Medical Oncology

, 36:8 | Cite as

The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma

  • Alexandre A. B. A. da CostaEmail author
  • Felipe D’Almeida Costa
  • Daniel Vilarim Araújo
  • Marcos Pedro Guedes Camandaroba
  • Victor Hugo Fonseca de Jesus
  • Audrey Oliveira
  • Ana Caroline Fonseca Alves
  • Carlos Stecca
  • Larissa Machado
  • Andrea Cruz Feraz de Oliveira
  • Thiago Bueno de Oliveira
  • Ulisses Ribaldo Nicolau
  • Vladmir Cláudio Cordeiro de Lima
Original Paper


There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone (n = 37) or chemotherapy with cetuximab (n = 75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab + CT versus CT alone was 11.4 months and 7.0 months, (p = 0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months (p = 0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months (p = 0.002) and a mPFS of 3.2 months versus 4.7 months (p = 0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27–4.08; p = 0.006) and with PFS (HR 1.85; 95% CI 1.09–2.99; p = 0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab + CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response.


Cetuximab resistance Head and neck squamous cell carcinoma PTEN MET P16 Predictive factors Prognostic factors 



This work was supported by the Ricardo Brentani Award, A.C. Camargo Cancer Center.

Compliance with ethical standards

Conflict of interest

None to declare.

Ethical approval

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. For this type of study formal consent is not required.

Supplementary material

12032_2018_1234_MOESM1_ESM.jpg (423 kb)
Kaplan-Meier curves for overall survival according to ECOG performance status (A), smoking history (B), and type of recurrent disease (C). Progression-free survival according to age at diagnosis (D). Supplementary material 1 (JPG 423 KB)
12032_2018_1234_MOESM2_ESM.jpg (414 kb)
Kaplan-Meier curves for overall survival and progression-free survival according to CMET expression (A and C) and p16 expression (B and D) are presented, respectively in each case. Supplementary material 2 (JPG 413 KB)
12032_2018_1234_MOESM3_ESM.docx (63 kb)
Supplementary material 3 (DOCX 63 KB)
12032_2018_1234_MOESM4_ESM.docx (70 kb)
Supplementary material 4 (DOCX 70 KB)


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Copyright information

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

Authors and Affiliations

  • Alexandre A. B. A. da Costa
    • 1
    Email author
  • Felipe D’Almeida Costa
    • 2
  • Daniel Vilarim Araújo
    • 1
  • Marcos Pedro Guedes Camandaroba
    • 1
  • Victor Hugo Fonseca de Jesus
    • 1
  • Audrey Oliveira
    • 1
  • Ana Caroline Fonseca Alves
    • 1
  • Carlos Stecca
    • 1
  • Larissa Machado
    • 1
  • Andrea Cruz Feraz de Oliveira
    • 2
  • Thiago Bueno de Oliveira
    • 1
  • Ulisses Ribaldo Nicolau
    • 1
  • Vladmir Cláudio Cordeiro de Lima
    • 1
  1. 1.A.C. Camargo Cancer Center - Medical Oncology DepartmentSão PauloBrazil
  2. 2.A.C. Camargo Cancer Center – Pathology DepartmentSão PauloBrazil

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