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Aims: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. Methods: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. Results: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. Conclusions: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases . 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Summary Angiogenesis is recognized as an important step in tumour pathogenesis that is related to invasion and metastatic spread and which consequently results in poor clinical outcome. In this study, we have examined the role of tumour stroma-activated fibroblasts and macrophage infiltration in the development of the angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A total of 141 cases of early stage I-Il NSCLC treated with surgery alone were analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP) reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP overexpression related to high vascular grade and to advanced T stage (P = 0.0004 and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high angiogenesis (P = 0.01), but was independent of cancer cell expression. Fibroblast TP overexpression was related to abundant stroma (P = 0.003), suggesting that TP may be a marker of active stroma. Moreover, intense macrophage infiltration was associated with fibroblast TP reactivity, regardless of the amount of stroma, suggesting that macrophages may be a major contributor to TP expression in stroma. Survival analysis showed that cancer cell TP overexpression was related to poor prognosis (P = 0.005). Although stroma TP is related to angiogenesis, in the low vascular grade group it defined a group of patients with better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an indirect marker of tumour infiltration by functional macrophages, which have an antitumour effect. We conclude that stromal macrophage and fibroblast TP reactivity may have an important role in non-small-cell lung cancer behaviour. Understanding the role of stromal fibroblasts and inflammatory cells and their interaction with oncoprotein expression is essential for the elucidation of lung cancer pathogenesis.

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