesions.

AIMS: The aim of this study was to determine the diagnostic value and accuracy of touch imprint cytology (TIC) of core needle biopsy (CNB) specimens in predicting the final benign or malignant histology in patients presenting with symptomatic breast lesions. METHODS: One hundred and twenty-eight patients underwent CNB under ultrasonographic guidance with subsequent TIC preparation. TIC results were correlated with the histology of the core or the surgical resection specimen. RESULTS: The 128 lesions analysed included 106 malignancies and 22 benign lesions. TIC accurately predicted the final histology in 96.7% of cases, with a sensitivity of 96.2% and a specificity of 100%. CONCLUSIONS: The routine use of TIC to complement CNB can provide an immediate and reliable cytological diagnosis of symptomatic breast lesions. The potential use of this technique in a breast clinic setting may help allay patient anxiety and expedite the planning of further surgical management.