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)

The diagnostic and prognostic implications of p53 immunostaining have been investigated in 59 pulmonary neuroendocrine tumors, including typical carcinoids (n = 15), so-called "atypical carcinoids" (n = 22), and small cell lung carcinomas (SCLCs; n = 22). Immunocytochemistry was performed on formalin-fixed, paraffin-embedded samples using the monoclonal antibody PAb1801, which has been shown to be suitable for staining fixed and embedded tissue sections. p53 immunoreactivity was restricted to atypical carcinoids (45% of the cases being immunoreactive) and to SCLCs (which were positively stained in 59% of the cases), whereas it was consistently lacking in typical carcinoid tumors. When the group of the so-called "atypical carcinoids" was further reclassified, p53 immunostaining was strictly confined to those cases belonging to the histologically more aggressive subsets (well differentiated neuroendocrine carcinoma subsets II and III). Within the same tumor type, however, p53 immunoreactivity did not correlate with the clinical outcome of the disease and was not predictive of the length of survival. The data indicate that abnormal p53 expression (which is strictly dependent on structural abnormalities of the p53 gene) is detectable in the majority of neuroendocrine carcinomas of the lung and might represent a useful adjunct in the differential diagnosis of pulmonary neuroendocrine neoplasms, particularly in routinely fixed and embedded small bronchoscopic biopsies.
 ...
PMID:Abnormal p53 expression in lung neuroendocrine tumors. Diagnostic and prognostic implications. 136 72

Both carcinoid tumor (carcinoid) and neuroendocrine carcinoma (NEC) are composed of neuroendocrine cells which are positive for chromogranin. The former is a low grade malignancy but NEC is a highly aggressive malignancy. We compared histological differences of those tumors using antibodies to major histocompatibility complex (MHC) class II antigens HLA-DR, proliferating cell nuclear antigen (PCNA), Leu7 (CD57), CEA and P53. Most characteristic differences between those tumors were in the expression of HLA-DR and PCNA. HLA-DR positive capillary endothelial cells were abundant in carcinoid as well as in non-tumorous endocrine organs but sparse in NEC. On the contrary, cells positive for PCNA were 92% in NEC, but 27% in carcinoid. We concluded that carcinoid imitates an endocrine organ in both morphology and function, but NEC deviates far from it.
 ...
PMID:A comparative study of neuroendocrine carcinoma and carcinoid tumor with special reference to expression of HLA-DR antigen and PCNA. 769 Feb 46

Archival specimens of 25 pulmonary carcinoids including 15 cases of typical carcinoid, 9 atypical carcinoids, and 1 large-cell neuroendocrine carcinoma were analyzed for mutations in exons 5 to 8 of the p53 gene. Mutations were identified in 4 tumors, including 3 out of 15 (20%) typical carcinoids and the single large-cell neuroendocrine carcinoma, but none of the atypical carcinomas showed a mutation. The mutations were acquired during tumor development since they were not present in the corresponding nontumorous tissue. All mutations in the typical carcinoids, a tumor type without epidemiological link to cigarette smoking, were G to A transitions. The level of p53 protein was investigated by immunohistochemistry with the polyclonal antibody CM-1. None of the pulmonary carcinoids investigated showed a positive reaction, despite the presence of missense mutations in two cases. Negative staining of carcinoids with mutations was also observed with the monoclonal antibodies pAb1801 and DO-1. Our data suggest that point mutations of the p53 gene are infrequent in pulmonary carcinoids thus contrasting the findings in other histological types of lung cancer, in particular small-cell lung cancer. Moreover, negative immunostaining for p53 is no indicator for the absence of p53 missense mutations in typical carcinoids.
 ...
PMID:Infrequent mutations of the p53 gene in pulmonary carcinoid tumors. 824 38

