Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A precursor lesion of pulmonary adenocarcinoma has not been clearly defined. Previous studies suggested that atypical alveolar cell hyperplasia (AACH) might represent such a precursor lesion. Most previous studies showed an association between AACH and adenocarcinoma in surgical resection specimens. In this study, we searched for the prevalence of AACH and nonatypical alveolar cell hyperplasia (ACH) in a general autopsy population. Cases in which there was clinical or anatomic evidence of pulmonary neoplasia were excluded from the study. In the 100 consecutive autopsies examined, we found four cases of ACH and two cases of AACH. The two AACH lesions showed cytologic atypia and stained positively for p53 and c-erb-2. These findings suggest a possible role for AACH as a precursor lesion of adenocarcinoma of the lung.
 ...
PMID:Prevalence of pulmonary atypical alveolar cell hyperplasia in an autopsy population: a study of 100 cases. 916 Mar 12

The tumour which develops most frequently in mice carrying a p53 Val135 transgene is adenocarcinoma of the lung. We established 10 cell lines from these tumours and investigated their karyotypes by detailed cytogenetic analysis using a complete set of mouse chromosome-specific paints. Consistent loss of chromosome 4 material was noted in 9 out of 10 cell lines; this loss was detected in tetraploid but not diploid cells of the same cell line, suggesting that mouse chromosome 4 plays a critical role in the progression of lung adenocarcinomas. Other frequently observed chromosome aberrations involved chromosomes 7, 5 and 8. Atypical bronchial epithelium was observed together with lung tumours and in tumour-free, apparently normal lungs indicating that mouse lung tumours induced due to the presence of a mutant p53 transgene may develop via pre-invasive lesions and thus may be effective models for the study of lung tumour progression.
 ...
PMID:Genome wide search for genetic damage in p53 transgenic mouse lung tumours reveals consistent loss of chromosome 4. 938 33

To evaluate the importance of mutations of p53 and K-ras genes in the prognosis of patients with non-small cell lung cancer, one hundred and forty-four patients who underwent surgery were studied. DNA was extracted from frozen specimens. Polymerase chain reaction-single strand conformation polymorphism and sequencing were performed to investigate mutations of p53 from exon 5 to 8, and mutations of exon 1 of K-ras. Mutations of p53 gene occurred in 35. 4% of patients, and mutations of the K-ras gene in 8.3%. The overall survival rate of non-small cell lung cancer patients with wild-type K-ras was better than that of patients whose tumors had mutations of K-ras (P=0.0330). Among patients with adenocarcinoma of the lung, the overall survival rate of patients with wild-type p53 was strikingly better than that of patients whose tumors had mutations of p53 (P=0.0234). Multivariate analysis with the Cox regression model of all patients with non-small cell lung cancer and those with adenocarcinoma indicated that mutations of K-ras best correlated with the overall survival rate (P=0.0005 and P=0.0361, respectively). In conclusion, evaluation of mutations of both the p53 and K-ras genes in the lung tumors might be useful for assessing the prognosis, especially in patients with adenocarcinoma.
 ...
PMID:Mutations of p53 and K-ras genes as prognostic factors for non-small cell lung cancer. 947 92

Bronchioloalveolar carcinoma (BAC) is a particular type of adenocarcinoma of the lung which accounts for up to 9 per cent of pulmonary malignancies. The aetiology and pathogenesis of this unique neoplastic disease are still unclear. Three histological subtypes of BAC have been recognized: mucinous, non-mucinous, and sclerosing. Of these, mucinous and sclerosing BAC have a worse prognosis than non-mucinous tumours. The different morphological patterns and clinical outcomes of the subtypes of BAC suggest differences in their biological behaviour. Previous reports have shown that the mucinous form of BAC is characterized by constant mutations at codon 12 of the K-ras gene, whereas the other two histotypes show a frequency of K-ras mutations which is not different from that observed in conventional lung adenocarcinomas. The present study of a series of 51 BACs, previously investigated for K-ras gene mutations, has evaluated the status of two other genes, p53 and FHIT, known to be frequently altered in non-small cell lung cancer. Loss of heterozygosity at microsatellite-containing loci located within the FHIT gene was observed in 22 (43 per cent) BACs. The distribution of FHIT gene abnormalities was not statistically different in the three histological subtypes. p53 mutations were present in 13 (32 per cent) non-mucinous/sclerosing BACs, while no mutations were seen in mucinous tumours (P = 0.039). Correlations with clinicopathological parameters showed that p53 mutations in BACs are associated with more aggressive tumours. No correlations were observed between FHIT or K-ras gene abnormalities and clinicopathological data. In conclusion, these results indicate that FHIT alterations are frequently involved in BAC tumourigenesis and that genetic changes in the p53 and K-ras genes can distinguish between different histotypes of BAC.
 ...
PMID:FHIT and p53 gene abnormalities in bronchioloalveolar carcinomas. Correlations with clinicopathological data and K-ras mutations. 961 74

