Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sporadic adenomas are said to exhibit an orderly growth pattern with a reversal of proliferative and apoptotic cell distribution as compared with normal colonic crypts. Dysplastic polyps of patients with ulcerative colitis (UC) may represent dysplasia-associated lesions or masses (DALM) with a high associated cancer risk, or, alternatively, may represent sporadic adenomas. Histologic criteria to differentiate between sporadic adenomas and DALM have not focused on the balance between cell renewal and cell loss. The expression of the novel anti-apoptosis gene product, survivin, and the proliferation markers, Ki-67 and Y-box binding protein (YB-1), were investigated by immunohistochemical localization in sporadic adenomas and DALM lesions of patients with UC. In adenomas, KI-67 was expressed preponderantly at the luminal aspect of the polyp, whereas its expression was diffuse in DALM. Survivin was detected diffusely in both adenomas and DALM. YB-1 showed positive staining in the deep aspect of adenomatous glands but only to a minor degree at the surface, whereas both deep and diffuse expression patterns of YB-1 were seen in DALM. The authors conclude that DALM and sporadic adenomas exhibit different patterns of cellular proliferation and that molecular markers of cell proliferation, Ki-67 and YB-1, may be useful to distinguish sporadic adenomas from DALM. However, the similar expression of survivin suggests that the underlying mechanisms that regulate apoptotic cell death are uniform in these lesions.
Appl Immunohistochem Mol Morphol 2001 Jun
PMID:Expression of survivin, YB-1, and KI-67 in sporadic adenomas and dysplasia-associated lesions or masses in ulcerative colitis. 1139 32

To determine if carcinogenic events in vulvar skin precede the onset of morphologic atypia, the authors investigated for derangements in DNA content, cell proliferation, and cell death in vulvar carcinomas and surrounding skin in 140 samples of tumor and surrounding skin collected from 35 consecutive vulvectomy specimen for squamous cell carcinoma (SCC) or vulvar intraepithelial neoplasia (VIN) 3. Vulvar non-cancer excisions were used as controls. Investigations consisted of histologic classification and measurement of 9 variables--epidermal thickness (acanthosis and rete ridge length), immunolabeling index (LI) for 3 proteins (p53 protein, Ki-67, and mdm-2), pattern of p53 expression (dispersed vs. compact), DNA content index, and presence of aneuploidy by image analysis and apoptotic rate by Apotag labeling. Significant positive correlations were found for all nine variables studied versus increasing histologic severity in two proposed histologic stepwise models of vulvar carcinogenesis (lichen sclerosus (LS) and VIN 3 undifferentiated associated SCC groups). High p53 LI (>25) and the compact pattern of p53 expression (suspected oncoprotein) significantly correlated with LS and its associated vulvar samples compared with samples not associated with LS (P < or = 0.001). Furthermore, p53 LI, mdm-2 LI, and pattern of p53 expression were concordant between patient matched samples of LS and SCC. In addition, mdm-2 LI significantly correlated with dispersed pattern p53 LI suggesting a response to wild-type p53 protein accumulation. These findings support the hypothesis that neoplastic transformation occurs in sequential steps and compromises proteins involved in the cell cycle control. Concordance of p53 and mdm-2 protein expression in LS and adjacent SCC provides evidence that LS can act as a precursor lesion in the absence of morphologic atypia. Overexpression of mdm-2 with stabilization and inactivation of p53 protein may provide an alternate pathway for vulvar carcinogenesis.
Appl Immunohistochem Mol Morphol 2001 Jun
PMID:Concordant p53 and mdm-2 protein expression in vulvar squamous cell carcinoma and adjacent lichen sclerosus. 1139 33

The significance of p53, a prominent tumor suppressor gene, and its product in various neoplasms including pancreatic adenocarcinoma has been established. We investigated the expression of two types of homologue of p53, p73 and p63, in pancreatic adenocarcinoma by means of immunohistochemistry. Overexpression of p73 was observed in 45.6% of the cases and this phenomenon was more frequently seen in cystic adenocarcinomas than in ductal carcinomas. Furthermore, p73 overexpression was inversely linked to lymph node metastasis, tumor size, and Ki-67 labeling index. On the other hand, p63 overexpression was observed in 68.2% of the cases, but was not related to any clinicopathological features. No correlation was established between the expression of these proteins and aberrant p53 expression. These results suggest that decreased expression of p73 protein and over-expression of p63 protein may play a role in the development of pancreatic adenocarcinoma.
Int J Mol Med 2001 Jul
PMID:Expression of p73 and p63 proteins in pancreatic adenocarcinoma: p73 overexpression is inversely correlated with biological aggressiveness. 1140 52

