The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma.

The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. ≤3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.

Herd behavior in designer genes.

The ability of individuals to choose their children's genes has increased over time and may ultimately culminate in a world involving free market reprogenetic technologies. Reprogenetic technologies combine advances in reproductive biology and genetics to provide humans increased control over their children's genes. This Article offers economic perspectives that are helpful in understanding the possibly unexpected ethical, legal, and social issues at stake in using reprogenetic technologies for trait enhancement selection. The Appendix analyzes two competitive games that might arise in such a biotechnological society. Specifically, the Article focuses on herd behavior, caused by either a popularity contest or positional competition, in the choice of genetic traits. The analytical game-theoretic models in the Appendix can have several equilibrium outcomes in terms of individual reprogenetic technological choices and corresponding beliefs about such choices by others. This multiplicity of potential social outcomes suggests that a society can attain efficiency if the state or some private organization transforms individual parents' beliefs over the choices of other parents regarding their children's traits and, thus, coordinates parental reprogenetic decisions by selecting, as focal, certain beliefs over parents' reprogenetic decisions.