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

Scientific research evaluates the prognostic importance of 53 expression and DNA flow cytometry controversially. To evaluate the prognostic relevance of mutant p53 protein overexpression and DNA flow cytometry in primary breast cancer we correlated these factors with the common prognostic parameters such as tumor size, lymph node status, grading, menopausal status and receptor status. Human breast cancer specimens from 180 previously untreated patients were collected and deep frozen. On each specimen DNA-analysis by Geohde's technique (Partec PAS II) and immunohistochemical evaluation of mutant p53 protein (PAb 1801 and 240, Novocastra Lab., Great Britain) were performed. Besides TNM- and histological classification, estrogen (ER)- and progesterone (PgR) receptor content was recorded. Overexpression of mutant p53 protein was found in 34 (19%) of all specimens. All these 34 tumors were aneuploid (p = 0.007), 86% of them were receptor negative (p 0.0001), 79% had a high tumor grade (p 0.0001), 73% a high S-phase-fraction (SPF) (p = 0.045) and 53% were premenopausal (p 0.0001). Tumor size and node status did not correlate significantly with p53 expression. 27 (15%) out of 180 carcinomas were diploid. There was a significant correlation between ploidy and the tumor grade (p = 0.003) and SPF (p 0.0001), but not correlation between ploidy and tumor size (p = 0.21), node status (p = 0.33) or receptor status (p = 0.18). A low SPF was predominantly found in tumors less than 2 cm in diameter (p 0.0001); no significant correlation was found between SPF, receptor status, tumor grade, node and menopausal status. Mutant p53 protein expression and DNA analysis in combination with common prognostic parameters might help to detect prognostically unfavourable subgroups of breast cancer patients.
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PMID:Mutant p53 expression and DNA analysis in human breast cancer comparison with conventional clinicopathological parameters. 776 41

There is strong association of Barrett's oesophagus (BO) with adenocarcinoma. The sequence of events preceding malignancy appears to be reflux oesophagitis - ulceration - BO - dysplasia. One hundred and five biopsies of heterotopic columnar epithelium were stained for H&E, PAS/Alcian Blue and HID/Alcian Blue for the routine histology and neutral/acidic sialo- and sulphomucin staining. Other sections were silver impregnated by the Grimelius technique. Immunohistochemical techniques were applied for the assessment of the accumulation of p53 protein, "S" phase of the replication cell cycle using proliferating cell nuclear antigen (PCNA), marked for cell differentiation and proliferation using EGF and TGFa. 105 cases of heterotopic columnar epithelium consisted of 74 cases of BO, 25 junctional and 7 corpus mucosa. Dysplastic BO (n = 9) showed similar amount of sulphomucin and endocrine cell number when compared to non-dysplastic. PCNA study revealed a close similarity between dysplastic, indefinite for dysplasia and non-dysplastic, mucosal positive counts. Growth factors activity was significantly higher in dysplastic and indefinite than in non-dysplastic, but no such difference was found between dysplastic and indefinite for dysplasia BO. There was a significant concurrent p53 expression in dysplastic and indefinite for dysplasia BO. In conclusion, the practical utility of mucin stainings, endocrine cell count, assessment of cell proliferation and differentiation by PCNA, EGF and TGFa seems to be limited in differentiation of the dysplastic and indefinite for dysplasia BO. Altered expression of p53, particularly in combination with EGF and TGFa, may be useful in studying these lesions.
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PMID:Barrett's oesophagus: mucin composition, neuroendocrine cells, p53 protein, cellular proliferation and differentiation. 784 25

