Phenotypic Intratumoral Heterogeneity of Endometrial Carcinomas

Authors and Affiliations:
Cátia Silva MD ^1,2, Ana S. Pires-Luís MD ^3,4, Eduardo Rocha PhD ⁵, Carla Bartosch MD ^2,3,4, José M. Lopes MD PhD ^1,2,6

¹Department of Pathology, Centro Hospitalar São João, Porto, Portugal;

²Department of Pathology and Oncology, Medical Faculty, University of Porto, Portugal;

³Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal;

⁴Cancer Epigenetics & Biology Group, Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal;

⁵Department of Microscopy, Laboratory of Histology and Embryology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal;

⁶IPATIMUP (Institute of Molecular Pathology and Immunology, University of Porto) & I3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Portugal.

Abstract:
Intratumoral heterogeneity has been shown to play an important role in diagnostic accuracy, development of treatment resistance and prognosis of cancer patients. Recent studies have proposed quantitative measurement of phenotypic intratumoral heterogeneity, but no study is yet available in endometrial carcinomas. In our study we evaluated the phenotypic intratumoral heterogeneity of a consecutive series of ten endometrial carcinomas using measures of dispersion and diversity. Morphometric architectural [%tumor cells (%TC), %solid tumor (%ST), %differentiated tumor (%DT) and %lumens (%LUM)] and nuclear [volume-weighted mean nuclear volume (v ̅_V)] parameters, as well as ER, PR, p53, vimentin and beta-catenin immunoexpression (H-score) were digitally analyzed in twenty microscopic fields per carcinoma. Quantitative measures of intratumoral heterogeneity included coefficient of variation (CV) and relative quadratic entropy (rQE). In each endometrial carcinoma there was slight variation of architecture from field to field, resulting in globally low levels of heterogeneity measures (mean CV %TC:0.10, %ST:0.73, %DT:0.19, %LUM:0.61 and mean rQE %TC:18.5, %ST:20.3, %DT:25.6, %LUM:21.8). Nuclear intratumoral heterogeneity was also globally low (mean v ̅_V CV: 0.23 and rQE: 27.3), but significantly higher than the heterogeneity of architectural parameters within most carcinomas. In general, there was low to moderate variability of immunoexpression markers within each carcinoma, but ER (mean CV: 0.56 and rQE: 46.2) and PR (mean CV: 0.60 and rQE: 39.3) displayed the highest values of heterogeneity measures. Intratumoral heterogeneity of immunoexpression was significantly higher than that observed for morphometric parameters. Also, there were frequently positive correlations between heterogeneity of different immunoexpression markers. In conclusion, our study indicates that endometrial carcinomas present a variable but predominantly low degree of phenotypic intratumoral heterogeneity.

Journal: International Journal of Gynecological Pathology

Link: https://www.ncbi.nlm.nih.gov/pubmed/28582348