Strong Association of Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Histologic Grade in Penile Squamous Cell Carcinomas
Alcides Chaux, Enrico Munari, Sheila F Faraj, Nilda Gonzalez-Roibon, Rajni Sharma, Antonio L Cubilla, George J Netto. Johns Hopkins Hospital, Baltimore, MD; Norte University, Asuncion, Paraguay; Instituto de Patologia e Investigacion, Asuncion, Paraguay
Background: The insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase receptor that plays a key role in cell growth and transformation. IGF1R is overexpressed in several solid tumors. Trials of IGFR1 inhibitors are underway. IGF1R expression status has not been determined in invasive penile squamous cell carcinomas (SCC). This study evaluates IGF1R immunoexpression in SCC.
Design: Tissue microarrays (TMA) were constructed from FFPE tissues of 112 penile SCC from Paraguay. Each tumor was sampled 3–12 times. Histologic subtyping and grading was done using recently published criteria (Hum Pathol 2012;43:771). Membranous IGF1R expression was evaluated by immunohistochemistry (G11, Ventana Medical Systems). H score was calculated in each spot [Σ (stain intensity X extent)] and a median score per tumor was obtained. Proportions were compared using the Fisher's exact test. H Scores were compared using the Kruskal-Wallis test. Logistic regression was used for multivariate analyses.
Results: Distribution of subtypes was as follows: usual SCC, 48 cases; warty-basaloid carcinoma, 25 cases; warty carcinoma, 16 cases; basaloid carcinoma, 11 cases; papillary carcinoma, 9 cases; and 1 case each of sarcomatoid, verrucous, and usual-verrucous (hybrid) carcinomas. Distribution of histologic grades vas as follows: grade 1, 5 cases; grade 2, 30 cases; grade 3, 77 cases. Human papillomavirus (HPV) DNA was detected by PCR in 20 of 52 (38%) analyzed samples. IGF1R expression was not associated with HPV status (P=0.13) or histologic subtype (P=0.07). Using >10% extent expression as a cut-off for IGF1R overexpression, 64 cases (57%) demonstrated IGF1R overexpression. Overexpression was strongly associated with histologic grade: 11/35 (31%) of low-grade (grades 1 and 2) Vs 53/77 (69%) of high-grade (grade 3) penile SCC (P<0.001). The association between IGF1R overexpression and high grade remained strong (P=0.001) when adjusting for histologic subtype.
Conclusions: IGF1R is overexpressed in 57% of penile SCC showing a strong association with high grade regardless of histologic subtype. Our results suggest that immunohistochemical expression level of IGF1R may have prognostic relevance and could point to a potential role for IGF1R inhibitors in treating penile SCC.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 212, Tuesday Afternoon