These results suggest that changes in DNA encoding p53 may not represent primary oncogenic effects but instead represent genetic changes related to tumor progression.
Low-grade lymphoma of small lymphocytic type disclosed p53+ large cells (paraimmunoblasts) that may play a role in tumor progression in this lymphoma subtype. p53 was also strongly expressed in the nuclei of Reed Sternberg cells from 19 of 37 cases of Hodgkin's disease, including six cases of mixed cellularity, and 13 cases of nodular sclerosing type.
These studies reveal that p53 contributes to a metabolically regulated G1 check-point, and they provide a model for understanding how abnormal cell cycle progression leads to the genetic rearrangements involved in tumor progression.
Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.
These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia.
The purpose of this study therefore was to investigate the clinical value of p53 and Ki67 as markers for tumour progression in BE, and at the same time test the validity of the concept of a metaplasia-dysplasia-carcinoma sequence in BE by correlating the expression of these markers with various grades of dysplasia.
Our results yield two implications: that p53 alterations have a crucial and early role in gastric carcinogenesis of intestinal type, likely acting at the transition step between metaplasia and dysplasia; and that the alterations are mainly associated with tumor progression in cancer of diffuse type.
To further examine the idea that neoplastic progression is associated with mutations in the p53 gene, we analyzed matched primary and metastatic tumor samples.
Altogether, N-ras p21 alterations are registered at earlier stages than p53 alterations in melanoma development and may be of aetiological importance, whereas p53 alterations may be associated with tumour progression in the late stages.(ABSTRACT TRUNCATED AT 250 WORDS)
We demonstrated p53 protein expression in 33% of naevi (17 out of 51), 35% of primary melanomas (20 out of 58), and 70% of metastatic lesions (15 out of 21). p53 expression in benign lesions was weaker than in malignant lesions in intensity and percentage of cells staining. p53 protein expression in melanomas increased in intensity and percentage of cells staining with tumour progression.
The high frequency of mutations of the p53 tumor-suppressor gene in human cancers, including primary brain tumors, suggests that p53 plays a critical role in carcinogenesis and tumor progression.
Cross-talk pathways between these two nuclear proteins are being delineated, implying potential links between p53 and pRB in cell cycle control, apoptosis, and tumor progression.
The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein product(s) of the mutated p53 tumor suppressor gene are associated with tumor progression in patients with T1 bladder cancer.
Mutant conformation of the p53 gene is associated with cell proliferation and tumour progression, and in most cases implies p53 stabilization, which renders the p53 protein detectable through the use of immunohistochemical techniques. p53 expression is a frequent finding in high grade lymphomas of either B or T cell lineage, having been detected in 30% of cases in our series.