The ability of exogenous p53 tumor-suppressor and activated N-PAS oncogene to influence differentiation state of human colon carcinoma LIM 1215 cells and their derivatives with acquired resistance to actinomycin D or methotrexate was analysed Introduction of retroviral construct expressing human wild-type (wt) p53 into LIM 1215 cells induced electron microscopic manifestations of enterocytic differentiation, i.e. caused an increase in the numbers of cells with microvilli, desmosomes and glandular-like lumens. Mutations at codons 248 or 273, the most frequent p53 changes in primary colorectal cancer, partially abrogated the ability of p53 to stimulate differentiation of LIM 1215 cells. Human M-PASasp12 showed stronger stimulation of cell differentiation as compared to p53wt. Especially high proportion (> 80%) of cells possessing pronounced manifestations of columnar enterocytic differentiation was observed after introduction of PAS-expressing construct into methotrexate-resistant LIM 1215 cell subline that originally demonstrated higher maturation than parental cell line. In cell subline with two introduced genes, activated PAS and mutant p53His273, the number of differentiated cells was similar to that observed in cell culture containing only PAS-construct. However, these two sublines differed in the quantity of desmosomes as well as in carcino-embryonic antigen (CEA) expression. Comparison of expression of different electron microscopic features of cell differentiation and CEA expression in cell sublines selected for methotrexate-resistance and/or expressing exogenous constructs allows to suppose that p53 tumor-suppressor, PAS oncogene and dhfr gene amplification may lead to somewhat distinct differentiation states.
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PMID:[Stimulation of differentiation of LIM 1215 large intestinal tumor cells during expression of the p53 exogenous antioncogene or the activated ras oncogene]. 857 93

A rare, minor salivary gland tumour of the hard palate in a middle-aged woman was presented. The small (1.0 X 0.5 cm in diameter) hemispherical tumour was well circumscribed with a fine papillomatous surface. Histopathologically, tumour cells with eosinophilic cytoplasm and a large nucleus were single-strand cuboidal and columnar cells, which showed intraductal growth exhibiting a cribriform pattern. The histological features were distinct from adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma because the tumour lacked the neurotropic infiltration, cord-like proliferation and targetoid arrangement. The tumour could not be identified as a typical salivary-duct carcinoma because Roman bridging, papillary projection, and severe cell atypia were not found. Tumour cells were negative for PAS, Alcian blue, mucicarmine, p53, c-erbB-2, CEA, S-100 protein, alpha-smooth muscle actin, lactoferrin or vimentin. About 5% of the tumour cells were positive for proliferating cell nuclear antigen. Taking these factors into account, together with the clinical features, the name low malignant intraductal carcinoma seems appropriate.
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PMID:Low malignant intraductal carcinoma on the hard palate: a variant of salivary duct carcinoma? 877 26

Malignant eccrine spiradenoma (MES) is an exceedingly rare neoplasm of cutaneous adnexal origin. To date, 31 cases have been documented in the literature. We herein report an additional case of MES that arose in longstanding eccrine spiradenoma (ES). A 54-year-old woman was seen for a bluish nodular mass on the right flank that previously had been stable for 7 to 8 years and had recently increased in size and become tender. The excised mass (2.8 x 2.5 x 2.5 cm) had no attachment to the overlying epidermis. Microscopically, 2 to 3 sharply demarcated lobules were surrounded by a markedly thickened and hyalinized fibrous capsule. Of the lesion removed, approximately 20% of the tumor showed typical histologic features of benign ES. In the remaining malignant areas, the typical configuration of benign counterpart, consisting of peripheral rows of small dark basaloid cells and central layers of large pale cells partially forming lumina, was replaced with a massive solid proliferation of large pale cells showing nuclear pleomorphism, prominent nucleoli, increased mitotic activity (reaching 12/10 HPF) and loss of PAS-positive basement membrane. There were multiple foci of florid squamous differentiation in the malignant portion. Cytokeratin, focally S-100 and EMA were expressed in large pale cells, whereas alpha smooth muscle actin and S-100 were positive in small dark basaloid cells. Focal reactivity of CEA and EMA was found in the central lumina. P53 was not expressed in benign areas, whilst in malignant areas an occasional nuclear reaction was disclosed.
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PMID:Malignant eccrine spiradenoma with florid squamous differentiation. 961 Jun 21

