Lymphangiogenesis and carcinoma in the uterine cervix: Joint and hierarchical models for random cluster sizes and continuous outcomes

摘要

Although the lymphatic system is clearly linked to the metastasis of mosthuman carcinomas, the mechanisms by which lymphangiogenesis occurs in responseto the presence of carcinoma remain unclear. Hierarchical models are presentedto investigate the properties of lymphatic vessel production in 2997 fieldstaken from 20 individuals with invasive carcinoma, 21 individuals with cervicalintraepithelial neoplasia and 21 controls. Such data demonstrate a high degreeof correlation within tumour samples from the same individual. Jointhierarchical models utilising shared random effects are discussed and fitted ina Bayesian framework to allow for the correlation between two key outcomemeasures: a random cluster size (the number of lymphatic vessels in a tissuesample) and a continuous outcome (vessel size). Results show that invasivecarcinoma samples are associated with increased production of smaller and moreirregularly-shaped lymphatic vessels and suggest a mechanistic link betweencarcinoma of the cervix and lymphangiogenesis.