Carine Maenhaut

Our research

Thyroid Cancer group – Research activities

Tumors originating from thyroid follicular cells are the most frequent endocrine tumors with an increasing incidence that will make this cancer one of the most common in women in the next decade. They comprise a spectrum of well-defined morphological phenotypes with variable rates of growth, differentiation and biological aggressiveness. They include benign follicular adenomas and malignant carcinomas, further subdivided in follicular (FTC) or papillary (PTC) carcinomas, still partly differentiated. Both of which may evolve in anaplastic carcinoma (ATC), totally dedifferentiated. While PTC (85 % of the thyroid cancers) and FTC have a relatively good prognosis and can mostly be treated with surgery and I131, ATC are lethal within six months and do not respond to any therapy (surgery, chemotherapy, I131). ATC are responsible for half of the thyroid cancer related deaths and are one of the most aggressive cancers. They are representative of finally evolving cancers in general.
Among the very common thyroid nodules (up to 40% beyond 50 years), only 5% are found to be malignant. Fine-needle aspiration (FNA) is routinely used in the preoperative evaluation of these nodules. However, 15% to 30% of aspirations yield inconclusive cytological findings. Many patients therefore are operated, three out of four unnecessarily.
The clinical evolution of thyroid tumors thus varies extremely according to their type, and a reliable diagnosis for the various sub-types of tumors to select adequate treatments as well as new therapeutic tools are highly required.

Figure: Thyroid tumorigenesis, altered signaling pathways and main mutations

Since several years, first by using microarrays and now by performing next generation sequencing, we are defining the molecular profiles of the different types of thyroid tumors.
Among the molecular markers investigated to improve diagnosis and to establish new therapies, miRNA seem promising. Our recent miRNA profiling in papillary thyroid carcinomas has led to the identification of miRNA differentially expressed between normal thyroid, PTC and lymph node metastases with potential diagnostic application. From these data and the literature, we have identified a potential miRNA signature allowing to discriminate malignant from benign thyroid tissues. One of our current research aims is to evaluate the diagnostic potential of this new miRNA signature for thyroid cancer detection on pre-operative fine needle biopsies, and to correlate miRNA expression and tumor histology. This signature will help to decide whether to refer to surgery or not.
We are also focused on the role of miRNA in thyroid tumor progression, and more specifically in the transition from slowly developing thyroid cancers (papillary or follicular thyroid carcinomas) to aggressive anaplastic thyroid cancers.
Another objective of our work is to better understand tumor progression by defining the relative contribution of tumor and stromal cells to thyroid tumorigenesis, i.e. to study tumor heterogeneity at the single cell level. We are currently developing and optimizing single cell sequencing and spatial transcriptomics for papillary and anaplastic thyroid cancers, in order to get a picture of the multiple cell types in the cancer tissue.

Group members

Carine Maenhaut, PI (cmaenhau@ulb.ac.be)

Phone # +32 (0)2 555 4137

Postdocs

Geneviève Dom
Manuel Saiselet
Aurélie Strickaert

PhD students

Alice Augenlicht
Olivier Hancisse

Technical Support

Chantal Degraef

Publications

Selected publications

Wattel S., Mircescu H., Venet, D., Burniat A., Franc, B., Frank S., Andry, G., Van Sande J., Rocmans P., Dumont J.E., Detours V., Maenhaut C. (2005) Gene expression in thyroid autonomous adenomas provides insight into their physiopathology. Oncogene 24, 6902-6916.

van Staveren W., Weiss D., Delys, L., Venet D., Cappello M., Andry G., Dumont J.E., Libert F., Detours V., Maenhaut C. (2006) Gene expression in human thyrocytes and autonomous adenomas reveals suppression of negative feedbacks in tumorigenesis. Proc. Natl. Acad. Sci, 103, 413-418.

Delys L., Detours V., Franc, B., Thomas G., Bogdanova T., Tronko M., Libert F., Dumont J.E., Maenhaut C. (2007) Gene expression and the biological phenotype of papillary thyroid carcinomas. Oncogene 26, 7894-7903.