Apocrine carcinoma is an uncommon variant of breast cancer. The frequency of bilaterality in patients who have apocrine carcinoma in one breast is not significantly different from that for bilateral mammary carcinomas in general, but bilateral apocrine carcinomas are very uncommon. We report on a bilateral apocrine carcinoma of the breast in a 74-year-old woman. The apocrine differentiation in both tumours was confirmed by the positivity of the cytoplasmic granules for PAS after diastase digestion and immunoreactivity for GCDFP-15 and sialyl-Tn. The tumour in the right breast showed immunohistochemical expression of p53, and a mutation was demonstrated by PCR-SSCP; the tumour in the left breast was negative for p53 on immunohistochemistry, and no mutation was found at the molecular level. c-erbB2 expression was not detected in the right tumour but there was overexpression (at the cell membrane) in the left tumour. Both tumours were aneuploid: the right tumour displayed multiple stemlines, whereas the left tumour had a triploid profile. Using the fluorescence in situ hybridization technique we demonstrated that both tumours displayed chromosome 17 polysomy and numerical abnormalities of chromosome 1, polysomy in the right and monosomy in the left tumour. We conclude that the two tumours are probably independent, as are most bilateral carcinomas of the breast.
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PMID:Bilateral apocrine carcinoma of the breast. Molecular and immunocytochemical evidence for two independent primary tumours. 987 Jun 82

To clarify changes in mucus components during colorectal tumorigenesis, we developed novel monoclonal antibodies (Abs) against carbohydrate chains of human colorectal mucin (HCM) obtained from normal sigmoid and rectal mucosae. A hundred and ninety-nine cases of colorectal carcinoma and 67 cases of tubular adenoma, along with 250 normal colonic tissue samples, were investigated immunohistochemically. The results were compared with clinical stage, survival and MUC2 (core protein of the intestinal type mucin) expression, as well as with the status of the p53 and DCC (deleted in colorectal carcinomas) genes. In the normal colonic epithelium, HCM14 Ab reacted with the cytoplasmic regions of the goblet cells and enterocytes, while HCM21 Ab bound to mucous droplets in the former, suggesting a more mature carbohydrate structure. Both HCM14 and 21 scores were significantly decreased in adenomas and carcinomas. This is in line with an altered PAS-Alcian blue staining, indicating accumulation of mucins with incomplete or abnormal glycosylation in tumors. Levels of HCM14 and 21 binding tended to show a positive correlation with expression of MUC2 and DCC, and a negative association with p53 protein accumulation in carcinomas, although there was no apparent link to Duke's stage or the prognostic outcome. These findings suggest a possible involvement of alterations in mucin carbohydrate in colorectal tumor development. The observed changes may be associated with loss of MUC2 and DCC expression, as well as with p53 protein accumulation.
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PMID:Colonic mucin-carbohydrate components in colorectal tumors and their possible relationship to MUC2, p53 and DCC immunoreactivities. 1072 20

Pathologic diagnosis of pancreatic adenocarcinoma is frequently a challenge, particularly in small biopsies, frozen sections, and in metastatic foci. Here we report a deceptively benign-appearing and morphologically distinctive pattern of ductal adenocarcinoma with prominent microvesicular cytoplasm, giving the cells a foamy appearance similar to that described in the prostate (Am J Surg Pathol 1996;20:419). This variant, which we refer to as foamy gland pattern (FGP), was frequently misdiagnosed in frozen sections or biopsies and its pathologic stage underestimated in surgical specimens. Histologically, the diagnostic features were: (1) white and crisply foamy, "microvesicular" cytoplasm; (2) often basally located and compressed, hyperchromatic nuclei reminiscent of endocervical glands (and so-called "adenoma malignum") or gastric foveolar glands; (3) irregular nuclear contours forming wrinkled (raisinoid) nuclei in some areas; and (4) a distinctive chromophilic condensation of the cytoplasmic material in the luminal aspect of the cells forming a brush border-like zone (BLZ). Histochemically, this BLZ was positive for mucicarmine, alcian blue, and high iron diamine, but not PAS. The remainder of the cytoplasm was negative for all these stains. In contrast, benign mucinous ducts, which constitute the major differential diagnosis, had more homogeneous acidophilic cytoplasm, lacked BLZ, and showed cytoplasmic staining with PAS. Immunohistochemically, the tumor cells were diffusely and strongly positive for CEA and cytokeratin 8 whereas B72.3 staining was focal and weak. MUC1 staining was largely confined to the BLZ. MUC2 was negative. P53 staining was detected in 16 of the 20 cases studied and was strong and diffuse in five. K-ras mutation was detected in 6 of 8 cases studied. The clinical findings in the 20 patients in this study (4 pure and 16 mixed with usual ductal carcinoma) did not appear to differ significantly from those of ordinary ductal adenocarcinoma of the pancreas. Eleven patients were men and nine were women; the mean age was 62 years and the mean tumor size was 4.4 cm. Follow-up information was available in 17 patients of whom 7 were alive at an average follow up of 23 months (range, 7-104 mos), and 10 were dead of disease at a median follow up of 15 months (range, 4-42 mos). The median survival of the four patients with pure FGP was 18 months. The median survival did not appear to be significantly longer than that of the patients with resectable ordinary ductal adenocarcinoma in the authors' experience (109 patients, median survival of 12 mos, p = 0.48). In conclusion, foamy gland pattern of invasive pancreatic ductal carcinoma is morphologically distinctive and is prone to misdiagnosis as a benign process. The pathologic stage is often underestimated as a result of the lack of its recognition and misinterpretation as mucinous ducts. Careful attention to its microscopic features is adequate for accurate diagnosis. Histochemical and immunohistochemical stains are useful in confirming the diagnosis of malignancy in challenging cases.
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PMID:Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant. 1075 96

