3 D Reconstruction of Cervical Carcinoma Invasion Front using H&E/p16INK4a/CD3 Alternate Staining

Background In this present study, we aimed to analyze the spatial organization of a cervical cancer (CX) and the relation of the tumor invasion front and the infiltration with CD3 positive T-cells. Methods 84 serial sections from CX were stained with H&E and immunohistochemically against the cervical p16 and the T-cell marker CD3. Sections were passed through an image processing chain in order to obtain a reconstructed tissue volume including both automatically delineated tumor and T-cell volume segments. For invasion front analysis mean curvature was used, which in turn was related to the respective local minimum tumor to T-cell distance as well to a T-cell originated diffusing substancersquor;s concentration at the tumor surface. Results Spatial models of the tumor tissue and the infiltrating T-cells were computed. The overall discrete compactness of the tumor invasion front was 0.89, corresponding to a pathological assessment of diffuse infiltration. The comparison of the tumor invasion front with the density of T-cell infiltration revealed an increased smoothening in regions with high T-cell infiltration. Conclusions Results suggest the spatial organization of CX and model the interaction between infiltrating T-cells with the shape of CX at invasion front. T-cells may have an influence on the shaping of the tumor invasion front, e.g. by attacking tumor cells displaying specific antigens. The applied technique allows to visualize the spatial organization of tissues.

cancer - cervix - front of invasion - inflammatory response - tumor biology