Eleven tumors of the ampulla of Vater (5 stage IV and 2 stage II adenocarcinomas, 1 stage II papillary carcinoma, 1 neuroendocrine carcinoma, and 2 adenomas, one with foci of carcinoma) were examined for Ki-ras and p53 gene mutations by single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA fragments. Ki-ras mutations were found in one adenocarcinoma and in the adenoma with foci of carcinoma, both involving mainly the intraduodenal bile duct component of the ampulla. Seven cases showed p53 gene mutations: four advanced-stage adenocarcinomas, the papillary carcinoma, the neuroendocrine carcinoma, and the adenoma with foci of carcinoma. Nuclear accumulation of p53 protein was immunohistochemically detected in the morphologically high-grade areas of the five cancers harboring a p53 gene missense point mutation. The adenomas, the two frame shift-mutated cancers, and the adenomatous and low-grade cancer areas of mutated carcinomas were immunohistochemically negative. Our data suggest that in ampullary neoplasia 1) p53 mutations are common abnormalities associated with the transformation of adenomas and low-grade cancers into morphologically high-grade carcinomas, and 2) Ki-ras mutations are relatively less frequent and might be restricted to tumors originating from the bile duct component of the ampulla.
 ...
PMID:Neoplasia of the ampulla of Vater. Ki-ras and p53 mutations. 847 92

Neuroendocrine tumors of lung, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC) constitute a spectrum of malignancies in which the pathologist at times has difficulty in discerning tumor subtype and aggressiveness in a reproducible fashion. Therefore, 59 primary neuroendocrine lung tumors including 10 TCs, 26 ACs, 15 LCNECs, and 8 SCLCs were selected from cases collected from 1976 to 1988 and immunostained for p53 protein. All of these tumors were also genotyped for specific point mutational damage affecting p53 (exons 5, 7, and 8; with ACs additionally sequenced for p53 exon 6); 13 tumors for K-ras-2 (exon 1); and 31 tumors for c-raf-1 (exon 15) growth-regulatory genes. Genotyping was performed on topographically selected, minute tumor samples removed from unstained formalin-fixed, paraffin-embedded tissue sections (topographic genotyping) using polymerase chain reaction and direct sequencing. The distribution of p53 immunohistochemical staining had four patterns: negative in TCs, one-half of ACs, 3 of 15 LCNECs, and 1 of 8 SCLCs; less than 10% but more than five tumor cells per 10 high power fields (focal) in a subset (7 of 26) of aggressive ACs; 10 to 49% of tumor cells (patchy) in a subset (6 of 26) of ACs with a higher grade of aggressiveness; and 50 to 100% of tumor cells (diffuse), exclusively seen in LCNECs (12 of 15) and SCLCs (7 of 8). Three patterns of immunohistochemical staining intensity of p53 protein were seen: negative, weak or mild, and moderate to marked. SCLCs and LCNECs accounted for cases of moderate to marked staining and were the only ones to have mutations in p53 exons 5, 7, or 8. No mutations were found in AC and TC, showing absent to weak staining and no staining, respectively. The difference in distribution and staining intensities between LCNEC and SCLC compared with AC and TC was statistically significant (P < 0.001). Patients having AC with patchy p53 immunostaining usually had survival limited to 3 years, whereas those having AC with focal p53 immunostaining subsequently developed metastatic or recurrence of AC disease (P < 0.05). The absence of point mutations in cases with patchy or focal immunostaining suggests increased expression of wild-type p53 tumor suppressor protein likely in response to growth deregulation in a more aggressive subtype of AC. A novel hypothesis is presented in regard to these findings. K-ras-2 and c-raf-1 gene sequence analysis showed no evidence of point mutational change in any of the tumors studied. The TC and AC categories are therefore genetically distinct from the higher grade neuroendocrine SCLC and LCNEC. Immunohistochemistry for p53 on AC lung tumors may be helpful to delineate cases at higher risk for aggressive behavior. Additionally, although LCNEC is categorized as a non-small-cell carcinoma, it is more akin genetically and immunohistochemically to SCLC.
 ...
PMID:Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome. 862 22

