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A Proposal for Modification of the PSOGI Classification According to the Ki-67 Proliferation Index in Pseudomyxoma Peritonei

  • Peritoneal Surface Malignancy
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Pseudomyxoma peritonei (PMP) is a rare malignancy, classified according to the Peritoneal Surface Oncology Group International (PSOGI) classification, whose response to treatment remains highly heterogeneous within the high-grade (HG) category. Molecular profiling of PMP cases might help to better categorize patients and predict treatment responses.

Methods

We studied the Ki-67 proliferation rate and P53 overexpression in tissue samples from our historical cohort of HG-PMP patients. We established as cut-off levels the third quartile of each marker to perform univariate and multivariate Cox regression survival analyses. According to these results, the HG-PMP category was divided into subcategories and a new survival analysis was performed.

Results

A total of 90/117 patients with PMP undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were selected for secondary analysis. The survival analysis of the HG-PMP category for preoperative variables showed that a proliferation index defined by Ki-67 >15% is a bad prognostic factor, with a hazard ratio (HR) of 3.20 (95% confidence interval [CI] 1.24–8.25). Accordingly, the HG-PMP group was divided using the Ki-67 15% cut-off. The new PSOGI/Ki-67 variable was an independent prognostic factor for overall survival (OS), with an HR of 3.74 (95% CI 1.88–7.47), and disease-free survival (DFS), with an HR of 4.184 (95% CI 1.79–9.75). The estimated 5-year OS rate was 100%, 70% and 24% for the LG-PMP, HG-PMP ≤15% and HG-PMP >15% groups, respectively (p = 0.0001), while the 5-year DFS rate was 90%, 44% and 0%, respectively (p = 0.0001).

Conclusion

Division of the HG-PMP category of the PSOGI classification, according to the Ki-67 proliferation index, provides two well-defined subcategories, with significant differences in terms of OS and DFS, and hence high prognostic value.

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References

  1. Mittal R, Chandramohan A, Moran B. Pseudomyxoma peritonei: natural history and treatment. Int J Hyperthermia. 2017;33:511–9.

    Article  Google Scholar 

  2. Govaerts K, Lurvink RJ, De Hingh IHJT, et al. Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN clinical practice guidelines for diagnosis and treatment. Eur J Surg Oncol. 2021;47(1):S11-35.

    Article  Google Scholar 

  3. Carr NJ, Cecil TD, Mohamed F, et al. A consensus for classification and pathologic reporting of pseudomyxoma peritonei and associated appendiceal neoplasia: the results of the peritoneal surface oncology group international (PSOGI) modified delphi process. Am J Surg Pathol. 2016;40:14–26.

    Article  Google Scholar 

  4. Rufian-Andujar B, Valenzuela-Molina F, Rufian-Peña S, et al. From the Ronnett to the PSOGI classification system for pseudomyxoma peritonei: a validation study. Ann Surg Oncol. 2021;28:2819–27.

    Article  Google Scholar 

  5. Lund-Andersen C, Torgunrud A, Fleten KG, Flatmark K. Omics analyses in peritoneal metastasis—utility in the management of peritoneal metastases from colorectal cancer and pseudomyxoma peritonei: a narrative review. J Gastrointest Oncol. 2021;12(Suppl 1):S191–203.

    Article  Google Scholar 

  6. Shetty S, Thomas P, Ramanan B, et al. Kras mutations and p53 overexpression in pseudomyxoma peritonei: association with phenotype and prognosis. J Surg Res. 2013;180:97–103.

    Article  CAS  Google Scholar 

  7. Pietrantonio F, Perrone F, Mennitto A, et al. Toward the molecular dissection of peritoneal pseudomyxoma. Ann Oncol. 2016;27:2097–103.

    Article  CAS  Google Scholar 

  8. Yan F, Lin Y, Zhou Q, et al. Pathological prognostic factors of pseudomyxoma peritonei: comprehensive clinicopathological analysis of 155 cases. Hum Pathol. 2020;97:9–18.

    Article  CAS  Google Scholar 

  9. Menona SS, Guruvayoorappan C, Sakthivelc KM, Rasmi RR. Ki-67 protein as a tumour proliferation marker. Clin Chim Acta. 2019;491:39–45.

    Article  Google Scholar 

  10. Shigeki K, Torres Mesa PA, Cabras A, et al. The role of Ki-67 and pre-cytoreduction parameters in selecting diffuse malignant peritoneal mesothelioma (DMPM) patients for cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Ann Surg Oncol. 2015;23(5):1468–73.

    Google Scholar 

  11. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  Google Scholar 

  12. Delhorme JB, Severac F, Averous G, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei of appendicular and extra-appendicular origin. Br J Surg. 2018;105:668–76.

    Article  Google Scholar 

  13. Kusamura S, Barretta F, Yonemura Y, et al. The Role of Hyperthermic Intraperitoneal Chemotherapy in Pseudomyxoma Peritonei After Cytoreductive Surgery. JAMA Surg. 2021. https://doi.org/10.1001/jamasurg.2020.6363.

