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ΔNp73 status in peritoneal and ovarian dissemination of appendicular adenocarcinoids (goblet cells)

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Abstract

Introduction

Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3–0.9% of the appendectomies, 35–58% of all appendicular neoplasms, and less than 14% of malign appendix tumors. The most frequent clinical presentation is abdominal pain associated with a picture of acute appendicitis.

Materials and methods

We present 3 clinical cases of appendix GCC, 2 subjected to cytoreductory surgery plus intraperitoneal hyperthermic chemotherapy and a third, who is currently receiving neoadjuvant treatment with a good response to chemotherapy and who will be offered the same treatment as the first two patients. Given the unpredictable behavior of these tumors, the use of molecular markers could help us to predict their behavior and prognosis. In this context, the TP73 gene would make an interesting putative marker. ∆Np73 has been described as overexpressed in a great variety of tumor types including colon cancer and this up-regulation is associated with a poor prognosis. To evidence its role in this malignancy, we evaluate here the status of ∆Np73 in the primary tumor and normal counterpart tissues, in the metastatic implants and in healthy areas of the peritoneum from the appendicular GCC patients. In addition, we checked the expression levels of this p73 variant in the tumor and normal tissue of 26 patients with colon cancer.

Results

Remarkably, 2 patients showed significant ∆Np73 down-regulation in both the primary tumor and the implants. Case 1 presented a fourfold decrease of levels in the primary tumor and 20-fold decrease in the implants. Case 2 showed a seven- and fourfold down-regulation in the primary tumor and implants, respectively. However, Case 3 showed an up-regulation of 53- and threefold in the primary tumor and implants, respectively.

Conclusion

Goblet cell carcinoma of the appendix is very rate. It tends to seed throughout the peritoneum, making aggressive surgical cytoreduction and chemotherapy viable treatment options. Investigation into the molecular basis of these tumors may improve the diagnosis, prognosis and therapeutic decisions regarding these patients. ∆Np73 seems a good candidate for further analysis in longer series.

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Acknowledgements

We acknowledge ISCIII, FIS, FEDER and Cátedra UAM-ROCHE de Medicina de Innovación for funding our current research through the PI18/00473 and CIBERONIC. Gemma Domínguez and Nuria Rodriguez have received research grants from Roche Farma SA.

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Authors and Affiliations

  1. Peritoneal Oncological Surgery Unit, Hospital La Paz, Madrid, Spain

    M. I. Prieto-Nieto, D. Pastor & J. P. Pérez

  2. Department of Medicine, Faculty of Medicine, Institute of Biomedical Research Alberto Sols, CSIC-UAM, Madrid, Spain

    J. Rodríguez-Cobos, J. Santos-López, M. Cano-Vega & G. Domínguez

  3. Pathological Department, Hospital La Paz, Madrid, Spain

    C. Méndez & E. Palacios

  4. Biobanco Idipaz, Hospital Universitario La Paz, Idipaz, Madrid, Spain

    M. Arranz-Alvarez

  5. Medical Oncology Department, Hospital La Paz, Madrid, Spain

    D. Viñal & N. Rodríguez

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  1. M. I. Prieto-Nieto
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  2. D. Pastor
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  3. J. Rodríguez-Cobos
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  4. J. P. Pérez
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  5. C. Méndez
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  9. M. Cano-Vega
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  10. D. Viñal
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  11. N. Rodríguez
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Corresponding authors

Correspondence to M. I. Prieto-Nieto or G. Domínguez.

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Conflict of interest

Nuria Rodríguez and Gemma Domínguez are funded by Roche Farma through “Cátedra de Medicina de Innovación UAM-ROCHE”, for conducting teaching and research programs in the context of the Universidad Autónoma de Madrid. The other authors declare no conflict of interest.

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

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Prieto-Nieto, M.I., Pastor, D., Rodríguez-Cobos, J. et al. ΔNp73 status in peritoneal and ovarian dissemination of appendicular adenocarcinoids (goblet cells). Clin Transl Oncol 21, 1432–1439 (2019). https://doi.org/10.1007/s12094-019-02091-1

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