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Verena Bröcker: Understanding rejection after uterus transplantation

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There has been a lack of understanding regarding rejection after uterus transplants. Verena Bröcker’s doctoral thesis delves into the microscopic and molecular aspects of rejection. The research findings could aid in tailoring crucial immunosuppressive treatments for uterus transplant recipients.

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Verena Bröcker is a subspecialized pathologist at Sahlgrenska University Hospital and is currently pursuing her doctorate at the Institute of Clinical Sciences.

VERENA BRÖCKER
Dissertation defense: 23 May 2024 (click for details)
Doctoral thesis: Histopathological characteristics and diagnosis of rejection in human uterus transplants
Research area: Obstetrics and Gynecology
Sahlgrenska Academy, The Institute of Clinical Sciences

In all transplanted organs, rejection is diagnosed through small tissue biopsies that require examination by a specialized pathologist. However, until now, it has been unclear how rejection in transplanted uteruses appears under the microscope and what criteria should be used to diagnose it.

“A correct diagnosis is crucial for managing the immunosuppressive treatment that all organ recipients need as effectively as possible. Too much immunosuppressive treatment can lead to life-threatening side effects. Insufficient treatment can result in the loss of the transplanted organ,” explains Verena Bröcker, a specialized pathologist at Sahlgrenska University Hospital, pursuing her doctoral studies at the Institute of Clinical Sciences.

Cover image of the thesis. The figure shows a microscopic picture from the cervix of a transplanted uterus, as well as immunohistochemistry for T-cells and details from a heatmap of differentially expressed genes in uterus transplants.

Grading system for diagnosis

What is your research about, in brief?
“My thesis focuses on describing how rejection in transplanted uteruses appears under the microscope and also molecularly, and how to diagnose rejection using small tissue biopsies.”

What are the key research findings?
“In a first step, we proposed a grading system for diagnosing rejection in transplanted uteruses, based on findings from previous animal studies and biopsies from the first transplanted women in Gothenburg. An important result from the initial two studies was also that biopsies from the uterine cervix, which are easily accessible and can be taken without major risks to the organ recipient or fetus, are useful for diagnosing rejection,” says Verena Bröcker, adding:

“We could then demonstrate that the grading system for rejection was reproducible when different pathologists independently examined the same biopsies. Analyses of gene expression in the biopsies corresponded well with the histological grading system.”

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Figure 2, page 17. Schematic illustration of the histopathological grading scheme for diagnosis of rejection in human uterus transplant cervical biopsies, as proposed in paper I. (Copyright Elsevier, with permission). See detailed caption below.

“A more standardized treatment”

What significance can this research have?
“By systematically studying the microscopic and molecular picture in biopsies from transplanted uteruses, we have been able to create a histological grading system for diagnosing rejection. This can be used by other pathologists worldwide who need to assess rejection in uterus transplants. This makes the diagnosis and thus the treatment more standardized, and results from clinical studies from different countries can be compared.”

”Pathology that none seen before

What has been enjoyable and rewarding about the doctoral project?
“It’s very rare for a pathologist to have the opportunity to observe and describe pathology that no one has ever seen before. That has been the most enjoyable aspect of my particular research niche. Additionally, I am very grateful for the opportunity to learn new things in various challenging areas such as statistics, interpretation of molecular data, and writing scientific articles. There are many excellent courses to choose from,” says Verena Bröcker.

And what has been the biggest challenge?
“Dealing with the anxiety about whether everything I have done is truly accurate when it finally comes to publication, that has been the biggest challenge for me.”

Text: Jakob Lundberg

Detailed caption for figure 2

Schematic illustration of the histopathological grading scheme for diagnosis of rejection in human uterus transplant cervical biopsies, as proposed in paper I. a) normal tissue, b) borderline-changes (inflammation of uncertain significance between normal and mild rejection), c) mild rejection, d) moderate rejection, e) severe rejection (adapted from: Figure 2 in Mölne et al. American Journal of Transplantation 2017; 17:1628–1636, Copyright Elsevier, with permission.)