C-Cells hyperplasia, what is their role in the development of sporadic medullary cancer?

Jacqueline Almeida; Virginia Cappagli; Valeria Bottici; Clara Ugolini; francesca signorini; Raffaele Ciampi; Roberta Casalini; Teresa Ramone; Rossella Elisei; Cristina Romei

doi:10.1530/endoabs.101.PS1-04-06

PS1-04-06

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Endocrine Abstracts (2024) 101 PS1-04-06 | DOI: 10.1530/endoabs.101.PS1-04-06

ETA2024 Poster Presentations Medullary thyroid cancer-1 (10 abstracts)

C-Cells hyperplasia, what is their role in the development of sporadic medullary cancer?

Jacqueline Almeida ¹ , Virginia Cappagli ² , Valeria Bottici ³ , Clara Ugolini ⁴ , francesca signorini ⁵ , Raffaele Ciampi ⁶ , Roberta Casalini ⁷ , Teresa Ramone ² , Rossella Elisei ⁸ & Cristina Romei ⁹

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¹University of Pisa, Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Pisa, Italy; ²Unità di Endocrinologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italia, Italy; ³University of Pisa, Department of Clinical and Experimental Medicine, Endocrine Unit, Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Pisa, Italy, Pisa, Italy; ⁴Università di Pisa, Dipartimento di Patologia Chirurgica, Medica, Molecolare e Dell’area Critica, Pisa, Italy; ⁵Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy, Dipartimento di Patologia Chirurgica, Medica, Molecolare e Dell’area Critica, Pisa, Italy; ⁶Uo Endocrinologia - Ospedale di CISA, Dipartimento di Medicina Clinica e S, Pisa, Italy; ⁷, University of Pisa, Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, Department of Clinical and Experimental Medicine, Pisa, Italy; ⁸University of Pisa, Endocrinology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy; ⁹Direzione Area di Medicina, University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy

Objectives: The aim of the present work was to verify if C-Cell hyperplasia (CCH) could be considered as a preneoplastic lesion of sporadic MTC and if CCH shares the same mutation profile of the main tumor

Methods: Forty-seven out of our whole series of 326 sMTC cases (14.4%) whose mutation profile was previously characterized by NGS were found to have CCH at histology. CCH formalin-fixed paraffin-embedded (FFPE) tissues were available in 20/47 selected cases. CCH area, identified by two independent pathologists, was micro dissected for DNA extraction: 15 cases were suitable for DNA analysis and 5 cases did not likely due to the very small area. CCH samples whose primary tumor was positive for a driver mutation were analyzed to track the same mutation by Sanger Sequencing and/or digital droplet PCR (ddPCR). In CCH samples whose primary tumor was negative, only RET Met918Thr was tracked.

Results: Eleven out of our selected 15 sMTC were found to be positive for the presence of a somatic mutation in the primary tumor: RET Cys634Arg n = 1; RET Met918Thr n = 3; RET Ser891Ala n = 2; HRAS Gln61Arg n = 1; HRAS Gly12Arg n = 1; KRAS Gly12Arg n = 2; KRAS Ala146Thr n = 1; four cases did not present any mutation. All but one CCH samples were negative for the mutations tracked. A HRAS Gln61Arg was found in a CCH samples (allelic frequency 0.4%) whose primary tumor was positive for the same mutation (allelic frequency 21.98%).This CCH positive case was ipsilateral of the main tumor and had a 30% of hyperplastic c-cells. The corresponding normal tissue was not affected by the HRAS mutation.

Conclusion: The present study showed that in most cases (10/11, 91%) CCH samples do not share the somatic mutation of the primary tumor thus hypothesizing that CCH is not related to sMTC development, and it could not likely be considered as a neoplastic precursor. The finding of a CCH case harboring the same mutation of the primary tumor suggests that in few cases CCH could be better considered as an emerging secondary tumor focus.