Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging.
Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial-connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, "ECTI contour," is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo Cancer Res; 76(16); 4637-47. ©2016 AACR.
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas. rapal@utmb.edu.
Rahul
R
Pal
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas.
Tuya
T
Shilagard
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas.
Jinping
J
Yang
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas.
Paula
P
Villarreal
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas.
Tyra
T
Brown
Department of Pathology, The University of Texas Medical Branch, Galveston, Texas. Center for Cancers of the Head and Neck, The University of Texas Medical Branch, Galveston, Texas.
Suimin
S
Qiu
Center for Cancers of the Head and Neck, The University of Texas Medical Branch, Galveston, Texas. Department of Otolaryngology, The University of Texas Medical Branch, Galveston, Texas.
Susan
S
McCammon
Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas. Center for Cancers of the Head and Neck, The University of Texas Medical Branch, Galveston, Texas. Department of Otolaryngology, The University of Texas Medical Branch, Galveston, Texas.
Vicente
V
Resto
Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, Texas. Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas.
Gracie
G
Vargas
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D019540:Area Under Curve; D002273:Carcinogens / Q000633:toxicity; D003238:Connective Tissue / Q000000981:diagnostic imaging*; D006224:Cricetinae; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D008647:Mesocricetus; D008853:Microscopy / Q000379:methods; D009061:Mouth Mucosa / Q000000981:diagnostic imaging*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000000981:diagnostic imaging*; D012372:ROC Curve; D012680:Sensitivity and Specificity
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene