Molecular endocrine pathology – Christofer Juhlin's Group

The research aims to identify key molecular and mutational events in thyroid, adrenal and other endocrine tumors, and their clinical applications in endocrine pathology and molecular pathology for improved decisions in diagnosis, prognosis and treatment.

Part of the:
Decorative histological image of a tumor.

Our research

We focus on delivering improved diagnostic and prognostic tools for tumors derived from endocrine tissues such as the thyroid and parathyroid glands in the neck as well as for abdominal neoplasias such as adrenal and neuroendocrine tumors. By utilizing modern genetic, epigenetic and proteomic methods together with conventional light microscopy and histopathology, candidate markers will be applied on clinical tumor material for the improved recognition of malignant disease and poorer patient outcome. Furthermore, the physiology of normal and hyperfunctioning endocrine glands is also studied. 

Our studies are supported by access to one of the largest biobanks of endocrine tumors, cutting-edge sequencing and imaging technologies, and a strong clinical network. Through these efforts, we seek to refine classification systems, improve patient stratification, and ultimately identify new molecular targets for therapy, thereby advancing precision medicine in endocrine pathology. The ventures are systematized as continuing cooperation projects with researchers at Karolinska Institutet, as well as the endocrine surgery division at the Karolinska University Hospital in Solna and multiple national and international collaborators.

Publications

All publications from group members

Funding

Grants

  • Swedish Cancer Society
    1 January 2024
    Thyroid cancer is becoming increasingly common in Sweden, and every year between 600-700 Swedes receive this diagnosis. Most patients are treated with surgery, and many patients subsequently receive radioactive iodine. There are different forms of thyroid cancer and the prognosis is mostly very good. However, a subgroup of patients suffer from relapse and distant spread - and here, in some cases, there is a lack of effective treatment. Today we know a number of genetic and microscopic risk factors that are linked to poorer prognosis, but we do not know exactly what it is that causes these molecular abnormalities to lead to serious disease. We want to overcome this problem. In the project, a number of different subgroups of thyroid cancer will be studied in detail with regard to molecular patterns to enable improved diagnostics, prognostics and treatment. We will analyze thyroid tumors from patients who have undergone surgery at Karolinska University Hospital in Solna, where we save tissue in connection with the performed surgery if the patient has previously given his consent to this. We want to identify protein patterns in thyroid cancer with established high-risk mutations, i.e. tumors with an increased risk of recurrence and spread. These proteins will then be mapped to try to develop markers for prognostication in clinical routine, and proteins with a clear link to existing, tailored treatment will be studied in detail. In addition, we want to map completely new gene mutations with unclear function, in order to evaluate how these affect tumor growth. Finally, we hope to identify molecules responsible for the cancer cells invading the tissue, with the goal of developing markers that gossip about spread.
  • Swedish Cancer Society
    1 January 2021
    Tumors in the thyroid gland are common, and the patient group is getting bigger every year - for reasons that are only partially known. The most common tumor form is called follicular tumors
    these are usually benign, but a malignant variant also occurs. Differentiating between these two forms is useless via biopsy, and thus all patients must be operated on for a diagnostic purpose. Another dilemma is that doctors do not always know how a malignant thyroid cancer should best be treated and followed up, as there is a partial lack of tools for how the tumors should be risk-assessed from a spread perspective. I want to introduce a molecular test into clinical use where small tissue biopsies from the thyroid gland are analyzed for a change (mutation) in the tumor's genetic material. This mutation indicates that a tumor has a significantly worse prognosis, and the hope is that the patient will receive a more adequate operation right from the start. Then I also want to introduce another test with an even broader analysis that is carried out once the tumor has been surgically removed, which also gives an indication of how serious the current tumor is. Finally, I am trying to find additional markers for the same purpose via a modern analysis of the tumor's genome. Cancer care cannot be conducted successfully without an accurate diagnosis
    knowing first of all which type of tumor to treat is the key to being able to cure a patient. My research tries to improve how we as doctors assess tumors in the thyroid gland and to implement the findings from the laboratory directly into everyday clinical practice. In this way, my research contributes to individualizing the assessment of these tumors, so that each individual patient can obtain an adequate prognosis based on a more high-resolution diagnosis than was previously possible to give.