Amplification of int-2/FGF-3 gene was investigated by differential polymerase chain reaction (dPCR) in 440 archival primary breast carcinoma tissues. Of these, 23 were comedo ductal carcinoma in situ (DCIS), 18 were non-comedo DCIS, 41 were comedo DCIS with adjacent invasive ductal carcinomas, 19 were non-comedo DCIS with adjacent invasive ductal carcinomas, 270 were invasive ductal carcinomas, 33 were invasive lobular carcinomas, 21 were colloid carcinomas and 15 were medullary carcinomas. Int-2 was amplified in 22% (96/440) of the primary breast carcinomas. It was shown that int-2 was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 29% (12/41) of the adjacent invasive ductal carcinomas, 26% (71/270) of the invasive ductal carcinomas, 18% (6/33) of the invasive lobular carcinomas, 10% (2/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. In contrast, int-2 was not amplified in non-comedo DCIS and invasive ductal carcinomas with adjacent non-comedo DCIS lesions. A significant association was observed between int-2 amplification in the in situ components and adjacent invasive lesion (P<0.05). All tumors with int-2 amplification in the in situ lesions (7/7) also demonstrated same degree of amplification in the adjacent invasive components. However, 9% (5/53) of the tumors with no amplified int-2 gene in the in situ components showed int-2 amplification in the adjacent invasive lesions. A significant relationship was noted between amplification of int-2 and lymph node metastases (P<0.05) and poorly differentiated tumors (P<0.05) but not with estrogen receptor status (P>0.05) and proliferation index (Ki-67 and PCNA) (P>0.05). In Malaysia, majority of the patients belong to younger age group (<50 years old) but a comparison of the age groups showed that the amplification of int-2 was not statistically associated with patient age (P>0.05). These observations indicate that amplification of int-2 tends to strengthen the view that int-2 may have the potential to be an indicator of poor prognosis regardless of the age of the patient. Moreover, the presence of int-2 amplification in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that int-2 could be a marker of genetic instability occurring in early and late stages of tumor development.
Int J Mol Med 2001 Aug
PMID:Detection of amplified int-2/FGF-3 gene in primary breast carcinomas using differential polymerase chain reaction. 1144 74

The expression of two novel proliferation-associated markers, mitosin and topoisomerase IIalpha (Topo IIalpha), was evaluated immunohistochemically in consecutive paraffin sections from 60 diffuse astrocytomas (grades 2 to 4) in relation to clinicopathologic parameters, proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1) expression and survival. The percentage of mitosin and Topo IIalpha-positive cells (LI) increased with grade and Ki-67 LI, but could not discriminate between grade 3 on the one hand and grades 2 or 4 on the other hand. In 51% of cases, Ki-67 LI exceeded Topo IIalpha LI, especially within grade 4. Topo IIalpha and mitosin expression was adversely related to overall and disease-free survival in the entire cohort and in grades 2/3. However, only Topo IIalpha LI affected disease-free survival in grade 4 tumors. Multivariate analysis selected only mitosin LI along with the age of the patient, as the independent parameters predicting overall survival, whereas Topo IIalpha emerged as the single independent predictor of disease-free survival. It is concluded that the proliferative potential of astrocytomas, as measured by mitosin and Topo IIalpha immunostaining, conveys useful prognostic information, in addition to that obtained by standard clinicopathologic parameters.
Appl Immunohistochem Mol Morphol 2001 Sep
PMID:Mitosin and DNA topoisomerase IIalpha: two novel proliferation markers in the prognostication of diffuse astrocytoma patient survival. 1155 47

Advanced maternal age is known to be a risk factor for various kinds of obstetric complications, including placental dysfunction. As a first step towards determining the maternal age-related changes in placental, as well as trophoblastic function, we examined the incidences of apoptotic and proliferative cells in trophoblasts of placentae from women of various ages using the TUNEL method and immunohistochemistry for Ki-67 antigen. Tissue sections were collected from the placentae of healthy mothers with normal delivery of healthy babies so that the placental cell kinetics maintaining normal pregnancy and delivery could be studied. The TUNEL-positive cells of the placenta were syncytiotrophoblasts with clustering of nuclei and the TUNEL-positive index of these cells varied from 0.28-1.2%. This index revealed a significant inverse correlation with maternal age. In contrast, the Ki-67-positive index of mononuclear trophoblasts of the placenta ranged between 1.2-2.8% and showed a positive correlation with maternal age. Many of the apoptotic cells of placental villi expressed the pro-apoptotic Bak protein, but were negative for expression of the anti-apoptotic Bcl-2 protein. These results suggest that trophoblasts have higher proliferative activity in older mothers, with a normal process of pregnancy and delivery. The Bcl-2 family proteins could be important for the regulation of trophoblastic apoptosis, although the cellular and molecular mechanisms mediating maternal age-related changes of the placenta remain to be determined.
Mol Hum Reprod 2001 Dec
PMID:Effect of maternal age on incidences of apoptotic and proliferative cells in trophoblasts of full-term human placenta. 1171 96

