title: D2-40 immunoreactivity in penile squamous cell carcinoma: a marker of aggressiveness.
abstract: D2-40 immunohistochemical expression was investigated in tissue specimens from 39 patients with squamous cell carcinoma of the penis who underwent partial or total penectomy between 1987 and 2008. Patient age, tumor size, and grade; D2-40-positive lymphatic vessel density in intratumoral, peritumoral, and normal tissue; cell positivity for D2-40 in intratumoral and normal tissue; and D2-40 staining intensity and distribution were analyzed and correlated with disease-specific survival. Analysis of D2-40-positive lymphatics disclosed that mean lymphatic vessel density was greater in peritumoral tissue than in intratumoral and normal tissue and lower in patients with lymph node metastasis than in those without lymph node metastasis. The receiver operating characteristic curve showed that an intratumoral lymphatic vessel density greater than 2.0 had 83.3% sensitivity and 78% specificity in predicting lymph node metastasis. Analysis of cell immunoreactivity showed cytoplasmic D2-40 positivity in intratumoral and normal tissue in 89.7% and 65.5% of patients, respectively. A strong correlation emerged between grade of cell differentiation and D2-40 immunoreactivity in intratumoral tissue; in particular, 88.9% of tumors with weak podoplanin expression were G1, whereas strong cellular immunoreactivity was detected in 83.3% of G3 patients (P = .003; χ(2) test). A significant correlation was also noted between pattern of reactivity and tumor grade because the basal layer was positive in patients with undifferentiated tumors (100% of G3) and in 72.2% of G1 tumors (P = .021; χ(2) test). D2-40 seems to be a useful marker for the development of node metastasis in squamous cell carcinoma of the penis, although validation in larger series is required to confirm its predictive value.
authors.affiliation: Department of Clinical and Specialist Sciences-Urology, Polytechnic University of Marche Medical School-United Hospitals, 60020 Ancona, Italy. d.minardi@univpm.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Minardi
authors.forename: Gianluca
authors.initials: G
authors.lastname: d'Anzeo
authors.forename: Guendalina
authors.initials: G
authors.lastname: Lucarini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Filosa
authors.forename: Antonio
authors.initials: A
authors.lastname: Zizzi
authors.forename: Oriana
authors.initials: O
authors.lastname: Simonetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Polito
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Offidani
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Primio
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Muzzonigro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D010412:Penile Neoplasms / Q000473:pathology; D011237:Predictive Value of Tests; D016019:Survival Analysis
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C500987:monoclonal antibody D2-40