Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In an attempt to characterize the molecular alterations of cervical adenocarcinoma, we analyzed 32 paraffin-embedded specimens for the presence of K-ras mutations, p53 overexpression, p16 and Rb protein expression, and the presence of HPV 16 and 18 DNA. Overall 25/32 (78%) of the tumors displayed an abnormality in at least one of these analyses. K-ras mutations were detected by PCR amplification and RFLP analysis in 3 tumors, including 2 at codon 12 and 1 at codon 61. p53 overexpression determined by immunohistochemistry was demonstrated with > 80% of tumor nuclei staining in 4 cases, 10-15% of nuclei staining in 3 cases, and < 1% of nuclei staining in 5 cases. The pattern of staining was diffuse in 6 cases, focal in 1 case, and scattered in 5 cases. Analysis of p16 protein expression in 23 specimens revealed 1 tumor with abnormal staining, while Rb protein expression was determined to be normal in all 25 tumors tested. HPV DNA, detected by PCR with type-specific primers, was found in 16 tumors (50%), including 7 (22%) with HPV 16 and 9 (28%) with HPV 18. There was no correlation among these abnormalities except that the presence of HPV and strong p53 overexpression (> 80% tumor nuclei staining) were mutually exclusive events. Clinical correlation demonstrated that p53 overexpression involving the majority of tumor cell nuclei is characteristic of advanced stage disease, while HPV positivity and activated ras genes are associated with early stage disease.
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PMID:Molecular characterization of adenocarcinoma of the cervix. 903 70

Our purpose was to evaluate the utility of clinicopathological and biological markers prior to treatment in predicting the immediate response to chemotherapy in cervical and endometrial adenocarcinomas. Twelve patients with locally advanced cervical adenocarcinomas and 16 patients with endometrial adenocarcinomas received intraarterial neoadjuvant chemotherapy (NAC) consisting of cisplatin and doxorubicin before surgical resection. The decrease in tumor volume on magnetic resonance imaging (MRI) ([tumor volume before NAC - tumor volume after NAC]/tumor volume before NAC x 100) and the histologic response to NAC were assessed. Five factors prior to NAC (nuclear grade, pretreatment tumor volume, PCNA index, p53 protein expression, and DNA ploidy) were analyzed for correlation with the decrease in tumor volume and histologic response in cervical and endometrial adenocarcinoma, respectively. In cervical adenocarcinoma, patients with higher PCNA index tumor (> or = 40.2%) showed a significantly greater decrease in tumor volume than those with lower PCNA index (P < 0.05). In patients with endometrial adenocarcinoma, those with a smaller tumors (< 30.3 cm3) showed a significantly greater decrease than those with a larger tumors (P < 0.001). Tumors with higher PCNA index (> or = 31.5%) and negative p53 protein expression appeared to respond better than other tumors, but the difference was not statistically significant. Nuclear grade and DNA ploidy were not correlated with decrease in tumor volume either in cervical adenocarcinoma or in endometrial adenocarcinoma. Four cases of effective histologic response (2 complete responses [no microscopic residual tumor] and 2 marked responses [no macroscopic residual tumor]) were noted only in patients with endometrial adenocarcinoma who had a smaller tumor, higher PCNA index, and negative p53 protein expression. Pretreatment tumor volume and PCNA index were the only significant predictive factors (P < 0.05). Results suggest that the PCNA index in cervical and endometrial adenocarcinomas and the pretreatment tumor volume in endometrial adenocarcinoma appeared to be potentially useful in predicting the immediate response to the chemotherapy.
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PMID:Decrease in tumor volume and histologic response to intraarterial neoadjuvant chemotherapy in patients with cervical and endometrial adenocarcinoma. 915 35

