Introduction

• belongs to a family of p53-related nuclear transcription factors that includes p53, p73 and p63. PMID: 16271066

• a growth-regulated protein in vascular smooth muscle cells and is present at high levels in human atherosclerotic plaque. PMID: 11602183

• a recently identified gene, maps to chromosome region 1p36.3, which is frequently deleted in a variety of solid tumors. PMID: 11323391

• a novel gene that has high sequence homology and similar gene structure to the tumor suppressor gene p53. PMID: 10773878

Normal Expression

• p73 protein was found immunohistochemically to be distributed in the basal cells of the epidermis, columnar basal cells in the hair follicle and peripheral cells without lipid droplets in the sebaceous and meibomian glands. PMID: 15598310

• By use of immunohistochemical analysis, nuclear staining of p73 protein was detected in a subset of normal mucosa, buccal epithelial dysplasia (ED), and squamous cell carcinoma (SCC) specimens. PMID: 15390192

• p73 immunostaining was nuclear and restricted to epithelial cells of certain organs such as squamous epithelium of the epidermis and transitional epithelium of the bladder. The expression was also observed in certain specialized glandular epithelia such as acinar cells of breast and parotid gland. PMID: 14654547

• p73 gene, a homologue of the tumor suppressor gene p53, was expressed in the nucleus of the human thymic epithelial cells (TECs) in vivo and in TEC lines in vitro. PMID: 11897798

• a homologue of p53 gene, is expressed in several normal tissues including central nervous system. PMID: 11445838

• p73 was biallelically expressed in all fetal tissues, except in brain, where differential expression of the two parental alleles was observed. Biallelic expression of p73 was also observed in paired samples of ovary cancer and Wilms' tumor. PMID: 10760569

• biallelic expression of p73 occurs in normal bone marrows, some AML samples, and specific cell lines. PMID: 10400412

Abnormal Expression

• Cytoplasmic p73 was increased in the primary tumor compared with the distant or adjacent mucosa (p<or=0.0001). Nuclear (p=0.02) and cytoplasmic (p=0.003) p73 was higher in irradiated distant mucosa samples than in unirradiated ones, and nuclear p73 tended to be increased in irradiated primary tumors compared with unirradiated ones (p=0.06). PMID: 16750334

• the first demonstrating the presence of mutations in p73 gene in acute myelogenous leukemia. PMID: 15849769

• p73 protein was expressed strongly in tumor cells in basal cell carcinomas and in the basal cell-like cells in seborrheic keratosis, and weakly or negatively in the squamous cell-like cells in seborrheic keratosis and in the tumor cells in squamous cell carcinomas. PMID: 15598310

• altered expression of the p73 gene has been reported in neuroblastoma, lung cancer, prostate cancer and renal cell carcinoma. PMID: 15385938

• p73 protein is overexpressed and accumulates in the nuclei of HCV-associated HCCs and may play a role in HCC development. PMID: 11991598

• p73 Delta 2 was the principal over-expressed isoform in the majority of cases of vulval SCC and often the sole form expressed in SCC. Over-expression of p73 was associated with expression of HPV-encoded E7 or with hypermethylation or mutation of p16(INK4a) in HPV-negative cases. PMID: 11720444

• expression of p73 is markedly enhanced during differentiation of myeloid leukemic cells and that leukemic blasts from patients show an increased expression of the shorter p73 isoforms (gamma, delta, epsilon, zeta). In particular the epsilon isoform is only expressed in leukemic cells and completely absent in mature myeloid cells. PMID: 11027640

• p73alpha was detected in 6 of 12 benign tumours, and only 1 adenoma expressed 3 splice variants. p73 protein was expressed in 9 of 16 ovarian cancer specimens, in all cell lines and in 1 of 3 borderline tumours. PMID: 10962441

• In 87% of the cases (52/60) p73 expression in tumour was more than twice as high as that in paired normal lung tissues, and the difference between p73 expression in tumour and normal lung tissue was significant (P < 0.0001). PMID: 10408409

• p73 has been mapped at chromosome 1p36.3, a region frequently deleted in breast cancer, neuroblastoma and other malignancies. PMID: 10371354

Diagnostic & Therapeutic Value

• functional impairment of p73 could be involved in the development of thyroid malignancies, defining p73 as a potential therapeutic target for thyroid cancer. PMID: 14522906

• These results reveal an association of p73 overexpression with advanced ovarian carcinomas which may suggest the p73 overexpression as an indicator of poor prognosis. PMID: 12928725

• overexpression of p73 independently predicted poor prognosis in the patients with colorectal cancer. PMID: 11801554

• p73 expression plays a role in inducing tumour recurrence, and that analysis of the expression is useful in evaluating the clinical course of colorectal carcinoma post-surgery. PMID: 11675903

• p73 overexpression is a molecular alteration that could be implicated in the tumorigenesis of breast carcinomas and, eventually, in a poor clinical behavior. PMID: 11510689

• The protein p73 is overexpressed by a subset of hepatocellular carcinoma (HCCs) and could serve as a useful indicator of prognosis in patients with this disease. PMID: 10393724

Review Articles

• p73: a chiaroscuro gene in cancer. PMID: 17428654

• The role of p73 in hematological malignancies. PMID: 16541141

• p73 induces apoptosis by different mechanisms. PMID: 15865927

• p73-induced apoptosis: a question of compartments and cooperation. PMID: 15865923

• p73 in apoptosis. PMID: 11595834

Applications

Immunocytochemistry (ICC)

• p73 overexpression was observed in 58% of pediatric patients as demonstrated by immunocytochemistry and Western blot analysis. PMID: 15649410

Immunohistochemistry (IHC)

• we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. PMID: 15161684

• Expression of p73 protein was evaluated by immunohistochemistry in 221 primary colorectal cancer patients, including 58 patients with matched normal mucosa and metastases in the regional lymph nodes. PMID: 11801554

Western Blot (WB)

• p73 expression was examined by immunohistochemistry and western blot analysis on 56 primary colon carcinomas with matched normal mucosas. PMID: 12865464

• We also examined p73 expression by semi-quantitative reverse transcription-PCR as well as by Western blot analysis and DNA methylation study of the CpG island in exon 1 in ovarian cancer tissues and cell lines. PMID: 11051237