The present research is generously supported by grants from:

  • The Swedish Cancer Society
  • Swedish Society for Medical Research (SSMF)
  • Stockholm county council
  • Karolinska Institutet
  • The Swedish Society of Medicine
  • The Cancer Research Foundations of Radiumhemmet
  • Lisa and Johan Grönberg foundation
  • Cancer and Allergy Fund

Staff and contact

Group leader

All members of the group

Previous team members

Adam Stenman, MD, PhD (Employment: Resident in Surgery, Karolinska University Hospital)
Nimrod Kiss, MSC, PhD
Na Wang, MD, PhD, Postdoc

Contact

Christofer Juhlin
Department of Oncololgy-Pathology, KI, Karolinska University Hospital-Solna BioClinicum J6:20; SE-171 64, Stockholm, Sweden
E-mail: Christofer.Juhlin@ki.se
Phone: +46-8 123 73930
Mobile: +46 739322988

Projects

Thyroid cancer – with focus on TERT dysregulation 

(Vincenzo Condello, Emmanouella Xanthopolou, Johan Paulsson, Samuel Hellgren, Martin Hysek, Kenbugul Jatta, Christofer Juhlin)

The project focuses on understanding TERT dysregulation in thyroid cancer and translating these findings into clinical applications. TERT promoter mutations are strongly associated with aggressive thyroid tumors, and their detection can serve as a prognostic marker. Our research aims to fully integrate preoperative TERT promoter mutational screening and postoperative TERT mRNA in situ hybridization into clinical routines to enhance diagnostic precision. Additionally, we investigate the nuclear-specific roles of TERT mRNA, exploring potential non-canonical functions that may influence tumor progression. A complementary aspect of this work involves global proteomic analysis to identify protein markers that can distinguish TERT-aberrant tumors and reveal potential therapeutic targets. The overarching goal is to refine risk stratification in thyroid cancer and identify novel diagnostic and prognostic markers that can be implemented in routine pathology. The findings from these studies could ultimately improve patient outcomes by guiding more precise treatment strategies, particularly for cases resistant to conventional therapies.

Thyroid cancer – dedifferentiation and radioiodine resistance 

(Vincenzo Condello, Emmanouella Xanthopolou, Johan Paulsson, Christofer Juhlin)

Our research focuses on unraveling the molecular mechanisms underlying thyroid cancer progression and dedifferentiation, aiming to improve diagnosis, prognostication, and therapeutic strategies. While well-differentiated thyroid cancers (WDTC) generally have favorable outcomes, dedifferentiation into poorly differentiated (PDTC) and anaplastic thyroid carcinoma (ATC) is associated with resistance to conventional treatments and a dismal prognosis. We investigate genetic and epigenetic drivers of this transformation, with a particular emphasis on TERT promoter mutations, microRNA regulators such as DGCR8, and other transcriptional alterations linked to loss of iodine avidity. A key project explores ANO1 as a novel biomarker for radioiodine-refractory (RAI-R) thyroid tumors, assessing its potential role in predicting RAI responsiveness and exploring strategies to restore iodine uptake. Additionally, single-cell RNA sequencing and spatial transcriptomics will be employed to trace the evolutionary trajectories of dedifferentiation, providing unprecedented insight into the transition from WDTC to ATC. Further, we are investigating the functional impact of DGCR8 mutations, which may contribute to aggressive thyroid tumor behavior, as well as the nuclear escape mechanisms of TERT mRNA, potentially revealing new vulnerabilities for therapeutic intervention. Supported by cutting-edge sequencing and bioinformatics resources at SciLifeLab and leveraging our extensive biobank of thyroid cancer specimens, our research aims to bridge molecular discoveries with clinical application, advancing precision oncology for aggressive thyroid cancers.

Neuroendocrine neoplasia 

(Zandra Ankers, Samuel Hellgren, Christofer Juhlin)

Our research aims to unravel the histological and molecular landscape of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), with a particular focus on distinguishing well-differentiated NET G3 tumors from poorly differentiated neuroendocrine carcinomas (NECs). Given the recent reclassification of these high-grade tumors, there is an urgent need to refine diagnostic criteria and improve prognostic accuracy. We will characterize the clinical, morphological, and molecular features of NET G3 and NECs, utilizing extensive patient cohorts from Karolinska University Hospital. By evaluating immunohistochemical markers, including TP53 and RB1, we aim to enhance diagnostic precision and establish new pathology-based classifiers. Additionally, we will explore the value of next-generation sequencing and PD-L1 expression as potential theranostic tools, assessing their role in guiding targeted therapies. Beyond genetic alterations, our research extends to epigenetic profiling using DNA methylation assays to uncover key regulatory changes influencing tumor progression. 

Adrenal neoplasia 

(Christofer Juhlin in collaboration with group S. Schlisio and group C. Larsson, Dept. of Oncology-Pathology)

These research projects include single-cell sequencing and paired spatial transcriptomics analyses of pheochromocytoma and paraganglioma to unveil tumor heterogeneity and cells of origin, in order to help identify clinical markers suitable for prognostication of these enigmatic tumors. Projects regarding clinical implementation of CYP11B2 as screening markers for primary aldosteronism are also included.

News

Keywords:
Adrenal Cortex Diseases Adrenal Cortex Neoplasms Adrenal Medulla Cancer and Oncology Carcinoma, Neuroendocrine Show all
Content reviewer:
Christofer Juhlin
Erika Rindsjö
25-09-2025