    Article  PubMed  Google Scholar 

  14. Li S, Balmain A, Counter CM. A model for RAS mutation patterns in cancers: finding the sweet spot. Nat Rev Cancer. 2018;18:767–77.

    Article  CAS  Google Scholar 

  15. Linardou H, Issa JD, Kanaloupiti D, et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008;9:962–72.

    Article  CAS  Google Scholar 

  16. Schneider MA, Eden J, Pache B, et al. Mutations of RAS/RAF proto-oncogenes impair survival after cytoreductive surgery and HIPEC for peritoneal metastasis of colorectal origin. Ann Surg. 2018;268:845–53.

    Article  Google Scholar 

  17. Arjona-Sanchez A, Rodriguez-Ortiz L, Baratti D, et al. RAS mutation decreases overall survival after optimal cytoreductive surgery and hyperthermic intraperitoneal chemotherapy of colorectal peritoneal metastasis: a modification proposal of the peritoneal surface disease severity score. Ann Surg Oncol. 2019;26:2595–604.

    Article  CAS  Google Scholar 

  18. Stein A, Strong E, Clark Gamblin T, et al. Molecular and genetic markers in appendiceal mucinous tumors: a systematic review. Ann Surg Oncol. 2020;27:85–97.

    Article  Google Scholar 

  19. Misdraji J, Burgart LJ, Lauwers GY. Defective mismatch repair in the pathogenesis of low-grade appendiceal mucinous neoplasms and adenocarcinomas. Mod Pathol. 2004;17:1447–54.

    Article  Google Scholar 

  20. Kabbani W, Houlihan P, Luthra R, et al. Mucinous and nonmucinous appendiceal adenocarcinomas: different clinicopathological features but similar genetic alterations. Mod Pathol. 2002;15:599–605.

    Article  Google Scholar 

  21. Noguchi R, Yano H, Gohda Y, et al. Molecular profiles of high-grade and low-grade pseudomyxoma peritonei. Cancer Med. 2015;4:1809–16.

    Article  CAS  Google Scholar 

  22. Bosman FT, Cameiro F, Hruban R. WHO classification of tumours: digestive system tumours 2019. Lyon Int Agency Res Cancer. 2019. https://doi.org/10.1111/his.13975.

    Article  Google Scholar 

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Funding

This work was supported by research project number PI19/01603 integrated into the Plan Estatal de I+D+I 2017-2020 and co-financed by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación and the Fondo Europeo de Desarrollo Regional (FEDER).

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Author notes

  1. Álvaro Arjona-Sánchez and Ana Martínez-López have contributed equally.

Authors and Affiliations

  1. Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Córdoba, Spain

    Álvaro Arjona-Sánchez PhD, Francisca Valenzuela-Molina MD, Blanca Rufián-Andújar MD, Sebastián Rufián-Peña PhD, Ángela Casado-Adam PhD, Juan Manuel Sánchez-Hidalgo PhD, Lidia Rodríguez-Ortiz MD, Francisco Javier Medina-Fernández PhD, Cesar Díaz-López PhD, Javier Briceño-Delgado PhD & Antonio Romero-Ruíz PhD

  2. GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, ReinaCórdoba, Spain

    Álvaro Arjona-Sánchez PhD, Ana Martínez-López MD, Francisca Valenzuela-Molina MD, Blanca Rufián-Andújar MD, Sebastián Rufián-Peña PhD, Ángela Casado-Adam PhD, Juan Manuel Sánchez-Hidalgo PhD, Lidia Rodríguez-Ortiz MD, Francisco Javier Medina-Fernández PhD, Cesar Díaz-López PhD, Melissa Granados-Rodríguez MD, Rosa Ortega-Salas PhD & Antonio Romero-Ruíz PhD

  3. Pathology Unit, Reina Sofia University Hospital, Córdoba, Spain

    Ana Martínez-López MD & Rosa Ortega-Salas PhD

  4. CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain

    Justo P. Castaño PhD

  5. CIBER Pathophysiology of Obesity and Nutrition, Carlos III Health Institute. Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain

    Manuel Tena-Sempere PhD

Authors
  1. Álvaro Arjona-Sánchez PhD
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  2. Ana Martínez-López MD
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Corresponding author

Correspondence to Álvaro Arjona-Sánchez PhD.

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Disclosures

Álvaro Arjona-Sánchez, Ana Martínez-López, Francisca Valenzuela-Molina, Blanca Rufián-Andújar, Sebastián Rufián-Peña, Ángela Casado-Adam, Juan Manuel Sánchez-Hidalgo, Lidia Rodríguez-Ortiz, Francisco Javier Medina-Fernández, Cesar Díaz-López, Melissa Granados-Rodríguez, Rosa Ortega-Salas, Justo P. Castaño, Manuel Tena-Sempere, Javier Briceño-Delgado, and Antonio Romero-Ruíz have no conflicts of interest to declare.

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Arjona-Sánchez, Á., Martínez-López, A., Valenzuela-Molina, F. et al. A Proposal for Modification of the PSOGI Classification According to the Ki-67 Proliferation Index in Pseudomyxoma Peritonei. Ann Surg Oncol 29, 126–136 (2022). https://doi.org/10.1245/s10434-021-10372-9

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