Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human papillomavirus (HPV) 16 has previously been found in 19/41 breast carcinomas (46%) in women with a history of HPV 16 positive CIN III lesions. There was no significant difference in distribution of histological subtypes, mean or median tumour diameter or number of regional lymph node metastases in the HPV positive and HPV negative breast carcinoma groups. P53, p21 and c-erbB-2 proteins were analysed by immunohistochemistry in the HPV 16 positive and HPV negative breast carcinomas. There was a significant difference in p53 and p21 protein immunoreactivity between HPV 16 positive and HPV negative breast carcinomas (p = 0.0091 and p = 0.0040), with a significant less detectable p53 and p21 protein immunoreactivity in the HPV 16 positive cases. There was also a significant difference in the coexpression of p53/p21 between the HPV 16 positive and HPV 16 negative breast carcinomas (p = 0.002). No significant difference in immunostaining for c-erbB-2 protein in the two groups was found (p = 0.15), or for the coexpression of p53/c-erbB-2 (p = 0.19). The significantly lower expression of p53 and p21 proteins in HPV 16 positive than in HPV 16 negative breast carcinomas supports the hypothesis of inactivation and degradation of wild-type p53 proteins by HPV 16 E6 and that p53 mutation is not necessary for transformation in the HPV 16 positive cases.
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PMID:Significant difference in p53 and p21 protein immunoreactivity in HPV 16 positive and HPV negative breast carcinomas. 1060 22

Tumour growth is regulated by a balance between proliferation, growth arrest and programmed cell death (apoptosis). Until recently, the majority of the studies dealing with oncogenesis has been focused on the regulation of cell proliferation. There is now growing understanding that control of growth arrest and apoptosis play key roles in the development of human cancer and in cancer treatment. Some of the more heavily studied proteins of importance for the control of growth arrest and apoptosis are p53, p21, bcl-2 and bax. Alterations in the p53 protein may lead to malignant transformation and defect therapy response, most likely as a result of defective p53-dependent apoptosis. In addition, p21 (WAF1/CIP1) is involved in cell-cycle arrest and probably in induction of p53-dependent apoptosis. Proteins belonging to the bcl-2 family are also important for normal apoptosis. Overexpression of bcl-2 protein is thought to reduce the apoptotic capacity, while bax protein seems to be necessary for induction of apoptosis. In this study, we have immunostained tissues from 93 primary colon carcinomas and have examined the expression of p53, p21 (WAF1/CIP1), bcl-2 bax, pRb and cyclin D1 for evaluation of their roles in colon-cancer progression. A highly significant association between p53 accumulation and downregulation of p21 (WAF1/CIP1) was seen. We also found a strong association between reduced/absent p21 and the development of metastases and death due to cancer disease. Cyclin D1, bcl-2 and bax protein failed to have independent prognostic impacts. Bcl-2 and bax protein levels showed an inverse relationship. The results of the present study indicate that reduced p21 protein levels play an important role in progression of colon cancer. We concluded that evaluation of p21 expression in primary colon carcinomas at the time of surgery might be a valuable tool in defining patients with a high risk of developing metastases.
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PMID:Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. 1078 80

Lack of control of metastatic foci is the most prevalent cause of death in patients with oral carcinomas, and it is important for tumor control to identify the factors that predispose patients to death. In the present study, we examined 225 patients with oral squamous cell carcinoma and investigated the immunohistopathological characteristics of 43 tumors that led to death, comparing them with those of the non-lethal tumors. In the 43 patients, lack of control of the primary site, lymph node and distant metastatic tumors were noted in 20, 18 and 16 patients, respectively. The mode of tumor cell invasion was closely correlated with death. The diffuse invasion modes of grades 4C and 4D were observed in 15 (34.9%) of the 43 tumors with a poor outcome and in 35 (19.2%) of the 182 controlled tumors (p < 0.02). The expression of p53 was highly correlated with death. Of the tumors with poor prognosis, p53 protein was expressed in 32 tumors (76.2%). However, p53 protein expression was observed in 52.7% of the tumors with good prognosis (p < 0.02). In contrast, the expression of p21 protein in the well-controlled tumors (30.4%) was almost equal to that of the 43 lethal tumors (26.2%). Compared with the ratios of local recurrence, metastases and their treatment failures in the p53-negative grade 1 and 2 tumors, those in the mutant p53-positive grade 3, 4C and 4D tumors were mostly high. These results indicate that measuring p53 protein expression and evaluating the mode of tumor cell invasion are important for oral carcinoma therapy because the expression of mutant p53 protein and the diffuse modes of tumor cell invasion indicate a predisposition toward a poor prognosis.
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PMID:Diffuse mode of tumor cell invasion and expression of mutant p53 protein but not of p21 protein are correlated with treatment failure in oral carcinomas and their metastatic foci. 1089 65

Recent in situ hybridization experiments have shown a high content of IGF-II mRNA in breast cancer stroma. The aim of this study was to examine the relationship between IGF-II protein expression and several prognostic parameters in 75 infiltrating ductal carcinomas (IDC) of the breast. Tissue sections were evaluated for proliferative activity, IGF-II protein, ER, PgR, p53, and p21 expression using immunohistochemical procedures. The degree of stromal proliferation was assessed. Menopausal status, axillary lymph node involvement and nuclear grade were known. Thirty-five patients (44.3%) were premenopausal and 47 (62.6%) had lymph node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected both in the tumor stroma and in the cytoplasm of epithelial cancer cells: a high IGF-II content was found in 12 specimens (16.0%), a low content in 14 (18.7%) and a moderate content in 31 (41.3%). Twenty-four tumors (32.0%) showed high proliferative activity. Both ER and PgR were expressed in the nucleus of cancer cells: 49 tumors (65.3%) were ER positive (ER+) and 34 (45.3%) PgR positive (PgR+). p21 protein was detected in 37 tumors (49.6%) and p53 in 12 (16%). IGF-II protein was not correlated with menopausal status, lymph node metastases, nuclear grade, proliferative activity, ER or p53. In contrast, IGF-II correlated strongly with stromal proliferation (p=0.008), PgR (p=0.03) and p21 (p=0.01). This study demonstrates that in IDC of the breast IGF-II protein is expressed in the epithelium and stroma of the majority of tumors and is correlated with stromal amount, PgR and p21 expression. These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.
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PMID:Insulin-like growth factor II (IGF-II) immunohistochemistry in breast cancer: relationship with the most important morphological and biochemical prognostic parameters. 1211 87

Papillary thyroid cancer (PTC) is a slow-growing tumor with a favorable outcome. Still, some low-risk patients develop local or distant metastases and eventually die from their disease. Many molecular markers are involved in proliferation and apoptosis, including Bcl-2, Ki-67, and p21. Because age over 45 is the most important determinant of a poor survival, we analyzed whether the expression of these tumor proliferation markers differs between young and older PTC patients. Our study comprised 108 PTC patients retrospectively selected by age, i.e. those younger than 35 or older than 55 at diagnosis. Formalin-fixed, paraffin-embedded archival tissue blocks were analyzed for Bcl-2, Ki-67, and p21 protein expression by immunohistochemistry. We showed that expression of Ki-67 increases significantly with age, indicating that tumors in older patients may grow faster. This higher proliferative activity may explain the worse prognosis in these patients. Expression of p21 was higher in large tumors and in tumors extending beyond the thyroid capsule. Expression of Bcl-2 did not correlate with clinical parameters.
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PMID:Immunohistochemical expression of Bcl-2, Ki-67, and p21 in patients with papillary thyroid cancer. 1575 57


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