title: A clinical, pathologic, and molecular study of p53 and murine double minute 2 in penile carcinogenesis and its relation to prognosis.
abstract: Penile carcinoma constitutes up to 16% of male malignancies in developing countries. Changes in the p53 and murine double minute 2 pathway are important events in various cancers. Associate alterations in murine double minute 2 and p53 expression were evaluated by molecular techniques, with the clinical data of 297 cases of penile carcinoma. Automated immunohistochemistry was performed for murine double minute 2 and p53 using the primary antibodies SPM14 and DO7, respectively. Fluorescent in situ hybridization was performed using the probes murine double minute 2 at 12q15 and TP53 at 17p13.1. Slides were digitalized, and bright-field and fluorescent images were analyzed. TP53 was sequenced in 16 cases. The expression of p53 was higher in poorly differentiated, infiltrative border, corpus spongiosum, corpora cavernosa, and invasive urethral carcinomas. Patients who died of disease also expressed higher levels of p53. p53-negative tumors were associated with higher overall survival. Murine double minute 2 showed no difference of expression in any group of tumors, no correlation with p53 expression. No alterations in genes or chromosomes were observed. Mutations in TP53 were observed in 4 of 16 cases: p.T170M, p.L252P, p.C176Y, and the novel c.803_810del8; these changes correlated with p53 expression by immunohistochemistry. Murine double minute 2 is not useful in the prognosis of penile carcinoma by immunohistochemistry. Additional studies on the transcriptional, posttranscriptional, and epigenetic aspects are necessary to understand the interactions between p53 and murine double minute 2 because we did not observe any numeric alterations by fluorescent in situ hybridization. Examining p53 is helpful in identifying patients with more aggressive tumors and may be crucial in selecting the most suitable surgical procedure.
authors.affiliation: Department of Pathology, Hospital do Cancer A C Camargo - Fundação Antônio Prudente, São Paulo, Brazil. rafael.malagoli@gmail.com
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
authors.forename: Julianna Alves
authors.initials: JA
authors.lastname: Ignácio
authors.forename: José
authors.initials: J
authors.lastname: Jordán
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.forename: Bianca
authors.initials: B
authors.lastname: Lisboa
authors.forename: Ademar
authors.initials: A
authors.lastname: Lopes
authors.forename: Kátia Cândido
authors.initials: KC
authors.lastname: Carvalho
authors.forename: Isabela Werneck
authors.initials: IW
authors.lastname: da Cunha
authors.forename: Antônio
authors.initials: A
authors.lastname: Cubilla
authors.forename: Gustavo Cardoso
authors.initials: GC
authors.lastname: Guimarães
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
mesh_terms: D000906:Antibodies; D001938:Brazil / Q000453:epidemiology; D002277:Carcinoma / Q000401:mortality / Q000473:pathology*; D002869:Chromosome Aberrations; D016001:Confidence Intervals; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010412:Penile Neoplasms / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2