Abstract
The prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest. Characterization of the TME often relies on a small representative tissue sample. However, the adequacy of such a sample for assessing components of the TME is not yet known. Here, we used immunohistochemical (IHC) staining and 7-color multiplex staining to evaluate CD8 (cluster of differentiation 8), CD68, PD-L1 (programmed death-ligand 1), CD34, FAP (fibroblast activation protein), and cytokeratin in 220 tissue cores from 26 high-grade serous ovarian cancer samples. Comparisons were drawn between a larger tumor specimen and smaller core biopsies based on number and location (central tumor vs. peripheral tumor) of biopsies. Our analysis found that the correlation between marker-specific cell subsets in larger tumor versus smaller core was stronger with two core biopsies and was not further strengthened with additional biopsies. Moreover, this correlation was consistently strong regardless of whether the biopsy was taken at the center or at the periphery of the original tumor sample. These findings could have a substantial impact on longitudinal assessment for detection of biomarkers in clinical trials.
Highlights
The prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest
We have established a methodology www.nature.com/scientificreports to evaluate the TME components, providing a high-throughput protocol for clinical translation. This method benefits from the bioinformatics power of inForm Cell analysis and the use of multiplex IHC staining to identify differing cell populations
The use of multiplex staining is important since it allows for identification of specific individual cell populations in one tissue specimen
Summary
The prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest. Our analysis found that the correlation between marker-specific cell subsets in larger tumor versus smaller core was stronger with two core biopsies and was not further strengthened with additional biopsies This correlation was consistently strong regardless of whether the biopsy was taken at the center or at the periphery of the original tumor sample. Serial tumor biopsies have been applied to evaluate putative predictive biomarkers and to test for target-specific effects with novel therapies[12]. It is unclear whether serial biopsies adequately represent the heterogeneity of tumor specimens[13]. We found that TME components can be assessed reliably with a minimum of three small tissue biopsies taken at random locations within the larger tumor
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