Analysis of Spatial Distribution and Prognostic Value of Different Pan Cytokeratin Immunostaining Intensities in Breast Tumor Tissue Sections

International Journal of Molecular Sciences

Velicko Vranes¹  Nemanja Rajković²  NebojšaT. Milošević²  Tijana Vujasinović³  Ksenija Kanjer³  Marko Radulovic³ 

[1] Department of Basic and Environmental Science, Instituto Tecnológico de Santo Domingo (INTEC), Santo Domingo 10602, Dominican Republic;Department of Biophysics, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia;Department of Experimental Oncology, Institute for Oncology and Radiology, 11000 Belgrade, Serbia;

关键词: breast cancer;    prognosis;    metastasis;    image analysis;    pan cytokeratin;    histopathology;   

DOI  :  10.3390/ijms21124434

来源: DOAJ

【 摘 要 】

Cancer risk prognosis could improve patient survival through early personalized treatment decisions. This is the first systematic analysis of the spatial and prognostic distribution of different pan cytokeratin immunostaining intensities in breast tumors. The prognostic model included 102 breast carcinoma patients, with distant metastasis occurrence as the endpoint. We segmented the full intensity range (0–255) of pan cytokeratin digitized immunostaining into seven discrete narrow grey level ranges: 0–130, 130–160, 160–180, 180–200, 200–220, 220–240, and 240–255. These images were subsequently examined by 33 major (GLCM), fractal and first-order statistics computational analysis features. Interestingly, while moderate intensities were strongly associated with metastasis outcome, high intensities of pan cytokeratin immunostaining provided no prognostic value even after an exhaustive computational analysis. The intense pan cytokeratin immunostaining was also relatively rare, suggesting the low differentiation state of epithelial cells. The observed variability in immunostaining intensities highlighted the intratumoral heterogeneity of the malignant cells and its association with a poor disease outcome. The prognostic importance of the moderate intensity range established by complex computational morphology analyses was supported by simple measurements of its immunostaining area which was associated with favorable disease outcome. This study reveals intratumoral heterogeneity of the pan cytokeratin immunostaining together with the prognostic evaluation and spatial distribution of its discrete intensities.

【 授权许可】

Unknown