A 41-year-old female presented in April 1996 with a tumor of the hard palate revealed by increasing left palate pain. Adenoid cystic carcinoma was suspected on clinical and imaging data. Two limited surgical procedures showed a tumor histologically made of small lobules of granular cells, PAS positive and expressing S100 protein, infiltrating some medullary spaces of the palatine bone, consistent with a granular-cell tumour. Pain recurred in the territory of the maxillary branch of the left trigeminal nerve (V2). Imaging showed a tumor of the origin of V2-extending through the foramen rotondum. Two radical interventions in September and in October 2000 showed an infiltrating tumor of the V2 and palatine mucosa, with the same histology. There was no immuno-staining for p53, and less than 5% of nuclei expressed Ki67. Malignant Abrikossof tumors are exceptional, morphologically difficult to differentiate from benign ones, only metastasis proving malignancy. Tumor size above 5 cm, recurrence and infiltrative character are considered pejorative. The value of p53 and Ki67 expression remains controversial. We discuss our observation according to these criteria.
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PMID:[A palate tumor revealed by pain]. 1241 Jan 57

Granular cell astrocytomas (GCA) are an uncommon morphologic variant of infiltrative glioma that contains a prominent population of atypical granular cells. As a rule, they are biologically aggressive compared to similar tumors without granular features. We sought to determine whether GCAs possess distinct genotypic alterations that might reflect their unique morphology or clinical behavior. Eleven GCAs occurring in 7 men and 4 women ranging in age from 46 to 75 years were investigated for genetic alterations of known significance in glial tumorigenesis, including LOH at 1p, 9p, 10q, 17p, and 19q, point mutations of TP53, deletions of p16(CDKN2A) and p14ARF, as well as EGFR amplifications. Tumors included had an infiltrative growth pattern and consisted of large, round cells packed with eosinophilic, PAS-positive granules that varied in quantity, ranging from 30 to 100% of tumor cells. Three tumors were of WHO grade II, one was grade III, and 7 were grade IV lesions. Overall, the tumors showed higher frequencies of LOH at 1p, 9p, 10q, 17p, and 19q than typical infiltrating astrocytomas of similar grades. Losses on 9p and 10q occurred in nearly all cases, including low grade lesions. TP53 mutations were identified in 2 grade IV GCAs, while combined p14ARF and p16(CDKN2A) homozygous deletions were noted in only one grade IV lesion. None showed EGFR amplification. We found no genetic alterations specific for GCA. Instead, it appears that granular cell change occurs across genetic subsets. The high frequency of allelic loss, especially on 9p and 10q, may confer aggressive growth potential and be related to their rapid clinical progression.
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PMID:Granular cell astrocytomas show a high frequency of allelic loss but are not a genetically defined subset. 1274 72


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