Intratumoral Heterogeneity of SMAD4 Immunohistochemical Expression and Its Role in Prediction of Recurrence Pattern in Patients with Resectable Pancreatic Cancer

  • Ilya PokataevEmail author
  • Asel Kudaibergenova
  • Anna Artemyeva
  • Anna Popova
  • Alexey Rumyantsev
  • Danil Podluzhny
  • Nikolay Kudashkin
  • Mikhail Fedyanin
  • Alexey Tryakin
  • Sergey Tjulandin
Original Research



The aim of our study was to evaluate consistency of SMAD4 expression in different tumor areas and its correlation with recurrence pattern in patients after resection for pancreatic cancer (PC).


Records of patients who underwent resection for nonmetastatic PC between 2001 and 2015 were analyzed. Formalin-fixed, paraffin-embedded tissue sections from different areas of primary tumor and lymph node metastases were analyzed immunohistochemically (IHC) for SMAD4 expression using TMA technology.


SMAD4 expression was assessed in 356 tissue sections obtained from 91 patients. SMAD4 expression was positive in all assessed tumor slides only in 7 of 26 patients (26.9%). There were 54 recurrences (9 locoregional, 41 distant, and 4 both local and distant) with median follow-up of 21.7 months. There was no correlation between SMAD4 expression and locoregional recurrence pattern (p = 0.30). SMAD4 status influenced neither distant recurrence-free survival (p = 0.99) nor overall survival (p = 0.13).


Different areas inside primary tumor and lymph node metastases express SMAD4 heterogeneously. SMAD4 IHC expression is not a biomarker of the recurrence pattern after surgical resection for PC.


Pancreatic neoplasms Smad4 protein Recurrence pattern 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Financial Support

The study was funded by N.N. Blokhin Russian Cancer Research Center. No other support was done.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ilya Pokataev
    • 1
    Email author
  • Asel Kudaibergenova
    • 2
  • Anna Artemyeva
    • 3
  • Anna Popova
    • 1
  • Alexey Rumyantsev
    • 1
  • Danil Podluzhny
    • 4
  • Nikolay Kudashkin
    • 4
  • Mikhail Fedyanin
    • 1
  • Alexey Tryakin
    • 1
  • Sergey Tjulandin
    • 1
  1. 1.Department of Clinical Pharmacology and ChemotherapyFederal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian FederationMoscowRussia
  2. 2.Department of CytologyFederal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian FederationMoscowRussia
  3. 3.Department of PathologyN.N. Petrov Cancer Research InstituteSaint PetersburgRussia
  4. 4.Department of Surgery #7Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian FederationMoscowRussia

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