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

Twenty-eight primary small cell carcinomas of the cervix uteri were examined immunohistochemically for overexpression of p53 protein and c-erbB-2 protein. Twenty-one per cent of the cases showed positive immunostaining for p53 protein, whereas no staining was observed using the antibody against c-erbB-2. Our results indicate that altered expression of p53 protein may be involved in the development of small cell carcinoma of the cervix uteri.
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PMID:Overexpression of p53 protein and c-erbB-2 protein in small cell carcinoma of the cervix uteri. 810 76

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.
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PMID:Loss of retinoblastoma protein expression is frequent in small cell neuroendocrine carcinoma of the cervix and is unrelated to HPV type. 1045 2

A new cell line (SKS) established from ascites of a patient with neuroendocrine small cell carcinoma of the uterine cervix had a good tumorigenicity and caused marked peritoneal dissemination, and was also highly sensitive to gemcitabine in an in vitro chemosensitivity test. SKS cells were small round cells with a high nuclear/cytoplasmic (N/C) ratio and grew into colony-like aggregates, forming spherical aggregates of floating cells. The population doubling time was 44 h. The number of chromosomes ranged from 50 to 56. On examination of the ultrastructure, membrane-bound dense-core neurosecretory-type granules were observed in the cytoplasm. Neuron-specific enolase (NSE) was immunocytochemically positive in the cytoplasm, and 9.3 ng/ml of NSE was detected in the cell culture supernatant. Human papillomavirus was not detected. In the p53 gene, a 3-bp deletion, AAC (Asn), was detected at codon 131 in exon 5. SKS exhibited good tumorigenicity, and the tumor doubling time was 11 days. Intraperitoneal injection of the cells caused peritoneal dissemination, and marked ascites formation was observed. SKS was highly sensitive to gemcitabine, and the 50% growth inhibitory concentration was 30 nM. SKS cells are useful as a model of neuroendocrine small cell carcinoma of the cervix, and chemotherapy using gemcitabine may possibly be effective in this malignancy.
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PMID:Establishment and characterization of a new cell line (SKS) from neuroendocrine small cell carcinoma of the uterine cervix and its chemosensitivity. 1140 6

Twenty-three patients with primary small cell carcinoma of the uterine cervix are presented. Their ages ranged between 23 and 63 years (average, 43 years). Blood spotting or vaginal bleeding was the most common clinical presentation. Histologically, the tumors were densely cellular and showed trabecular nesting or a sheet-like pattern. The neoplastic cells had scant cytoplasm, round nuclei, absence of nucleoli, and finely dispersed chromatin. Nuclear molding, single cell necrosis, and high mitotic activity were found in all tumors. There was a minor component of large cell neuroendocrine carcinoma in three cases, while foci of adenocarcinoma were identified in two cases. Immunohistochemical studies were performed in all 23 tumors which showed immunoreactivity for cytokeratin. Ten small cell carcinomas were immunoreactive for chromogranin, 13 for synaptophysin, and 10 expressed p53 protein. Treatment modalities included hysterectomy alone or combined with chemotherapy and/or radiation therapy. A few patients received chemotherapy and/or radiation alone. Follow-up information was obtained in 22 cases; 15 patients died of tumor between 6 and 43 months, while seven patients have remained alive 12 to 273 months. One patient was lost to follow-up. Small cell carcinoma of the cervix is a highly aggressive neoplasm. However, early diagnosis and combined therapeutic modalities may lead to longer survival in some patients. Although the use of immunohistochemistry may be helpful in the diagnosis, small cell carcinoma still remains a morphologic diagnosis.
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PMID:Small cell carcinoma of the cervix: a clinicopathologic and immunohistochemical study of 23 cases. 1247 83

Cadherins are tissue-specific cell adhesion molecules that function as tumor suppressors. Analysis of cadherin expression is useful for differentiation of tumor histogenesis, and because they serve as markers of tumor behavior and prognosis. Since the pattern of cadherin expression is not well characterized for small cell carcinoma of the cervix, we examined cases of these tumors for expression of cadherins, and two other oncoproteins p53 and BCL2. Four cases of small cell neuroendocrine carcinomas were identified from the Gynecologic Oncology Service with diagnoses confirmed by immunohistochemistry for neuroendocrine markers. Archival paraffin blocks were studied by heat-enhanced immunohistochemistry using commercially available antibodies specific for E-cadherin, P-cadherin, and N-cadherin, p53, and BCL2. Sections were examined for specific membrane staining of cadherins, nuclear staining of p53, and cytoplasmic staining of BCL2. E-cadherin was expressed in three of four cases, P-cadherin in one of four, and N-cadherin in none of four cases. P53 was expressed in one of four cases and BCL2 in one of four cases. The four cases showed three different patterns of immunohistochemical staining for the five oncoproteins. Specifically, two cases expressed E-cadherin only; one case lacked all three cadherins, was negative for BCL2, and was only positive for p53; and one case expressed E- and P-cadherin and BCL2. Prior studies of other neuroendocrine and small cell tumors of other organs showed E-cadherin expressed in 98% (42 /43), N-cadherin in 65% (28/43), and P-cadherin in 40% (17/43) of cases. Additionally, one case of vaginal small cell carcinoma showed expression of all three cadherins. The only significant difference between cervical primaries and other primary sites is that N-cadherin was not detected in our four cases vs. 65% expression in other sites (P < 0.001). We conclude that cadherin and oncoprotein profiles in small cell carcinoma of the cervix are different in the four cases analyzed. Additional cases need to be studied to determine the specificity and frequency of these oncoprotein profiles for small cell carcinoma of the cervix. These may possibly represent different oncogenic pathways in development of small cell cancer of the cervix. Also, our results suggest that N-cadherin may be a tumor suppressor gene in these tumors.
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PMID:Expression of cadherins, p53, and BCL2 in small cell carcinomas of the cervix: potential tumor suppressor role for N-cadherin. 1265 31