The nm23 gene was originally identified by differential hybridization of metastatic murine melanoma cell lines. Some experimental studies demonstrated a significantly reduced metastatic potential of melanoma cell lines transfected with the nm23 gene. In this study, we clarified the relationship between lymph node status and nm23 immunoreactivity, as well as Ki-67 labeling index (LI), of human breast cancer. Of the 44 breast invasive ductal carcinomas, nm23-diffusely positive expression [nm23(+)] was detected in 17 (38.6%), and focally positive/negative expression [nm23(+/-/-)] in 27 (61.4%) cases. Lymph node metastasis was found at a significantly higher incidence in the nm23(+/-/-) cases (18/27, 66.7%) than in the nm23(+) cases (4/17, 23.5%) (p>0.001). In the lymph node metastasis-positive cases, mean LI of Ki-67 cells was 20.9% at the center of the tumors and 24.0% at the advanced margins. In the lymph node metastasis-negative cases, mean LI of Ki-67 cells was 12.4% at the center of the tumors and 27.2% at the advanced margins. Decrease of nm23 expression, but not Ki-67 LI, was significantly correlated with lymph node metastasis of breast invasive ductal carcinoma.
Int J Mol Med 2002 Jan
PMID:Decreased nm23 expression, but not Ki-67 labeling index, is significantly correlated with lymph node metastasis of breast invasive ductal carcinoma. 1174 91

Retinoids are a group of compounds which inhibit cell proliferation and induce cellular differentiation. The aim of this study was to compare the antiproliferative activity of various concentrations of 13-cis retinoic acid (isotretinoin) and all-trans retinoic acid (tretinoin) in a culture of the estrogen-sensitive human breast cancer cell line MCF-7. Evaluation was based on [3H]thymidine incorporation into the cancer cells and through immunocytochemical analysis of cell cycle-associated PCNA and Ki-67 protein expression. Both retinoids inhibited [3H]thymidine incorporation into the cancer cells most effectively at a concentration of 3x10(-3) M. Two basic substances used for line MCF-7 culture experiments, one stimulating - estradiol - and the other inhibiting - tamoxifen - were applied. Estradiol added to a culture containing decreasing concentrations of isotretinoin (from 3x10(-3) to 3x10(-8) M) caused a statistically significant reduction in the percentage of [3H]thymidine incorporation into the cancer cell line MCF-7, compared to the 17 beta estradiol group (189.25%+/-62.64, control=100%, p<0.05). In the group of decreasing tretinoin concentrations, statistically significant differences were found only at 3x10(-3), 3x10(-4) and 3x10(-8) M. Following culture supplementation with tamoxifen (1 microM), statistically significant differences were observed only at the highest concentrations of both retinoids (3x10(-3) and 3x10(-4) M). The evaluation of breast carcinoma cells with a positive immunocytochemical reaction to PCNA and Ki-67 has revealed that isotretinoin reduces their percentage in the most determined and statistically significant way (38.00%+/-2.58 and 39.25%+/-3.09), compared to the control group (86.50%+/-9.20 and 100%+/-3.87, p<0.001 and p<0.0001) and to the estradiol group (87.00%+/-6.79 and 86.10%+/-7.0, p<0.001). Apart from their blocking effect on the cell cycle, retinoids also induce the apoptotic pathway.
Cell Mol Biol Lett 2001
PMID:13-cis retinoic acid and all-trans retinoic acid in the regulation of the proliferation and survival of human breast cancer cell line MCF-7. 1175 38

Malignant fibrous histiocytoma (MFH) represents a heterogeneous soft tissue sarcoma entity. The authors compared different methods to determine immunohistochemical staining in whole tissue sections, evaluated the tissue microarray technique, and assessed immunohistochemical heterogeneity using the proliferation marker Ki-67 in 47 histopathologic tumor blocks from 11 MFHs. Whole tissue sections were assessed counting 400 cells along a line and counting all cells in 10 high-power fields (0.16 mm2) with mean Ki-67 expression levels of 13% and 11%, respectively. For the tissue microarray technique, two to three 0.6-mm diameter biopsies were studied from each of the 47 tumor blocks. Good correlation was obtained between whole tissue immunohistochemistry and tissue microarray with the microarray method, giving on average 8.6% greater Ki-67 expression levels than the reference method. Immunohistochemical tumor heterogeneity, evaluated using the high-power field method, showed a median standard deviation of 2.3% within the tumor blocks and 2.5% between the blocks from the same tumor. The authors concluded that the tissue microarray technique yields good quality staining and expression levels for Ki-67 comparable with whole tissue methods in MFH, but because of tumor heterogeneity, several tumor blocks ideally should be studied and, because of loss of material in the microarray process, multiple biopsies should be taken. The feasibility of tissue microarray for immunohistochemical studies of soft tissue sarcomas offers new possibilities to study multiple markers in large tumor materials.
Appl Immunohistochem Mol Morphol 2001 Dec
PMID:Tissue microarray technique in soft tissue sarcoma: immunohistochemical Ki-67 expression in malignant fibrous histiocytoma. 1175 64

Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer.
Int J Mol Med 2002 Feb
PMID:Protein expression and molecular analysis of c-myc gene in primary breast carcinomas using immunohistochemistry and differential polymerase chain reaction. 1178 32


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