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

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

Christofer Juhlin is holding the 5th edition of the WHO classification of endocrine and neuroendocrine tumors.
Christofer Juhlin. Photo: N/A

The 5th edition of the World Health Organization (WHO) Classification of Endocrine and Neuroendocrine Tumors has now been officially published in print. This highly anticipated reference work is widely regarded as the global gold standard for tumor diagnosis, offering a comprehensive synthesis of traditional histopathology with cutting-edge digital and molecular pathology. 

Dr. Christofer Juhlin, Associate Professor and group leader at the Department of Oncology-Pathology, Karolinska Institutet, has contributed as co-author of 13 chapters focusing on tumors of the thyroid, parathyroid, and adrenal glands. The WHO classification series is used by pathologists, oncologists, and researchers worldwide, guiding diagnostic criteria and serving as a cornerstone for clinical decision-making and cancer research. Dr. Juhlin’s contributions further underscore our group’s commitment to endocrine pathology and improving therapeutic accuracy in endocrine oncology.