p53 Alteration and chromosomal instability in prostatic high-grade intraepithelial neoplasia and concurrent carcinoma: analysis by immunohistochemistry, interphase in situ hybridization, and sequencing of laser-captured microdissected specimens.

Abstract

p53 mutation has been shown to be associated with chromosomal instability (CI) in many human dysplastic and neoplastic lesions. However, the precise role of p53 in the pathogenesis of prostate carcinoma (Pca) is unknown. Topographic analysis of p53 alteration using immunohistochemistry (IHC) was performed on 35 archived prostatectomy specimens containing Pca foci; high-grade prostate intraepithelial neoplasia (HPIN) foci intermingled with cancer (HPINI) and situated away (HPINA). Specimens from 2 patients were topographically genotyped using laser capture microdissection, PCR amplification, and direct sequencing of p53 exons 5-9. CI was evaluated in the same tissue foci by interphase in situ hybridization (IFISH) using centromere probes for chromosomes 7, 8, and Y. p53 immunoreactivity was found in 20%, 17%, 0, and 0 in Pca, HPINI, HPINA, and benign epithelium, respectively. p53 molecular analysis in the specimens examined confirmed the IHC findings. IFISH revealed numerical chromosomal alterations in keeping with CI in 71% and 25% of p53+ and p53- Pca, respectively (P =.1), 67% and 0 of p53+ and p53- HPIN, respectively (P <.02), and in 27% and 0 of HPINI and HPINA, respectively. We concluded that p53 mutation is an early change in at least a subset of Pca. HPINI foci tend to have higher overall p53 immunoreactivity and CI than HPINA. The presence of p53 mutation in HPIN was associated with the presence of CI as determined by IFISH. Our study also provided additional evidence in support of the concept that HPIN might be the earliest precursor of cancer. Furthermore, our studies identify genomic similarities in HPINI and Pca, implying that carcinoma may arise from progression of certain HPIN foci that most likely harbor p53 mutation and/or more CI.

• Authors: J Al-Maghrabi, L Vorobyova, W Chapman, M Jewett, M Zielenska, J A Squire
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 14 Issue 12 Pg. 1252-62 (Dec 2001) ISSN: 0893-3952 [Print] United States
• PMID: 11743048 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• DNA, Neoplasm
• Tumor Suppressor Protein p53

Topics

• Aneuploidy
• Carcinoma (chemistry, genetics, pathology)
• DNA, Neoplasm (analysis)
• Dissection (methods)
• Genes, p53
• Humans
• Immunoenzyme Techniques
• In Situ Hybridization, Fluorescence
• Interphase
• Lasers
• Male
• Mutation
• Polymerase Chain Reaction
• Prostatic Intraepithelial Neoplasia (chemistry, genetics, pathology)
• Prostatic Neoplasms (chemistry, genetics, pathology)
• Sequence Analysis, DNA
• Tumor Suppressor Protein p53 (analysis)