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There are practical difficulties relating to assessing lymph node number if nodal fragments rather than whole nodes are delivered to pathology. There is also evidence that inadequate pathological examination may underestimate the degree of nodal involvement [21]?and?[22]. Does the degree of nodal involvement matter? Although it is traditionally taught that extracapsular spread of tumour from mediastinal nodes is a poor prognostic factor, some studies have failed to demonstrate a survival disadvantage [23], raising the possibility that this opinion is probably based on assumption rather than on hard data, especially since such spread may render the disease unresectable, rendering information incomplete. There has been considerably more debate regarding the significance of micrometastatic disease in lymph nodes in patients bepotastine with surgically resected NSCLC. The fact that a proportion of patients with pStage I (N0) disease relapse and die of tumour recurrence fuels a presumption of undetected micrometastatic disease at the time of surgery. Micrometastatic disease has no clear definition in the context selleck chemicals llc of lung cancer, unlike in some other tumours such as breast cancer where nodal tumour deposits of Olaparib purchase to be sufficiently specific and sensitive to detect metastases of any size. The outcome of these studies will depend on the adequacy of the ��standard�� H&E-based initial assessment which determined N0 status. None of the IHC markers used is specific for tumour cells, and benign intra-nodal inclusions present the risk of a false-positive test. The same lack of specificity applies to most (possibly all) of the mRNA-based studies, although more recent work has used markers which are more specific [27]. Other issues with PCR studies include the following: ? The presence of mRNA does not necessarily mean that tumour cells are present, only that macromolecules have been detected. Whatever the pros and cons of the technical approach, it is the outcome that ultimately matters.