A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia (AAH) in a 77-year-old woman is reported. Histopathologically, in the resected left upper lobe of the lung, both cancers were diagnosed as well-differentiated papillary adenocarcinoma, and 161 lesions of AAH were also found. Both the cancer lesions and six AAH (greater than 3 mm in diameter) were examined with regard to immunoreactivity of carcinoembryonic antigen (CEA) and p53 gene product, microsatellite instability (MI) and loss of heterozygosity (LOH) on chromosome 9q and 17q by polymerase chain reaction (PCR). Although both cancers expressed CEA, they did not show clonal immunoreactivity for the p53 gene product. Atypical adenomatous hyperplasia expressed CEA weakly and showed no immunoreactivity for p53 gene protein. Both carcinomas showed LOH on chromosome 17q, and one of them showed LOH on chromosome 9q. In six AAH, LOH on chromosome 17q was detected in two tumors, and one of them also showed LOH on chromosome 9q. One AAH, which was negative for LOH on chromosome 17q and 9q, showed MI at D17S791. These results indicated that AAH is a clonal neoplastic lesion with genetic abnormalities and should be called intraepithelial pneumocyte neoplasia, and that each of the numerous papillary lesions in this case was considered to be an independent lesion.
 ...
PMID:A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia. 973 12

Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53, and erbB-2 gene amplification. Pathological material after resection was reviewed to verify histological staging, and patient follow-up was complete in all cases for at least 68 months. Immunohistochemistry of erbB-2 (HER-2/neu) and p53 oncogene expression was performed on two separate paraffin tumor blocks for each patient with normal lung as control. Gene amplification of erbB-2 was measured after DNA extraction from 20-micrometer sections of erbB-2-positive and -negative tumors. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Two adequate blocks of tumor and normal lung were available for 138 (92%) patients. Immunohistochemical identification of expression of p53 was observed in 49 (37%) patients and erbB-2 in 17 (13%) patients. DNA dot blot analyses were performed on 17 erbB-2-positive and 13 randomly selected erbB-2-negative tumors. There was 1 (6%) of 17 erbB-2-positve tumors with 4-fold erbB-2 gene amplification. Actual 5-year survival was 63% and actuarial 10-year survival was 59% for the entire population of 150 patients. Significant univariate predictors (P < 0.05) of cancer death were the presence of symptoms, tumor size >3 cm, poor differentiation, visceral pleural invasion, and p53 expression. Multivariate analysis associated symptoms and p53 expression as independent factors with decreased survival. Thus, this project examined p53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival. Multicenter collection of data should allow the development of a model of cancer recurrence in this most common lung cancer.
 ...
PMID:Localized adenocarcinoma of the lung: oncogene expression of erbB-2 and p53 in 150 patients. 981 29

Thymic carcinoma is an uncommon tumor. Most cases appear to arise de novo, but in rare instances they can arise in thymomas. We report the clinicopathologic features and immunohistochemical profile of five cases of thymic carcinoma accompanied by a component of thymoma. Immunohistochemical studies were performed with the avidin-biotin-peroxidase complex method using monoclonal antibodies to p53(DO7), CD99(O13), epithelial membrane antigen, CD5(NCL-CD5-4C7), vimentin (V9), and cytokeratins 7, 8, 18, and 19. The patients consisted of three men and two women with a median age of 57 years. One patient had myasthenia gravis, and the other four presented with chest symptoms. One patient had concurrent adenocarcinoma of the lung with metastasis. Four of the patients died within 15 months. The thymomas consisted of two large polygonal cell thymomas, two squamoid thymomas, and one spindle cell thymoma. The malignant components included two undifferentiated carcinomas, one spindle cell carcinoma, one squamous cell carcinoma, and one clear cell carcinoma with squamous differentiation. There was no correlation between the histologic types of the thymoma and the thymic carcinoma. In three cases, excluding the two squamoid thymomas, the thymic carcinomas occurred in the necrotic areas of the thymoma. They showed upregulated expression of epithelial membrane antigen and cytokeratins 7, 8, 18, and 19, similar to the so-called "interface phenomenon" described in the invasion front of other types of carcinoma. Increased p53 protein expression was observed in all five carcinomas, and there was loss of CD99+ immature T lymphocytes. Among the thymic carcinomas, only the squamous component of the clear-cell carcinoma stained for CD5, a marker commonly expressed in thymic carcinomas. Paradoxically, a squamoid thymoma, but not its associated spindle cell carcinoma, expressed CD5, suggesting the acquisition of an "aggressive" phenotype by the squamoid thymoma, but with loss of the marker on malignant transformation. One undifferentiated carcinoma acquired vimentin immunoreactivity, whereas four other carcinomas and all five thymomas were negative. In conclusion, thymic carcinoma can arise in any histologic type of thymoma, including spindle cell thymoma, which is generally regarded as a benign neoplasm. The prognosis appears to be poor. Tumor necrosis in a thymoma should alert the pathologist to search for malignant change. The malignant change is commonly associated with increased expression of epithelial membrane antigen, cytokeratin subtypes, or p53 protein, and loss of CD99+ immature T lymphocytes, and is occasionally associated with a change in the expression of CD5 or vimentin.
 ...
PMID:Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile. 985 Jan 73

