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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This chapter has briefly reviewed the development and progression of peripheral-type adenocarcinoma of the lung, focusing particularly on bronchioloalveolar carcinoma consisting of the nonmucus-producing cell type with or without sclerosis. Histoloical examination reveals that scar cancers are rare except in cases of diffuse pulmonary fibrosis and that many nonmucus-producing bronchioloalveolar carcinomas appear to develop from atypical adenomatous hyperplasia, which can be called adenoma or very well-differentiated adenocarcinoma, and to progress stepwise. Stepwise progression in malignancy can be disclosed not only by cytological and histological examination but also by proliferative activity of the tumor, such as mitotic activity, the percentage of DNA-synthesizing cells and the frequency of proliferating cell nuclear antigen-positive cells, the mean nuclear DNA content of tumor cells and occurrence of aneuploid cell lines, and abnormalities of oncogenes (c-Ki-ras, myc family, and c-erbB2), such as point mutation, rearrangement, amplification, and tumor suppressor genes (point mutation and deletion) such as p53.
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PMID:The development and progression of adenocarcinoma of the lung. 770 84

Accumulation of the tumour suppressor gene p53 product due to a gene mutation is frequently seen in human carcinomas, including lung carcinoma. Another indirect mechanism involving p53 in malignant growth relates to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild-type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo-alveolar carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM-1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty-six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow-up of 12-176 months, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 protein accumulation and the presence of HPV DNA was found.
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PMID:p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis. 855 Feb 45

Atypical adenomatous hyperplasia (AAH) of the lung is a putative precursor of bronchoalveolar carcinoma (BAC). To define the steps in its development and to clarify at which stage critical cellular events occur, we studied 65 lesions of AAH, early BAC, and overt BAC by morphometric analysis and immunohistochemical evaluation of expression of p53 protein and carcinoembryonic antigen (CEA). Both the nuclear area and lesion size increased from AAH to early BAC and to overt BAC; the standardized variation of nuclear area was smallest in overt BAC. Discriminant analysis using these morphometric parameters revealed high accuracy rates for the respective categories. Analysis of distribution of lung lesions in terms of nuclear area and lesion size yielded effective, potentially diagnostic cutoff values for distinction between AAH and early BAC. Both p53 and CEA expression tended to increase with the advance of atypia grade. In particular, high-level p53 expression was strongly correlated with overt BAC. These findings indicate that our classification of lung lesions is reproducible and thus useful for analyzing the development of BAC. Furthermore, some kinds of p53 gene abnormalities that are correlated with high-level p53 expression likely play an important role in the progression of early to overt BAC.
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PMID:Atypical adenomatous hyperplasia and bronchoalveolar lung carcinoma. Analysis by morphometry and the expressions of p53 and carcinoembryonic antigen. 923 46

The p53 gene has been implicated in the pathogenesis of lung cancer as a tumor suppressor gene. Aberrations of the p53 gene (exon 6-8) was examined in 34 surgical specimens of lung cancer with single-strand-conformation-polymorphism analysis of polymerase chain reaction products. Structural abnormalities of the p53 gene were observed in 30 tumor specimens (88.2%), i.e, in 10 of the 12 specimens with squamous cell carcinoma, 8 of the 10 with adenocarcinoma, all the 3 small cell carcinoma, the only one large cell carcinoma, all the 5 alveolar cell carcinoma and all the 3 adenosquamous carcinoma. The aberrations of the p53 gene were not limited to a particular histological type or clinical stage and were not associated with degree of differentiation or history of heavy smoking. It is suggested that high mutation rate of the p53 gene may participate in the genesis of lung cancer. In this study, multiple primer polymerase chain reaction method was applied to detect the human papillomavirus DNA (HPV DNA) in human lung cancer. Only 4 of these 34 specimens were HPV DNA positive, and they were all of squamous cell carcinoma, 3 of them had p53 mutation.
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PMID:[Point mutation of p53 and detection of human papillomavirus DNA in bronchogenic carcinoma]. 873 28

