title: 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.
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.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Sheila F
authors.initials: SF
authors.lastname: Faraj
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Nilda
authors.initials: N
authors.lastname: Gonzalez-Roibon
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Burnett
authors.affiliation: Instituto de Patología e Investigación, Asunción, Paraguay.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Cubilla
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, MD, USA. gnetto@uabmc.edu.|Department of Pathology, The University of Alabama at Birmingham, WP Building, Suite P230 l 619 19th Street, South, Birmingham, AL, 35249-7331, USA. gnetto@uabmc.edu.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: Centro para el Desarrollo de la Investigación Científica (CEDIC), Asunción, Paraguay.
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D030361:Papillomavirus Infections / Q000150:complications; D010412:Penile Neoplasms / Q000473:pathology* / Q000821:virology; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1
keywords: IGF1R; Penile carcinoma; Squamous cell carcinoma