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Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.

Koga F, Kawakami S, Kumagai J, Takizawa T, Ando N, Arai G, Kageyama Y, Kihara K - Br. J. Cancer (2003)

Bottom Line: At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues.Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms.Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.

ABSTRACT
p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a Delta N-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues. In cultured cells, Delta Np63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

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Representative photomicrographs of immunostaining for p63, ΔNp63, and β-catenin in urothelial tissues. (A–F) Immunostaining of p63 with the 4A4 antibody that recognises all isoforms of p63: (A) intense staining in normal urothelium (× 200), (B) intense staining in an LPN tumour (× 200), (C) gradual diminution of p63 expression towards the superficial cell layers in an LPN tumour (× 100), (D) weak staining in a high-grade muscle-invasive carcinoma (× 200), (E) loss of staining in a high-grade muscle-invasive carcinoma (× 200), and (F) weak staining in CIS (× 200). (G and H) Immunoreactivity with the 4A4 antibody (G) is virtually identical to that with the ΔNp63-specific antibody Ab-1 (H) (× 100). (I and J) Immunostaining of β-catenin: (I) normal β-catenin expression with homogeneously positive staining at the cell membrane preserved in an LPN tumour (× 200) and (J) reduced (heterogeneously positive) β-catenin expression in a muscle-invasive carcinoma (× 200).
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fig1: Representative photomicrographs of immunostaining for p63, ΔNp63, and β-catenin in urothelial tissues. (A–F) Immunostaining of p63 with the 4A4 antibody that recognises all isoforms of p63: (A) intense staining in normal urothelium (× 200), (B) intense staining in an LPN tumour (× 200), (C) gradual diminution of p63 expression towards the superficial cell layers in an LPN tumour (× 100), (D) weak staining in a high-grade muscle-invasive carcinoma (× 200), (E) loss of staining in a high-grade muscle-invasive carcinoma (× 200), and (F) weak staining in CIS (× 200). (G and H) Immunoreactivity with the 4A4 antibody (G) is virtually identical to that with the ΔNp63-specific antibody Ab-1 (H) (× 100). (I and J) Immunostaining of β-catenin: (I) normal β-catenin expression with homogeneously positive staining at the cell membrane preserved in an LPN tumour (× 200) and (J) reduced (heterogeneously positive) β-catenin expression in a muscle-invasive carcinoma (× 200).

Mentions: We initially evaluated p63 protein expression on normal urothelium and urothelial tumour tissues. Immunoreactivity for p63 was localised to nuclei of normal and neoplastic urothelial cells. Except the urothelium, normal tissues of the kidney, ureter, and urinary bladder were negative for p63. In normal urothelium, almost entire basal and intermediate cells (4–5 layers from the basement membrane) showed intense staining, but immunoreactivity was undetectable in umbrella cells (Figure 1AFigure 1


Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.

Koga F, Kawakami S, Kumagai J, Takizawa T, Ando N, Arai G, Kageyama Y, Kihara K - Br. J. Cancer (2003)

Representative photomicrographs of immunostaining for p63, ΔNp63, and β-catenin in urothelial tissues. (A–F) Immunostaining of p63 with the 4A4 antibody that recognises all isoforms of p63: (A) intense staining in normal urothelium (× 200), (B) intense staining in an LPN tumour (× 200), (C) gradual diminution of p63 expression towards the superficial cell layers in an LPN tumour (× 100), (D) weak staining in a high-grade muscle-invasive carcinoma (× 200), (E) loss of staining in a high-grade muscle-invasive carcinoma (× 200), and (F) weak staining in CIS (× 200). (G and H) Immunoreactivity with the 4A4 antibody (G) is virtually identical to that with the ΔNp63-specific antibody Ab-1 (H) (× 100). (I and J) Immunostaining of β-catenin: (I) normal β-catenin expression with homogeneously positive staining at the cell membrane preserved in an LPN tumour (× 200) and (J) reduced (heterogeneously positive) β-catenin expression in a muscle-invasive carcinoma (× 200).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376335&req=5

fig1: Representative photomicrographs of immunostaining for p63, ΔNp63, and β-catenin in urothelial tissues. (A–F) Immunostaining of p63 with the 4A4 antibody that recognises all isoforms of p63: (A) intense staining in normal urothelium (× 200), (B) intense staining in an LPN tumour (× 200), (C) gradual diminution of p63 expression towards the superficial cell layers in an LPN tumour (× 100), (D) weak staining in a high-grade muscle-invasive carcinoma (× 200), (E) loss of staining in a high-grade muscle-invasive carcinoma (× 200), and (F) weak staining in CIS (× 200). (G and H) Immunoreactivity with the 4A4 antibody (G) is virtually identical to that with the ΔNp63-specific antibody Ab-1 (H) (× 100). (I and J) Immunostaining of β-catenin: (I) normal β-catenin expression with homogeneously positive staining at the cell membrane preserved in an LPN tumour (× 200) and (J) reduced (heterogeneously positive) β-catenin expression in a muscle-invasive carcinoma (× 200).
Mentions: We initially evaluated p63 protein expression on normal urothelium and urothelial tumour tissues. Immunoreactivity for p63 was localised to nuclei of normal and neoplastic urothelial cells. Except the urothelium, normal tissues of the kidney, ureter, and urinary bladder were negative for p63. In normal urothelium, almost entire basal and intermediate cells (4–5 layers from the basement membrane) showed intense staining, but immunoreactivity was undetectable in umbrella cells (Figure 1AFigure 1

Bottom Line: At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues.Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms.Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.

ABSTRACT
p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a Delta N-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues. In cultured cells, Delta Np63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

Show MeSH
Related in: MedlinePlus