The prognosis of operated patients with non-small cell lung cancer (NSCLC) is poor despite thorough pre-operative staging. An improved preselection is needed of patients likely to profit from surgery. This study was undertaken to evaluate the prognostic significance of nuclear p53 overexpression in a cohort of 247 surgically treated patients with NSCLC. It showed that the prevalence of immunohistochemically detectable p53 overexpression varied between different tumour types. p53 overexpression was equally frequent in large cell carcinoma (53 per cent) and in squamous cell carcinoma (54 per cent), but significantly less frequent in adenocarcinoma (34 per cent; P = 0.009). p53 overexpression was particularly rare in bronchioloalveolar carcinoma (positivity in 1 of 17 cases). These variations may reflect aetiological differences between the histological subtypes. p53 overexpression was also associated with high tumour grade (P = 0.0157) and the presence of lymph node metastasis (P = 0.0259), but not with advanced tumour stage. Survival analysis showed no difference in clinical outcome between p53-positive and p53-negative tumours within 101 node-positive tumours. In contrast, survival time was significantly better in p53-negative tumours than in p53-positive tumours within the group of 113 node-negative tumours (P = 0.032). Stepwise regression analysis showed that p53 overexpression is an independent prognostic factor in node-negative NSCLC.
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PMID:Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma. 877 17

In order to evaluate the alterations of nuclear p53 accumulation in early stage adenocarcinomas of the lung, nuclear p53 accumulation by small-sized peripheral adenocarcinomas of the lung was examined immunohistochemically. Peripheral adenocarcinomas of the lung, 2 cm or less in diameter, have been classified into two groups; one showing replacing growth of the pulmonary alveolar structure and the other showing non-replacing growth. The former group has been subdivided into three microscopic subtypes: type A, localized bronchioloalveolar carcinoma (LBAC); B, LBAC with foci of pulmonary alveolar structural collapse; and C, LBAC with foci of active fibroblastic proliferation. Type C is thought to be advanced carcinoma, which develops progressively from types A and B. Two of 32 (6%) types A and B carcinomas, 37 of 133 (28%) type C carcinomas and 14 of 35 (40%) non-replacement-type adenocarcinomas showed positive nuclear staining for p53. The positive staining frequency was significantly higher for type C than for types A and B (P < 0.05). These results suggest that nuclear p53 accumulation occurs in the transition from the early to advanced stages of replacement-type adenocarcinoma development and it may be a clinically useful indicator of the degree of tumor malignancy.
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PMID:Nuclear p53 accumulation by small-sized adenocarcinomas of the lung. 887 3

Reactive atypia of alveolar epithelium occurs in many types of lung injury and may sometimes raise suspicions of adenocarcinoma or bronchioloalveolar carcinoma. To assess whether there is sufficient difference in the frequency of p53 protein immunopositivity in these lesions to provide a practical basis for differentiating malignancy from reactive atypia, we immunostained 110 malignant and inflammatory/fibrotic lung specimens for p53 protein. Paraffin-embedded sections were immunostained with p53 protein antibody (clone BP53-12; BioGenex, San Ramon, CA) and standard capillary gap (Microprobe; Fisher Scientific, Fairlawn, NJ) avidin- biotin complex technique with antigen retrieval solution. Percent of immunopositive cells was semiquantitatively categorized as follows: 0%, less than 1%, 1% to 10%, 10% to 50%, more than 50%. Of reactive atypias, 94% are negative or show p53 immunopositivity in less than 10% of cells. Of p53 positive malignancies, 86% are positive in more than 10% of cells. When p53 immunopositivity occurs in more than 10% of atypical cells, the lesion is usually a malignancy, primarily adenocarcinoma. Most reactive atypias are immunopositive in less than 10% of atypical cells. Important caveats were noted. Rare reactive atypias are p53 immunopositive in greater than 10% of cells. Bronchioloalveolar carcinomas are infrequently p53 immunopositive. Therefore, this approach would be less useful in their differentiation from reactive atypias.
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PMID:Potential utility of p53 immunopositivity in differentiation of adenocarcinomas from reactive epithelial atypias of the lung. 891 31

