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Biology subjects

Solis Soto, L. M.

Publications and source records attributed to Solis Soto, L. M..

3 recordsLinked to original sources

Tissue Factor Expression in Penile Squamous Cell Carcinoma: A Marker of HPV-Independent Disease

In a series of 33-patients, we evaluated tissue factor (TF) expression in penile squamous cell carcinoma (PSCC). A tissue microarray (TMA) was constructed with 3 cores per patient tumor (99 total cores). Anti-TF antibody staining was performed by immunohistochemistry and H-scores for membrane and cytoplasm staining were assessed (range 0-300). Percentage of cores and patient tumors staining positive for TF ([&ge;]10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) and H-scores were described and compared with HPV and p16 status. Association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), aberrant p53 expression, recurrence free survival (RFS), and cancer specific survival (CSS) were assessed. Nectin-4 and TROP2 staining and their association with clinical/pathological data was determined in a similar manner. TF staining was more prominent in HPV-negative tumors in both the membrane (H-score 69.6 vs 18.8; p=0.003) and cytoplasm (H-score 59.2 vs. 17.7, p=0.007). Cytoplasmic (H-score 61.7 vs 11.7, p=<0.001) and membrane TF staining (H-score 71.7 vs 15.0, p=<0.001) favored p16 negative tumors. The p53 status was more likely to be aberrant in the higher TF staining samples (cytoplasm H-score 61.7 vs 18.3, p=0.012; membrane H-score 67.5 vs 20.3, p=0.006). We observed an association with TROP2 staining and positive p16 status (membrane H-score 120.3 vs. 85, p=0.052; cytoplasmic H-score 135 vs. 107.5, p=0.041). We observed an association of TROP2 staining with positive LVI (membrane H-score 136.7 vs. 66.7, p=0.014; cytoplasmic H-score 110 vs. 93.3, p=0.04). We found no association between TF, TROP2, or nectin-4 staining with CSS or RFS; however, we suspect that this is due to our small sample size. Our results indicate that TF expression could be positive biomarker for HPV-independent, p53-aberrant PSCC, while TROP2 could be associated with HPV-associated PSCC.

pathology↗

TLS_Finder: An algorithm for Identifying Tertiary Lymphoid Structures Using Immune Cell Spatial Coordinates

Tertiary lymphoid structures (TLS) are lymphoid formations that develop in non-lymphoid tissues during chronic inflammation, autoimmune diseases, and cancer. Accurate identification and quantification of TLS in tissue can provide crucial insights into the immune response of several disease processes including antitumor immune response. TLS are defined as aggregates of T cells, B cells and dendritic cells. In histological tissue sections stained with Hematoxylin and Eosin they are identified as aggregates of 50 or more lymphoid cells, however immunohistochemical analysis are required to confirm presence of distinct immune cell patterns. Assessment of lymphoid aggregates can be done in H&E slides or in slides stained with single or multiplex immunohistochemistry or other tissue based high-plex approaches with key biomarkers such as CD3 (T cells) and CD20 (B cells), however manual assessment of them is time consuming thus limiting its full evaluation. To our knowledge, published algorithms that identify TLS within a tissue are based on histological assessment of H&E slides or through use of ML algorithms trained on images that show the TLS presence in tissues; and quantification and spatial analysis of TLS still remains a challenge. This study aims to develop a robust algorithm to recognize TLS using the spatial coordinates of immune cells in any given tissue. The algorithm uses X and Y coordinates of T and B cells in tissues identified by a pathologist-supervised digital image analysis of multiplex chromogenic immunohistochemistry of tissues stained with CD3 and CD20. The algorithm is flexible to be used for detailed analysis of TLS stages; including other cell types within the definition of TLS; such as dendritic cells (DC) and high endothelial venules (HEV); to assess different stages of TLS formation.

bioinformatics↗

Comparison of imaging-based single-cell resolution spatial transcriptomics profiling platforms using formalin-fixed, paraffin-embedded tumor samples

Imaging-based spatial transcriptomics (ST) is evolving rapidly as a pivotal technology in studying the biology of tumors and their associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. In this study, we used serial 5-m sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma tumor samples in tissue microarrays to compare the performance of the single cell ST platforms CosMx, MERFISH, and Xenium (uni/multi-modal) platforms in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx Digital Spatial Profiler, and hematoxylin and eosin staining data for the same samples. In addition to objective assessment of automatic cell segmentation and phenotyping, we performed pixel-resolution manual evaluation of phenotyping to carry out pathologically meaningful comparison between ST platforms. Our study detailed the intricate differences between the ST platforms, revealed the importance of parameters such as tissue age and probe design in determining the data quality, and suggested reliable workflows for accurate spatial profiling and molecular discovery.

bioinformatics↗