The incidence of cervical adenocarcinomas in young women over the last two decades has increased. Even with increasing knowledge of the role of human papillomavirus in the etiology of adenocarcinoma of the cervix, there is a paucity of data concerning the genetic and epigenetic factors that contribute to the histologic features and biologic behaviors of these tumors. Lactoferrin is a basic glycoprotein found in human milk, secondary granules of neutrophils, and many body secretions, and it has been associated with carcinogenesis of the endometrium, breast, and lymphoid systems. In this study, we examined the expression of lactoferrin in normal human endocervical epithelium and in cervical adenocarcinomas in relation to proliferative index, steroid receptor status, p53 protein expression, and apoptosis. Immunohistochemical and in situ studies demonstrated that lactoferrin protein and mRNA were strikingly downregulated upon neoplastic transformation of the endocervix as early as in adenocarcinoma in situ when compared with the prominent expression exhibited by the normal cervical epithelium. Furthermore, neoplastic transformation of endocervical epithelial cells was accompanied by a pronounced stimulation of proliferation and a substantial reduction in the expression of the estrogen and progesterone receptors and p53 but little or no change in the number of apoptotic cells. In conclusion, we identified lactoferrin as a novel cancer-specific marker of endocervical adenocarcinomas that may be useful in the early detection of the disease, prediction of prognosis, and the development of new therapeutic modalities.
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PMID:Neoplastic transformation of the endocervix associated with downregulation of lactoferrin expression. 936 14

The clinical and pathologic features of 17 cases of papillary serous adenocarcinoma of the cervix (PSCC) were studied in women who ranged in age from 26 to 70 years. There was a bimodal age distribution, with one peak occurring before the age of 40 years and the second peak after the age of 65. The presenting symptoms were abnormal vaginal bleeding (11 patients), abnormal exfoliative cervical cytology (four patients), or watery vaginal discharge (two patients). On pelvic examination, eight patients had a polypoid or exophytic cervical mass and two patients had an ulcerated or indurated cervix; no abnormality was detected in seven patients. Two tumors were stage Ia, 12 were stage Ib, two were stage II, and one was stage III. Nine patients were treated by radical hysterectomy and one by simple hysterectomy; six of these patients received postoperative radiotherapy. The other patients received primary radiotherapy. On microscopic examination, all of the tumors had a complex papillary architecture with epithelial stratification and tufting. Six tumors were grade 2/3 and 11 were grade 3/3. All of the tumors had >10 mitotic figures per 10 high-power fields. An intense acute and chronic inflammatory infiltrate was typically present within the cores of the papillae and in areas of stromal invasion. Occasional psammoma bodies were present in three cases. Five of 12 tumors stained positively for p53, with six and nine of 12 tumors, respectively, immunoreactive for carcinoembryonic antigen and CA-125. Seven tumors were mixed with another histologic subtype of cervical adenocarcinoma, most commonly low-grade villoglandular adenocarcinoma. Fifteen patients were followed from 6 months to 11 years (mean 56 months). Six patients died of extensive metastases within 5 years of diagnosis; an additional patient experienced tumor recurrence with malignant ascites 2 years after diagnosis. The most common metastatic sites were pelvic and periaortic lymph nodes; other sites included cervical lymph nodes, lung, peritoneum, liver, and skin. Eight patients were alive without evidence of tumor at last follow-up. Age <65 years, stage >I, tumor size >2 cm, tumor invasion >10 mm, the presence of lymph node metastases, and elevation of serum CA-125 were associated with a poor prognosis. Tumor grade or composition (pure or mixed) did not correlate with patient outcome. Papillary serous adenocarcinoma of the cervix resembles microscopically its counterparts elsewhere in the female genital tract and peritoneum. The tumors can behave aggressively with supradiaphragmatic metastases and a rapidly fatal course when diagnosed at an advanced stage, but the outcome for patients with stage I tumors is similar to that of patients with cervical adenocarcinomas of the usual type.
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PMID:Papillary serous carcinoma of the uterine cervix: a clinicopathologic study of 17 cases. 942 24

Mutant p53 is frequently detected in endometrial and ovarian carcinoma, but it is rare in cervical cancers. Previous reports focused on cervical squamous cell carcinoma, whereas cervical adenocarcinoma was given little attention. We searched for p53 gene mutations in 74 primary cervical adenocarcinomas with known human papillomavirus (HPV) status. Our aim was to evaluate the prevalence of p53 mutations and to investigate their possible role as an independent prognostic factor. We found mutations in 13.5% with a high rate of G:C --> A:T transitions as observed in endometrial adenocarcinoma. As p53 mutations are more frequently detected in malignancies of high grade, high stage, and large size, this molecular event seems to play a role in the progression rather than in the induction of cervical adenocarcinoma. In our series, patients with HPV-negative tumors and patients with mutated neoplasms, irrespective of HPV infection, had a shorter survival. Yet the absence of HPV infection and presence of p53 mutations are not independent risk factors for tumor-related death after adjustment for clinicopathological confounders. The only significant and independent predictors of survival are age of patient, stage of disease, tumor grade, and presence of lymph node metastases.
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PMID:Analysis and clinical implications of p53 gene mutations and human papillomavirus type 16 and 18 infection in primary adenocarcinoma of the uterine cervix. 954 66