Detours V., Delys L., Libert F., Weiss Solis D., Bogdanova T., Dumont J.E., Franc B., Thomas G., Maenhaut C. (2007) Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers. Br. J.Cancer 97, 818-825.

van Staveren W., Weiss D., Delys L., Duprez L., Andry, G., Franc B., Thomas G., Libert F., Dumont J.E., Detours V., Maenhaut C. (2007) Human thyroid tumor cell lines derived from different tumor types present a common dedifferentiated phenotype. Cancer Research 67, 8113-8120.

van Staveren W., Weiss D., Hebrant A., Detours V., Dumont J.E., Maenhaut C. (2009) Human cancer cell lines: experimental models for cancer cells in situ? For cancer stem cells? BBA – reviews on cancer 1795, 92-103.

Hebrant A., Van Sande J., Roger P., Patey M., Klein M., Bournaud C., Savagner F., Leclere J., Dumont J.E., van Staveren, W., Maenhaut C. (2009) Thyroid gene expression in familial non-autoimmune hyperthyroidism shows common characteristics with hyperfunctioning autonomous adenomas. J Clin Endocrinol Metab. 94, 2602-2609.

Dom G., Tarabichi M., Unger K., Thomas G., Oczko-Wojciechowska M., Bogdanova T., Jarzab B., Dumont J.E., Detours V., Maenhaut C. (2012) A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas. Br. J. Cancer 107, 994-1000.

Hebrant A., Dom G., Dewaele M., Andry G., Trésallet C., Leteurtre E., Dumont J.E., Maenhaut C. (2012) mRNA expression in papillary and anaplastic thyroid carcinoma: molecular anatomy of a killing switch. PLOS ONE 7 (10), e37807.

Hebrant A., Floor S., Saiselet M., Antoniou A., Desbuleux A., Snyers B., La C., de Saint Aubain N., Leteurtre E., Andry G., Maenhaut C. (2014) miRNA expression in anaplastic thyroid carcinomas. PLOS ONE 9 (8), e103871.

Floor S., Hebrant A., Pita J., Saiselet M., Trésallet C., Libert F., Andry G., Dumont J.E., van Staveren W., Maenhaut C. (2014) miRNA expression may account for chronic but not for acute regulation of mRNA expression in human thyroid tumor models. PLOS ONE, 9 (11), e111581.

Le Pennec S., Konopka T., Gacquer D., Fimereli D., Tarabichi M., Tomás G., Savagner F., Decaussin-Petrucci M., Trésallet C., Andry G., Larsimont D., Detours V., Maenhaut C. (2015) Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases. Endocrine Related Cancer 22, 205-216.

Floor S., Trésallet C., Hébrant A., Desbuleux A., Libert F., Hoang C., Capello M., Andry G., van Staveren W., Maenhaut C. (2015) microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation. Molecular and Cellular Endocrinology 411, 1-10.

Saiselet M., Gacquer D., Spinette A., Craciun L., Decaussin-Petrucci M., Andry G., Detours V., Maenhaut C. (2015) New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer. BMC Genomics 16, 828.

Dom G., Frank S., Floor S., Kehagias P., Libert F., Hoang C., Andry G., Spinette A., Craciun L., de Saint Aubin N., Tresallet C., Tissier F., Savagner F., Majjaj S., Gutierrez-Roelens I., Marbaix E., Dumont J.E., Maenhaut C. (2018) Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution. Oncotarget 9, 10343-10359.

Tarabichi M., Antoniou A., Le Pennec S., Gacquer D., de Saint Aubain N., Craciun L., Cielen T., Laios I., Larsimont D., Andry G., Dumont J.E., Maenhaut C., Detours V. (2018) Distinctive desmoplastic 3D morphology associated with BRAFV600E in papillary thyroid cancers. J Clin Endocrinol Metab., Jan 12. doi: 10.1210/jc.2017-02279. (C. Maenhaut and V. Detours contributed equally).