Synchronous primary lung cancer (SPLC) occurs in up to 0.5% of patients with lung cancer. Among SPLC cases, coexistence of small cell carcinoma (SCLC) and non-small cell carcinoma has been reported in a very small fraction. Futhermore, there have been no reports discussing treatment and prognosis of SPLC presenting with SCLC and NSCLC. We report on two cases of SPLC presenting SCLC in limited stage and operable NSCLC. One patient developed synchronously SCLC and adenocarcinoma of the lung, while the other SCLC and squamous cell carcinoma of the lung. The clonal origin of these synchronous lung cancers was evaluated using immunohistochemical and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses. Both of the patients were diagnosed based on transbronchial lung biopsy (TBLB) and mediastinoscopic biopsy. They were successfully treated with chemoradiotherapy and adjuvant surgery, and are now doing well without any signs of tumor progression for about one year. In both cases, a response of mediastinal lymph node for concurrent chemoradiotherapy was quite different from that of the mass in the lung field. In case 2, p53 mutation was observed in the SCLC tissue, but not in the NSCLC tissue by PCR-SSCP. In both cases, carcinoembryonic antigen was documented in the NSCLC tissue, but not in the SCLC tissue by immunohistochemical staining. This report indicates the importance of the accurate diagnosis of SPLC by employing TBLB and/or media-stinoscopy for the optimal treatment of patients having SPLC presenting with SCLC and NSCLC. Diagnostic criteria and standard treatment of this disease should be established.
 ...
PMID:Synchronous primary lung cancer presenting with small cell carcinoma and non-small cell carcinoma: diagnosis and treatment. 986 5

In order to clarify the morphological and biological characteristics of well differentiated adenocarcinoma of the lung predominantly composed of goblet cells (WDAG), histopathological examinations, including some molecular biological procedures, were carried out using 42 surgical specimens of primary lung carcinoma which were predominantly (>50% of the total cell population) or totally composed of goblet cells. The subjects included 19 men and 21 women, ranging in age from 41 to 81 (mean 60 years old) with predominantly nodular, peripherally located lesions. Ultrastructural examination revealed characteristic apical microvillous filamentous core rootless (AFCR) in some, but not all, cases. Histologically, these AFCR corresponded well with structures stained by phosphotungstic acid hematoxylin (PTAH). The goblet cells of WDAG were divided into PTAH-positive (26 cases) and -negative (16 cases) groups. The PTAH-positive group had larger tumor size, greater number of intrapulmonary and extrapulmonary metastases and shorter disease-free interval. The immunoexpression of p53 protein (60%) and rate of K-ras point mutation (84%) were also higher in the PTAH-positive group. Therefore the goblet cell population of WDAG, though it may appear morphologically homogeneous under light microscopy, is actually composed of heterogeneous groups of cells with different histopathological characteristics and biological behavior.
 ...
PMID:Immunohistochemical, ultrastructural and molecular study of well differentiated adenocarcinomas of the lung predominantly composed of goblet cells. 1002 18

A 66-year-old female patient underwent left upper lobectomy and dissection of the mediastinal lymph nodes. The pathological diagnosis was well-differentiated papillary adenocarcinoma of the lung with metastasis to the mediastinal lymph nodes, p-T2N2MO, stage IIIA. After the operation, she was treated by chemotherapy including lipophilic anticancer compounds (carboplatin and VP-16). The patient unexpectedly showed long survival for 6 years and 2 months without obvious recurrence or metastasis of the cancer. The anticancer compounds were not effective on the recurrent lesions and then she died due to respiratory failure 8 months after recurrence. The autopsy revealed pleural dissemination and intrapulmonary metastasis. Immunohistochemical analysis showed increased multidrug resistance-associated protein (MRP)-positive tumor cells in the recurrent and metastatic lesions, while few MRP-positive cells were apparent in the primary lesion. The MRP-positive cells were accompanied by p53 nuclear accumulation in the carcinoma. This was a case of pulmonary adenocarcinoma with acquired multidrug resistance caused by MRP overexpression and aberrant p53 after chemotherapy.
 ...
PMID:A case of pulmonary adenocarcinoma with overexpression of multidrug resistance-associated protein and p53 aberration. 1092 27


<< Previous 1 2 3 4 5 6 Next >>