Abstract C148: Expression and activation of p38 in papillary thyroid carcinoma.
Authors: Lamba Saini Monika , Weynand Birgit , Rahier Jacques , Mourad Michel , Hamoir Marc , Marbaix Etienne 
Published: August 2014

Introduction: Papillary thyroid cancer (PTC) is the commonest endocrine malignancy. PTC frequently carries several alterations in genes coding for proteins that activate the mitogen-activated protein kinase (MAPK) signaling pathway, which plays a key role in the regulation of cell growth, differentiation, and survival. The present study aims to investigate the MAPK signal transduction pathway [extracellular-regulated kinase (ERK), Jun N-terminal Kinase (JNK) and p38] involved in tumorigenesis of PTC.

Experimental procedures: Twenty samples of PTC and its follicular variant (11 classic PTC, 9 follicular variant of PTC) were retrieved from the UCL biolibrary. Corresponding paraffin blocks were selected for immunohistochemical analysis of total and phosphorylated forms of ERK, JNK and p38. Percentage of immunolabeled cells in tumors was graded as: slight staining in less than 10% of tumor cells; mild staining in 10-30%; moderate staining in 30-50% and abundant staining in more than 50 % of tumor cells. In addition, frozen sections of the same tumors were solubilized to perform Western blots of total and phosphorylated p38.

Results: ERK activation was seen as nuclear immunolabeling in 15/ 20 PTC cases in less than 10% of tumor cells. JNK activation was seen in 7/20 cases in less than 10% of tumor cells as nuclear and membranous immunolabeling. However, total ERK and total JNK was seen as nuclear and cytoplasmic immunolabeling in 10/20 and 16/20 cases respectively in more than 50% of tumor cells. p38 MAPK phosphorylation was seen as abundant nuclear and cytoplasmic immunolabeling in 11/20 cases (6 follicular variants of PTC and 5 classic PTC). Total p38 was immunolabeled in 14/20 cases. A one-way ANOVA test showed significant difference between the ERK, JNK and p38 phosphorylation (p&lt;0.01).

By Western blotting, p38 was detected in all twenty PTC samples and its phosphorylated form was detected in 17/20 samples. The signals were much stronger in the follicular variants of PTC as compared to classic PTC. p38 was also detected in normal thyroid tissue but not its phosphorylated form.

Conclusions: There is variable expression and activation of the MAPK pathways in PTC but p38 appears to be activated in a larger proportion of PTC than ERK or JNK. The role of p38 in tumorigenesis of PTC and its variable expression in different variants of PTC will be further investigated. The molecular profiling of PTC should help to better understand the altered biological pathways involved in the genesis of this cancer.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C148.

Citation Format: Monika Lamba Saini, Birgit Weynand, Jacques Rahier, Michel Mourad, Marc Hamoir, Etienne Marbaix. Expression and activation of p38 in papillary thyroid carcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C148.