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Virchows Archiv

, Volume 470, Issue 6, pp 695–701 | Cite as

Strong association of insulin-like growth factor 1 receptor expression with histologic grade, subtype, and HPV status in penile squamous cell carcinomas: a tissue microarray study of 112 cases

  • Sheila F. Faraj
  • Nilda Gonzalez-Roibon
  • Enrico Munari
  • Rajni Sharma
  • Arthur L. Burnett
  • Antonio L. Cubilla
  • George J. Netto
  • Alcides Chaux
Original Article

Abstract

Insulin-like growth factor-1 receptor (IGF1R) plays a key role in cell growth and transformation. It is overexpressed in several solid tumors. This study evaluates IGF1R immunoexpression in penile squamous cell carcinoma (SCC). Four tissue microarrays were built from formalin-fixed, paraffin-embedded blocks of 112 penile SCC from Paraguay. Membranous IGF1R expression was evaluated by immunohistochemistry using two different approaches. An H-score was calculated in each spot (stain intensity by extent), and a median score per tumor was obtained. The second approach consisted of a score similar to the scoring system that was used for evaluating HER2 immunoexpression. For each case, the highest category obtained at any spot was used for statistical analyses. IGF1R expression was compared by histologic subtype, grade, and human papillomavirus (HPV) status. Median H-score was 22.5. The distribution of IGF1R expression by HER2 approach was as follows: 0 in 33.0% cases, 1+ in 46.4%, 2+ in 14.3%, and 3+ in 6.2%. IGF1R H-scores were associated with basaloid and warty/basaloid subtypes (p = 0.0026) and higher grade (p = 0.00052). Although weaker when using the HER2 approach, the association of IGF1R expression with subtype (p = 0.015) and grade (p = 0.015) remained significant. Furthermore, there was an association between IGF1R expression by HER2 approach and HPV status (p = 0.012). IGF1R was expressed in about two thirds of penile SCC cases, showing a strong positive association with histologic grade, subtype, and HPV status. Considering that grade is a predictor of outcome IGF1R expression may have prognostic relevance and could point to a potential role for IGF1R inhibitors in treating penile SCC.

Keywords

IGF1R Penile carcinoma Squamous cell carcinoma 

Notes

Acknowledgements

We acknowledge the outstanding work of Helen Fedor and Marcella Southerland, from the TMA Lab Core at the Johns Hopkins University, in building the TMAs for the study.

Compliance with ethical standards

Support/financial disclosure

This study was partially supported by the Johns Hopkins Medicine—Patana Fund for Research. Dr. Alcides Chaux was partially supported by an award granted by the National Council of Science and Technology (CONACYT) dependent of the Presidency of the Republic of Paraguay, as an Active Researcher of Level 2 of the National Incentive Program for Researchers (PRONII).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2017_2110_Fig3_ESM.gif (74 kb)
Supplementary Figure 1

Histologic subtypes, grades, HPV status and IGF1R expression distribution. Bar plots showing distribution of A) histologic subtypes, B) histologic grades, C) HPV status, D) IGF1R expression by H-scores using histograms, and E) by HER2 approach using bar plots. (GIF 74 kb)

428_2017_2110_MOESM1_ESM.tif (43.2 mb)
High resolution images (TIFF 44245 kb)
428_2017_2110_Fig4_ESM.gif (84 kb)
Supplementary Figure 2

Association of A) histologic subtypes, B) histologic grades, and C) HPV status with IGF1R expression by H-score. Association of D) histologic subtypes, E) histologic grades, and F) HPV status with IGF1R expression by H-score, using base 10 logarithmic scale. (GIF 83 kb)

428_2017_2110_MOESM2_ESM.tif (44.2 mb)
High resolution images (TIFF 45283 kb)
428_2017_2110_Fig5_ESM.gif (49 kb)
Supplementary Figure 3

Association of A) histologic subtypes, B) histologic grades, and C) HPV status with IGF1R expression by HER2 approach. (GIF 49 kb)

428_2017_2110_MOESM3_ESM.tif (21.9 mb)
High resolution images (TIFF 22375 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Sheila F. Faraj
    • 1
  • Nilda Gonzalez-Roibon
    • 1
  • Enrico Munari
    • 1
  • Rajni Sharma
    • 1
  • Arthur L. Burnett
    • 2
  • Antonio L. Cubilla
    • 3
  • George J. Netto
    • 4
    • 5
  • Alcides Chaux
    • 6
  1. 1.Department of PathologyJohns Hopkins Medical InstitutionsBaltimoreUSA
  2. 2.Department of UrologyJohns Hopkins Medical InstitutionsBaltimoreUSA
  3. 3.Instituto de Patología e InvestigaciónAsunciónParaguay
  4. 4.Johns Hopkins Medical InstitutionsBaltimoreUSA
  5. 5.Department of PathologyThe University of Alabama at BirminghamBirminghamUSA
  6. 6.Centro para el Desarrollo de la Investigación Científica (CEDIC)AsunciónParaguay

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