Search

Head and neck squamous cell carcinoma (HNSCC) is a heterogenous disease where, in advanced stages, clinical and pathological stages do not correlate with outcome. Molecular and genomic biomarkers for HNSCC classification have shown promise for prognostic and therapeutic applications. In this study, we utilize automated image analysis techniques in whole slide images of HNSCC tumors to identify relationships between cytometric features and genomic phenotypes. Hematoxylin and eosin-stained slides of HNSCC tumors (N = 49) were obtained from the Cancer Imaging Archive (TCIA), along with accompanying clinical, pathological, genomic, and proteomic reports. Automated nuclear detection was performed across the entirety of slides, and cytometric feature maps were generated. Forty-one cytometric features were evaluated for associations with tumor grade, tumor stage, tumor subsite, and integrated genomic subtype (IGS). Thirty-two features demonstrated significant association with IGS when corrected for multiple comparisons. In particular, the basal subtype was visually distinguishable from the chromosomal instability and immune subtypes based on cytometric feature measurements. No features were significantly associated with tumor grade, stage, or subsite. This study provides preliminary evidence that features derived from tissue pathology slides could provide insights into genomic phenotypes of HNSCC.

Additional file 1: Figure S1. CD45 + lymphocytes within the tumor microenvironment of OPSCC. A population of CD14 + lymphocytes are seen representing cells of hematopoietic lineage (A-C). The black box denotes areas visualized under higher power magnification. The above photomicrographs are serial sectios (4 μm thickness).

Additional file 2: Figure S2. IgG negative controls at 20Ă magnification. The above photomicrographs are serial sections (4Â Îźm thickness).

Additional file 6: Figure S7. Using the preliminary screening data, ELISA assays were conducted on SDF-1ι, VEGF, Gro-ι, IL-8, IL-6, and PDGF with the addition of CXCL7 to confirm the observations made in Additional file 1: Figure S6.

Additional file 3: Figure S4. The MSC markers gremlin-1 and CD105 are co-localized in the TM of patient with OCSCC (oral tongue). High power resolution confocal images from representative sections of human OCSCC specimens (A) demonstrate TM cells positive for the MSC markers anti-gremlin-1 (red) and anti-CD105 (green). An orange color on merged images indicates co-localization of gremlin-1 and CD105. In addition, TM MSCs were detected by anti-gremlin-1 (red) and anti-CD90 (blue). A magenta color on merged images indicates co-localization of gremlin and CD90 that did not co-localize with the hematopoietic marker, anti-CD45 (green) (B). The nuclei are depicted as grey.

Additional file 2: Figure S2. IgG negative controls at 20Ă magnification. The above photomicrographs are serial sections (4Â Îźm thickness).

Additional file 3: Figure S4. The MSC markers gremlin-1 and CD105 are co-localized in the TM of patient with OCSCC (oral tongue). High power resolution confocal images from representative sections of human OCSCC specimens (A) demonstrate TM cells positive for the MSC markers anti-gremlin-1 (red) and anti-CD105 (green). An orange color on merged images indicates co-localization of gremlin-1 and CD105. In addition, TM MSCs were detected by anti-gremlin-1 (red) and anti-CD90 (blue). A magenta color on merged images indicates co-localization of gremlin and CD90 that did not co-localize with the hematopoietic marker, anti-CD45 (green) (B). The nuclei are depicted as grey.

Additional file 6: Figure S7. Using the preliminary screening data, ELISA assays were conducted on SDF-1ι, VEGF, Gro-ι, IL-8, IL-6, and PDGF with the addition of CXCL7 to confirm the observations made in Additional file 1: Figure S6.