Although molecular alterations involved in the development of squamous cell carcinoma of the cervix have been extensively described, these genetic changes have not been as well characterized in the development of cervical adenocarcinoma. Twenty-seven paraffin-embedded adenocarcinomas of the cervix, including three cases of adenoma malignum, were analyzed for molecular alterations associated with other gynecologic malignancies. The presence of human papillomavirus (HPV) was assessed by polymerase chain reaction (PCR) using internally nested consensus primers. HPV types were identified by restriction endonuclease digestion of the PCR products, using DNA sequencing to confirm each digestion pattern. The presence of HPV was correlated with immunohistochemical expression of the p53 gene product, the presence of mutations in codon 12 of Ki-ras, and allelic deletion of markers associated with the development of other gynecologic carcinomas. HPV was identified in 16 (59%) of 27 cases, including type 18 in 7 tumors, type 16 in 7 tumors, and type 45 in 2 tumors. HPV types 16 and 45 were always identified in adjacent uninvolved cervical epithelium, but HPV type 18 was absent from the adjacent non-neoplastic epithelium in four of the seven positive cases. HPV was not identified in any of three cases of adenoma malignum. Diffuse immunohistochemical staining of the p53 gene product was present in only one (HPV-negative) tumor. A mutation in codon 12 of Ki-ras was observed in one endocervical adenocarcinoma (with an endometrioid pattern). Loss of heterozygosity was identified only for a marker on chromosome 6p in one mucinous endocervical carcinoma. Most endocervical adenocarcinomas lack molecular alterations characteristic of other histologically similar gynecologic malignancies, as well as those described in cervical squamous cell carcinomas.
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PMID:Analysis of human papillomavirus infection and molecular alterations in adenocarcinoma of the cervix. 1061 75

It was recently reported that cervical adenocarcinoma showed an abnormal expression of estrogen receptor (ER) and cell cycle-related molecules (cyclin E, p53, p16, p21, and p27). To investigate whether similar alterations exist in glandular intraepithelial lesions, the expression of ER, progesterone receptor (PR), Ki-67, and the above cell cycle-related molecules was examined in 15 cases of glandular dysplasia (GD) and 10 cases of adenocarcinoma in situ (AIS), using the immunohistochemical technique. An expression of ER and PR was often decreased or missing in GD and, especially, in AIS. The Ki-67 labeling index was significantly higher in AIS than in GD or normal glandular cells. In GD, expression of all the cell cycle-related molecules was not recognized (except for a few p27-positive cases), a situation comparable to normal glands. In contrast, an abnormal expression of all the cell cycle-related molecules examined was demonstrated in AIS. There was a significant positive correlation, in terms of the extent of staining, between cyclin E and p21 in AIS. These results suggest that an altered expression of these molecules occurs in AIS as it does in invasive adenocarcinoma, and provide additional evidence supporting AIS as a precursor of cervical adenocarcinoma.
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PMID:Abnormal expression of sex steroid receptors and cell cycle-related molecules in adenocarcinoma in situ of the uterine cervix. 1020 66

