Immunohistochemical expression of the mammalian target of rapamycin pathway in penile squamous cell carcinomas

A tissue microarray study of 112 cases

Alcides Chaux, Enrico Munari, Antonio L. Cubilla, Jessica Hicks, Kristen Lecksell, Arthur Burnett, George J. Netto

Research output: Contribution to journalArticle

Abstract

Aims: The aim of this study was to evaluate the immunohistochemical expression of mammalian target of rapamycin (mTOR) pathway-related biomarkers in penile carcinomas, and to assess associations with histological type, histological grade, and human papillomavirus (HPV) infection. Methods and results: We built four tissue microarrays from 112 invasive penile squamous cell carcinomas, and evaluated the immunohistochemical expression of PTEN, phospho-AKT, phospho-mTOR, and phospho-S6. We found decreased or loss of PTEN expression in 87% of cases. Warty and/or basaloid carcinomas had a higher proportion of PTEN loss (P = 0.02), whereas keratinizing tumours showed higher levels of phospho-S6 (P = 0.009); phospho-AKT and phospho-mTOR levels were not significantly different between warty/basaloid and keratinizing carcinomas (P = 0.75 and P = 0.77, respectively). PTEN was not associated with histological grade (P = 0.18). Expression levels of phospho-S6 were significantly higher in low-grade tumours (P = 0.001), whereas expression levels of phospho-AKT and phospho-mTOR were slightly higher in high-grade tumours (P = 0.01 and P = 0.35, respectively). We did not find any association between HPV infection and mTOR markers (P ≥ 0.2 in all cases). Conclusions: Our results provide evidence of dysregulation of the mTOR pathway in penile carcinomas independently of HPV infection. Future clinical studies should further evaluate the prognostic and predictive usefulness of these markers in patients with penile cancer.

Original languageEnglish (US)
Pages (from-to)863-871
Number of pages9
JournalHistopathology
Volume64
Issue number6
DOIs
StatePublished - 2014

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Sirolimus
Squamous Cell Carcinoma
S 6
Papillomavirus Infections
Carcinoma
Penile Neoplasms
Neoplasms
Biomarkers

Keywords

  • Human papillomavirus
  • Mammalian target of rapamycin
  • mTOR
  • Penile cancer
  • PTEN
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Immunohistochemical expression of the mammalian target of rapamycin pathway in penile squamous cell carcinomas : A tissue microarray study of 112 cases. / Chaux, Alcides; Munari, Enrico; Cubilla, Antonio L.; Hicks, Jessica; Lecksell, Kristen; Burnett, Arthur; Netto, George J.

In: Histopathology, Vol. 64, No. 6, 2014, p. 863-871.

Research output: Contribution to journalArticle

Chaux, Alcides ; Munari, Enrico ; Cubilla, Antonio L. ; Hicks, Jessica ; Lecksell, Kristen ; Burnett, Arthur ; Netto, George J. / Immunohistochemical expression of the mammalian target of rapamycin pathway in penile squamous cell carcinomas : A tissue microarray study of 112 cases. In: Histopathology. 2014 ; Vol. 64, No. 6. pp. 863-871.
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AU - Hicks, Jessica

AU - Lecksell, Kristen

AU - Burnett, Arthur

AU - Netto, George J.

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N2 - Aims: The aim of this study was to evaluate the immunohistochemical expression of mammalian target of rapamycin (mTOR) pathway-related biomarkers in penile carcinomas, and to assess associations with histological type, histological grade, and human papillomavirus (HPV) infection. Methods and results: We built four tissue microarrays from 112 invasive penile squamous cell carcinomas, and evaluated the immunohistochemical expression of PTEN, phospho-AKT, phospho-mTOR, and phospho-S6. We found decreased or loss of PTEN expression in 87% of cases. Warty and/or basaloid carcinomas had a higher proportion of PTEN loss (P = 0.02), whereas keratinizing tumours showed higher levels of phospho-S6 (P = 0.009); phospho-AKT and phospho-mTOR levels were not significantly different between warty/basaloid and keratinizing carcinomas (P = 0.75 and P = 0.77, respectively). PTEN was not associated with histological grade (P = 0.18). Expression levels of phospho-S6 were significantly higher in low-grade tumours (P = 0.001), whereas expression levels of phospho-AKT and phospho-mTOR were slightly higher in high-grade tumours (P = 0.01 and P = 0.35, respectively). We did not find any association between HPV infection and mTOR markers (P ≥ 0.2 in all cases). Conclusions: Our results provide evidence of dysregulation of the mTOR pathway in penile carcinomas independently of HPV infection. Future clinical studies should further evaluate the prognostic and predictive usefulness of these markers in patients with penile cancer.

AB - Aims: The aim of this study was to evaluate the immunohistochemical expression of mammalian target of rapamycin (mTOR) pathway-related biomarkers in penile carcinomas, and to assess associations with histological type, histological grade, and human papillomavirus (HPV) infection. Methods and results: We built four tissue microarrays from 112 invasive penile squamous cell carcinomas, and evaluated the immunohistochemical expression of PTEN, phospho-AKT, phospho-mTOR, and phospho-S6. We found decreased or loss of PTEN expression in 87% of cases. Warty and/or basaloid carcinomas had a higher proportion of PTEN loss (P = 0.02), whereas keratinizing tumours showed higher levels of phospho-S6 (P = 0.009); phospho-AKT and phospho-mTOR levels were not significantly different between warty/basaloid and keratinizing carcinomas (P = 0.75 and P = 0.77, respectively). PTEN was not associated with histological grade (P = 0.18). Expression levels of phospho-S6 were significantly higher in low-grade tumours (P = 0.001), whereas expression levels of phospho-AKT and phospho-mTOR were slightly higher in high-grade tumours (P = 0.01 and P = 0.35, respectively). We did not find any association between HPV infection and mTOR markers (P ≥ 0.2 in all cases). Conclusions: Our results provide evidence of dysregulation of the mTOR pathway in penile carcinomas independently of HPV infection. Future clinical studies should further evaluate the prognostic and predictive usefulness of these markers in patients with penile cancer.

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