Different patterns of p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: Analysis of microdissected specimens

Yutaka Yasunaga, Masaru Shin, Masaki Q. Fujita, Norio Nonomura, Tsuneharu Miki, Akihiko Okuyama, Katsuyuki Aozasa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Prostatic intraepithelial neoplasia (PIN) is characterized by intraluminal proliferation of epithelial cells and can be divided into high- grade (HGPIN) and low-grade (LGPIN) lesions. HGPiN is regarded as the most likely precursor of prostatic carcinoma (PCA). Microdissected DNA selectively extracted from paraffin-embedded sections of 29 cases of PCA and I benign prostatic hypertrophy were analyzed for p53 mutation by single-strand conformation polymorphism (SSCP) of polymerase chain reaction (PCR)-amplified DNA fragments followed by direct sequencing. These patients had received total prostatectomy (27 cases) or transurethral resection (3 cases). Under direct microscopic observation, DNA was microdissected from 108 lesions: 67 lesions from 22 cases of PIN (55 HGPIN and 12 LGPIN). 29 from 22 cases of PCA, and 12 from 11: cases of adjoining benign glands. Analysis revealed 13 mutations in 10 lesions from six cases. All 13 were point mutations: 7 missense, 5 silent, and 1 nonsense. Mutations were detected in 3 cases (14%) of PIN and 5 cases (25%) of PCA. PIN lesions with p53 mutations were all categorized as HGPIN. Neither LGPIN nor benign glands adjoining PIN and/or PCA had mutations. Two PIN and one PCA lesion in each of two cases had mutations that were different from each other. G-to-A transition was the commonest mutation pattern. The current findings showed that HGPIN, but not LGPIN, and PCA are similar with regard to p53 mutation. The diverse patterns of p53 mutation among HGPIN and PCA lesions suggested multiclonal development of prostatic precancerous lesions.

Original languageEnglish
Pages (from-to)1275-1279
Number of pages5
JournalLaboratory Investigation
Volume78
Issue number10
Publication statusPublished - 1998 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Different patterns of p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: Analysis of microdissected specimens'. Together they form a unique fingerprint.

  • Cite this