Endocrine ductal carcinoma in situ (E-DCIS), first characterized by Cross et al. in 1985, is an uncommon entity, and there is little information on its pathobiologic features and natural history in the literature. This report describes the largest series of 34 cases: 14 cases were pure in situ (group A), and 20 were accompanied by an invasive component (group B). All except three patients were over the age of 60 years, with the mean being 69.5 years for group A and 72.6 years for group B. Except for six patients in group A who had nipple discharge, all had a breast mass. On follow-up, one of five group A patients developed local recurrence 5 years after mastectomy, and two of seven group B patients developed another invasive primary in the contralateral breast. Histologically, E-DCIS showed expansile intraductal growths forming solid sheets and festoons traversed by delicate fibrovascular septa. Accumulation of basophilic mucin might be found within the growth and the fibrovascular septa. There were variable degrees of stromal sclerosis. In some cases, the solid intraductal cellular proliferations were focally punctuated by microglandular spaces and rosettes. Comedo necrosis was absent. Intraductal papillomas were found in the immediate vicinity of the tumors in 18 cases and invariably showed pagetoid involvement by E-DCIS. Pagetoid spread into the adjacent ducts and ductules was also a common feature (17 cases). The tumor cells were polygonal, oval, or spindly, often with eccentrically placed, bland-looking, ovoid nuclei and abundant eosinophilic granular cytoplasm. Intracellular mucin was commonly demonstrable. Immunostaining for myoepithelium using muscle-specific actin antibody confirmed the in situ nature of the E-DCIS component. The majority of tumor cells showed strong staining with the neuroendocrine markers chromogranin, synaptophysin, and neuron-specific enolase (monoclonal). Immunostaining also dramatically highlighted the pagetoid spread into the papillomas and ductules by outlining the tumor cells between the negatively stained residual ductal epithelium and myoepithelium. All cases were immunoreactive for estrogen and progesterone receptor, but not p53 and c-erbB2. The Ki-67 index was < 5%. Ultrastructural studies on four cases showed many dense-core neurosecretory granules and larger mucigen granules. In group B cases, the invasive component, which comprised 5-95% of the tumor, included colloid carcinoma, 12; "carcinoid" tumor, 3; mixed "carcinoid"/colloid carcinoma, 4; and small cell neuroendocrine carcinoma, 1. Neuroendocrine markers were also consistently demonstrable in the invasive component. In conclusion, E-DCIS is predominantly a disease of older women that is frequently accompanied by papillomas in the vicinity and may present as nipple discharge (an uncommon presentation in the usual forms of DCIS). It can mimic epitheliosis histologically, but the pagetoid spread is a helpful clue to its neoplastic nature. The bland nuclear morphology, lack of necrosis, and biologic marker profile suggest that E-DCIS is a form of low-grade DCIS despite its solid growth pattern. The invasive carcinomas associated with E-DCIS are also neuroendocrine programmed rather than the usual types of ductal carcinomas, suggesting that E-DCIS represents a biologically distinctive category of DCIS.
 ...
PMID:Endocrine ductal carcinoma in situ (E-DCIS) of the breast: a form of low-grade DCIS with distinctive clinicopathologic and biologic characteristics. 871 93

We have previously identified an inverse relationship between p53 and retinoblastoma protein (pRb) immunoreactivity in non-small cell carcinoma of the cervix. Because pRb is infrequently expressed in small cell carcinoma of the lung, we analyzed 25 small cell neuroendocrine carcinomas of the cervix to test the hypotheses that 1) lack of pRb expression is associated with the neuroendocrine phenotype in human papillomavirus (HPV)-associated cervical carcinoma and 2) the inverse relationship between p53 and pRb immunoreactivity also occurs in these tumors. HPV type was analyzed by PCR, HPV distribution by in situ hybridization and expression of p53 and pRb by immunohistochemistry. All of the tumors contained HPV sequences, with 13 tumors HPV 16 positive, 11 HPV 18 positive, and 1 HPV 45 positive. In situ hybridization showed large intranuclear dot-like signals in all positive tumors, suggesting viral integration. No multiple infections were identified. Expression of retinoblastoma protein was not detectable in 23 tumors (92%), the remaining two showing only weak, focal expression. Expression of p53 protein was variable in distribution and intensity. It did not correlate with HPV type, and there was no relationship with pRb immunoreactivity. These data indicate that, although there is no reciprocal relationship between p53 and pRb immunoreactivity in these tumors, retinoblastoma protein is infrequently expressed in HPV-containing small cell neuroendocrine carcinoma of the cervix, irrespective of infecting HPV type. This is consistent with the reported findings in small cell carcinoma of the lung and suggests that the small cell neuroendocrine phenotype may be related to the abrogation of retinoblastoma protein function.
 ...
PMID:Loss of retinoblastoma protein expression is frequent in small cell neuroendocrine carcinoma of the cervix and is unrelated to HPV type. 1045 2

