Isolated tumour cells and micrometastases in axillary sentinel nodes carry a low risk of non-sentinel node metastasis. The risk of metastasis to further echelon nodes is higher with macrometastases, especially if there is extracapsular growth and the proportion of involved sentinel nodes is high.

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KeywordsPseudoxanthoma elasticum; presymptomatic testing; mutation analysis Sir, Pseudoxanthoma elasticum (PXE) is a multi-system disorder characterized by ectopic mineralization of extracellular matrix of connective tissues (For review, see ref 1). The disease primarily affects the skin, the eyes, and the cardiovascular system, with considerable mortality and occasional morbidity. The characteristic skin manifestations, i.e., yellowish papules, which tend to coalesce into larger inelastic plaques on the predilection sites, are primarily of cosmetic concern, but they imply the risk for development of serious ocular and vascular complications.PXE is caused by mutations in the ABCC6 gene which encodes transmembrane transporter expressed primarily in the liver and kidneys2. The precise function of this transporter under physiologic conditions and its ligand molecules in vivo are currently unknown. It has been suggested, however, largely based on animal studies utilizing an Abcc6 "knock-out" mouse as a model system, that PXE is a metabolic disorder which in the absence of functional ABCC6 transporter activity results in deficiency of anti-mineralization factors in the circulation3. This situation then allows progressive mineralization of the peripheral connective tissues to ensue.Well over 300 mutant ABCC6 alleles have been identified in families with PXE, and mutation analysis has established that PXE is an autosomal recessive disorder4,5. The utility of mutation detection in PXE is emphasized by the fact that the onset of the disease is delayed, and definitive diagnosis in patients with PXE is often not established until late

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