Twenty-one cases of vulvar Paget's disease were studied to assess possible prognostic indicators, including presence and depth of invasion, status of resection margins, tumor DNA cell content, and immunoreactivity for p53 and estrogen receptor proteins. Immunostaining for cytokeratin 7 (CK7), cytokeratin 20 (CK20), and gross cystic disease fluid protein-15 (GCDFP) were also performed. Patients were 45 to 82 years of age (mean, 66.9 years). Ten of 21 patients (47.6%) had invasive Paget's disease. Dermal invasion was < or = 1 mm in 7 of 10 cases and 2 mm, 3 mm, and 8 mm in the remaining three invasive tumors. Of the seven patients with minimally invasive Paget's disease (< or = 1 mm depth of invasion), five are alive with no evidence of disease, one died of an unrelated illness, and one is alive with biopsy-proven in situ Paget's disease, having refused operative treatment. Of the three patients with more than minimally invasive Paget's disease (> 1 mm), all had nodal metastases; one patient is alive with no evidence of disease, one died of undertermined causes, and one died of metastatic Paget's disease. The remaining 11 patients had Paget's disease confined to the epidermis and its adnexal structures. Seven of these patients were alive at last follow-up with no evidence of disease. Of the remaining four patients, one died of metastatic cervical cancer, one died of metastatic bladder cancer, one died of an unrelated illness, and one patient is alive with biopsy-proven in situ Paget's disease and awaiting operative treatment. Twenty of the 21 cases represented primary vulvar Paget's disease while one represented possible local spread from a cervical adenocarcinoma. The immunoprofiles were GCDFP+/CK7+/CK20- in 14 cases, GCDFP+/CK7+/CK20+ in 4 cases, and GCDFP-/CK7+/CK20- in 2 cases. All tumors were estrogen receptor-negative. Immunostaining for p53 was positive in 16 tumors and negative in four tumors. Seven of 12 (58%) patients with positive margins experienced local recurrence of Paget's disease, while the disease recurred in 1 of 4 patients with negative margins. Recurrence was observed in 3 of 5 patients with diploid tumors and in 4 of 10 patients with aneuploid tumors. Neither of these differences is statistically significant. This study supports the recognition of a category of minimally invasive vulvar Paget's disease that has a low risk of distant metastasis and death caused by disease. Status of surgical resection margins, tumor cell DNA ploidy, estrogen receptor expression, and p53 immunoreactivity are not predictive of local recurrence.
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PMID:Prognostic factors in Paget's disease of the vulva: a study of 21 cases. 1054 44

Using PCR amplification followed by confirmation with BstU I restriction enzyme digestion, the p53 Pro sequence was determined in tissues from 88 normal cervices, in 184 cervical swabs with mildly abnormal Pap smear, in 50 squamous cell cervical carcinoma specimens, and in 30 cervical adenocarcinoma samples. The frequencies for homozygous proline (Pro-72), homozygous arginine (Arg-72), and heterozygous proline/arginine (Pro/Arg-72) were 23% (n = 20), 28% (n = 25), and 49% (n = 43), respectively, in normal cervices; 24% (n = 45), 28% (n = 51), and 48% (n = 88), respectively, in samples with mild dyskaryotic changes in Pap smears; 26% (n = 13), 28% (n = 14), and 46% (n = 23), respectively, in squamous cell carcinomas, and 33.3% (n = 26), 46.2% (n = 36), and 20.5% (n = 16), respectively, in adenocarcinomas. In the present study, we have found that p53 polymorphism may have a role in the development of adenocarcinoma but not squamous cell carcinoma. The arginine-encoding allele may thus be an important factor affecting host susceptibility to the development of adenocarcinoma.
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PMID:Effect of p53 polymorphism on the susceptibility of cervical cancer. 1130 9

Infection with the human papillomavirus is an important co-factor in the development of cervical carcinomas. Accordingly, HPV DNA is recognised in most of these tumours. Polymorphism of the p53 gene, codon 72, is also considered a risk factor in the development of cervical carcinoma. However, this finding is contradicted by several observers. In the present investigation, 111 cases of adenocarcinoma of the cervix collected through the Swedish Cancer Registry and 188 controls (females with normal cytology at organised gynaecological screening) were analysed with regard to p53, codon 72, polymorphism using a PCR- and SSCP-based technique. In the controls, 9% showed pro/pro, 44% pro/arg and 47% arg/arg, whereas in the invasive adenocarcinomas, the corresponding figures were 0%, 29% and 71%, respectively. The difference was statistically significant (P = 0.001). HPV DNA was identified in 86 tumours (HPV 18 in 48, HPV 16 in 31 and HPV of unknown type in 7 cases) and 25 tumours were HPV negative. The p53, codon 72, genotypes observed in HPV-positive and HPV-negative cervical adenocarcinomas were not statistically different (P = 0.690). The results indicate that women homozygotic for arg/arg in codon 72 of the p53 gene are at an increased risk for the development of cervical adenocarcinomas. However, this genetic disposition seems to be unrelated to the HPV infection.
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PMID:The significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas. 1171 Aug 28


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