Multifocal alveolar hyperplasia associated with pulmonary lymphangioleiomyomatosis is reported in a 21-year-old woman with tuberous sclerosis. Beside the cystic lesions of lymphangioleiomyomatosis, the tomography showed nodules up to 8 mm in both upper lobes. A proliferation of type II pneumonocytes and Clara cells lining the alveolar walls in an adenoma-like pattern was observed. Nuclear atypia, mitoses and necrosis were not observed, providing evidence against multicentric bronchioloalveolar carcinoma or micronodular atypical alveolar adenomatous hyperplasia. Whereas the lymphangioleiomyomatosis lesions showed strong positivity for HMB45 and expressed oestrogen and progesterone receptors, the alveolar hyperplasia was negative for these markers as it was for carcinoembryonic antigen, p53 and MIB1 antibodies. Multifocal alveolar hyperplasia in tuberous sclerosis is probably a benign hamartomatous lesion in our case without progression on a 2-year follow-up. Its histogenesis is unknown, but is possibly related to chromosome instability.
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PMID:Multifocal alveolar hyperplasia associated with lymphangioleiomyomatosis in tuberous sclerosis. 920 62

In this review, we focus on a number of developments pertaining to lung cancer diagnosis, entirely restricted to those parameters assessable by light microscopy. A number of discrete areas of interest stand out in 1996 related to the pathology of lung cancer. Aberrant p53 expression continues to be debated as an independent prognostic factor in nonsmall cell carcinoma. Neuroendocrine differentiation may be an independent prognostic factor in nonsmall cell carcinoma and new associations with the protein product of the bcl-2 oncogene have been described. Angiogenesis continues to arise as a predictor of metastatic potential in lung cancer. Finally, we review conceptual aspects of carcinogenesis from atypical adenomatous hyperplasia to bronchioloalveolar carcinoma, in addition to a variety of individual tumor-related issues associated with progression, response to chemotherapy, and survival.
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PMID:Pathology of lung cancer. 926 9

Because bronchioloalveolar carcinoma (BAC) commonly displays bland cytologic appearance, there is a good potential for misinterpretation. The aim of this study was twofold: one was to identify the most reproducible cytomorphologic features to distinguish BAC from conventional lung adenocarcinoma (CLA) on fine-needle aspiration (FNA), and the other was to investigate the staining characteristics of these two variants of lung carcinoma with P53 tumor suppressor gene immunostain and their potential value in the distinction between the two entities. Cytology records of 13 histologically documented BACs was retrieved: 7 FNA, 3 bronchial washing/bronchial brushing (BW/ BB), and 3 scraping smears of surgical specimens. Two cases had both FNA and BW/BB material. Immunostains for P53 protein, carcinoembryonic antigen (CEA), and Ki67(MIB-1) monoclonal antibodies were performed on 13 BACs (FNA cell blocks and tissue) and on 11 FNA cell blocks of CLA. Cytologically, BAC showed uniform cells with abundant, lacy cytoplasm, and bland, folded nuclei arranged singly, in papillary clusters, and sheets. Immunocytochemically, one BAC and one CLA were technically unacceptable. Of the 12 remaining BAC cases, 10 were reactive with CEA, 9 reactive with Ki67 (> 5%), and 4 reactive with P53. Of the 10 remaining CLAs, 9 were positive with CEA, 9 were reactive with Ki67 (> 5%), and 8 were reactive with P53. We conclude that BAC demonstrates distinctive cytologic features, but difficulty may be encountered with well-differentiated CLA, metastatic adenocarcinoma, and other lesions. Immunocytochemically, CEA and Ki67 do not appear to be discriminate, but P53 may be of value in distinguishing BAC from CLA. Attention to subtle nuclear changes, characteristic grouping, cellular arrangement, and P53 reactivity could enable cytopathologists to accurately diagnose BAC.
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PMID:Bronchioloalveolar carcinoma: diagnostic pitfalls and immunocytochemical contribution. 955 68


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