Slide-free virtual histochemistry (Part II): detection of field cancerization

Tumor-adjacent "normal" tissue constitutes a peri-tumoral field that affects early cancer detection, risk assessment, surgical decision, and postoperative surveillance. Modern genetic analysis has revealed valuable information from this field, but without the spatial resolution of optical microscopy to understand the vital microenvironments that surround individual cells. Rapidly advanced optical imaging techniques free of labor-intensive sample preparation, despite great promise to perform slide-free imaging of cell structure and shift the histology-centered cancer diagnostic paradigm, have lacked compatible and complementary histochemical imaging of cell function or phenotype to interrogate the peri-tumoral field. In the first part (Part I) of this two-part series study, we developed a technique of slide-free virtual histochemistry to phenotype various cells in in vivo animal and ex vivo human tissue. Here, in the second part (Part II) of this two-part series study, we employ this technique to examine various peri-tumoral fields and produce the volumetric histochemical evidence of field cancerization consistent with the structural changes at larger spatial scales. We also link the field cancerization with cancer dormancy in a significant portion of breast cancer patients.