This study screened 11 samples of typical carcinoid (TC), 4 samples of atypical carcinoid (AC), 1 sample of large cell neuroendocrine carcinoma (LCNEC), and four metastases for point mutations in exons 5 to 8 of the p53 gene, and exons 1 and 2 of the K-ras. H-ras, and N-ras genes using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) and direct sequencing and by immunohistochemistry for p53. Exon 1 of K-ras was mutated in two samples of low-grade AC and a metastasis from one of these tumors (GAT12 and AGT12, respectively). No mutations in N-ras or H-ras were found. Mutations in exons 5 and 8 of the p53 gene were identified in a high-grade AC and a LCNEC. Positive immunostaining for p53 was present in three samples, with only one genotypic mutation shown (LCNEC). In conclusion, point mutations of the p53 gene were infrequent in these pulmonary neuroendocrine tumors, did not correlate in all samples with immunostaining, and were associated with the higher-grade tumors. Second, the presence of K-ras mutations seems to be associated with the higher-grade carcinomas. Third, N-ras and H-ras mutations were not found with these pulmonary neuroendocrine tumors.
 ...
PMID:Analysis of K-ras, N-ras, H-ras, and p53 in lung neuroendocrine neoplasms. 1047 81

Patients with head and neck cancer are at high risk of developing additional second primary tumors in the aerodigestive tract as a result of the field cancerization phenomenon. In this context, the appearance of a new neoplasm often poses a problem in differential diagnosis between recurrence and new primary tumor. Twelve patients with nasopharyngeal carcinoma (NPC) who received radiation therapy for the primary tumor and developed a second epithelial malignancy in the nasal cavity or nasopharynx during the follow-up period are presented in this report. The differentiation between the 2 entities based on the spatiotemporal relations, histological features, and the status of Epstein-Barr virus in tumor lesions are also presented. Our study showed that the epithelial malignancy after NPC having late-onset or prolonged interval (range, 5 to 18 years), different histological patterns (keratinizing squamous cell carcinoma, neuroendocrine carcinoma, or small cell carcinoma) distinct from the primary NPC (differentiated or undifferentiated nonkeratinizing carcinoma), and absence of Epstein-Barr virus, indicate a newly developed tumor rather than recurrent NPC. Our observations showed for the first time that second primary epithelial malignancy developed in the nasal cavity or nasopharynx years after curative therapy for NPC with a prevalence of 0.4% (12/2,794). Wild-type p53 protein was expressed more often in the original NPC (9 of 12) than in the second tumors (4 of 10), but the significance was not statistically significant (P = .2048). Genomic analysis for p53 mutation and in situ hybridization for human papillomavirus showed negative results, indicating that both important molecular events in NPC or head and neck cancer play a small role in this particular type of newly developed second malignant tumor. More studies are warranted for further clarification for the development of second epithelial malignancies in treated NPC patients.
 ...
PMID:Second primary epithelial malignancy of nasopharynx and nasal cavity after successful curative radiation therapy of nasopharyngeal carcinoma. 1068 38

We reviewed 11 cases of primary thymic neuroendocrine carcinomas with combined features ranging from well-differentiated to poorly differentiated neuroendocrine carcinoma. For 3 asymptomatic patients, tumors were discovered during routine examination. Presentation in the other patients was as follows: Cushing syndrome, 2 patients; chest pain, 3 patients; superior vena cava syndrome, 1 patient; and hypercalcemia and hypophosphatemia, 1 patient. No clinical data were available for the 11th patient. All tumors were located in the anterior mediastinum and treated by surgical excision. The lesions were large and well-circumscribed with areas of hemorrhage and necrosis. They were characterized by areas showing a proliferation of monotonous, round tumor cells adopting a prominent organoid pattern admixed with areas showing sheets of atypical cells with hyperchromatic nuclei, frequent mitoses, and extensive areas of hemorrhage and necrosis. Immunohistochemical studies performed in 6 cases showed strong CAM 5.2 low-molecular-weight cytokeratin positivity in all cases, chromogranin and synaptophysin positivity in 4, Leu-7 in 3, and focal positivity for p53 in 2. Follow-up information for 9 cases showed that all patients died of their tumors between 1 and 4 years after diagnosis. The present cases highlight the heterogeneity of neuroendocrine neoplasms and reinforce the notion that these tumors form part of a continuous spectrum of differentiation.
 ...
PMID:Thymic neuroendocrine carcinomas with combined features ranging from well-differentiated (carcinoid) to small cell carcinoma. A clinicopathologic and immunohistochemical study of 11 cases. 1070 13


1 2 3 4 5 6 7 8 9 10 Next >>