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The tissue expression pattern of CA 19.9 is associated with oncological features in medullary thyroid carcinoma

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Abstract

Purpose

Elevated serum levels of carbohydrate antigen 19.9 (CA19.9), a well-established tumor marker in pancreatic neoplasms, has been proposed as a prognostic marker of tumor aggressiveness in medullary thyroid carcinoma (MTC). A hypothesis of C-cell dedifferentiation has been raised. Here, we evaluated the expression of CA19.9 and CD133, a stem cell marker, in MTC tissues.

Methods

MTC samples from patients attending a university-based hospital were evaluated for CA19.9 and CD133 expression by immunohistochemistry. Clinical data were retrieved from medical records.

Results

Tumor specimens from 70 MTC patients (57.1% hereditary) were evaluated. The age at diagnosis was 36.1 ± 16.3 years, and 58.6% were female; 53% of patients had cervical and 20% distant metastases. CA19.9 staining was detected in 87% of the samples, but no association was observed with biochemical markers, tumor size, local or distant metastases (All P > 0.05). Remarkable, CA19.9 expression was higher in the metastasis than in primary tumor samples (P = 0.0002). CD133 was expressed in 90.5% samples, but no correlation was found with CA19.9. Interestingly, we identified three distinct expression patterns to CA19.9: individual, focal, and diffuse cells. Sporadic MTC was associated with the individual cell pattern (70.6%), while the hereditary form with the focal expression pattern (63.9%; P = 0.04). Remarkably, the diffuse pattern was associated with larger tumor size and distant metastases (P = 0.032).

Conclusions

The majority of samples stained for CA19.9, suggesting it is an MTC cell-intrinsic feature. Three distinct expression patterns were identified, which were associated with the hereditary or sporadic form, larger tumor size, and presence of metastases.

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Funding

This work has been made possible by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundo de Incentivo a Pesquisa (FIPE), and Programa de Apoio a Núcleos de Excelência (PRONEX)/Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

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Authors and Affiliations

  1. Thyroid Unit, Hospital de Clínicas de Porto Alegre, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Carla Vaz Ferreira Vargas, Lucieli Ceolin, Rafael Selbach Scheffel, Antônio Felippe Benini, Márcia Silveira Graudenz & Ana Luiza Maia

  2. Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Rafael Selbach Scheffel

  3. Pathology Division, Hospital de Clínicas de Porto Alegre, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Márcia Silveira Graudenz

Authors
  1. Carla Vaz Ferreira Vargas
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  2. Lucieli Ceolin
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Contributions

Conception and design: C.V.F.V., A.L.M. Provision of study materials or patients: A.L.M. Collection and assembly of data: all authors. Data analysis and interpretation: C.V.F.V., L.C., R.S.S., A.L.M. Manuscript writing: C.V.F., L.C., R.S.S., and A.L.M. Final approval of manuscript: all authors.

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Correspondence to Ana Luiza Maia.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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All patients or their legal guardians provided written informed consent by following the institutional Ethics Committee (CAAE 62017016300005327).

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Vargas, C.V.F., Ceolin, L., Scheffel, R.S. et al. The tissue expression pattern of CA 19.9 is associated with oncological features in medullary thyroid carcinoma. Endocrine 70, 544–551 (2020). https://doi.org/10.1007/s12020-020-02377-3

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