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

TL;DR

This study uses joint hierarchical Bayesian models to analyze lymphangiogenesis in cervical carcinoma, revealing increased production of smaller, irregular lymphatic vessels associated with invasive carcinoma.

Contribution

It introduces joint hierarchical Bayesian models to analyze correlated outcomes in lymphangiogenesis, accounting for cluster size and vessel size in cervical cancer tissues.

Findings

Invasive carcinoma correlates with increased lymphatic vessel production.

Carcinoma samples show smaller, irregular lymphatic vessels.

High correlation within tumor samples from the same individual.

Abstract

Although the lymphatic system is clearly linked to the metastasis of most human carcinomas, the mechanisms by which lymphangiogenesis occurs in response to the presence of carcinoma remain unclear. Hierarchical models are presented to investigate the properties of lymphatic vessel production in 2997 fields taken from 20 individuals with invasive carcinoma, 21 individuals with cervical intraepithelial neoplasia and 21 controls. Such data demonstrate a high degree of correlation within tumour samples from the same individual. Joint hierarchical models utilising shared random effects are discussed and fitted in a Bayesian framework to allow for the correlation between two key outcome measures: a random cluster size (the number of lymphatic vessels in a tissue sample) and a continuous outcome (vessel size). Results show that invasive carcinoma samples are associated with increased production of smaller and more irregularly-shaped lymphatic vessels and suggest a mechanistic link between carcinoma of the cervix and lymphangiogenesis.