Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myxofibrosarcoma, also known as a myxoid variant of malignant fibrous histiocytoma, is one of the most common sarcomas in the extremities of elderly people and is characterized by a high frequency of local recurrence. We report a case of myxofibrosarcoma, intermediate grade, involving the thigh along the fascial plane and between the muscles without the formation of an apparent nodular lesion. On microscopic examination, the tumor lacked areas of necrosis and pronounced cellular pleomorphism, but it was highly cellular with proliferation of spindle cells which contained large elongated, hyperchromatic and irregularly shaped nuclei, slightly eosinophilic cytoplasm and indistinct cell margins, arranged in both interlacing fascicles and a storiform pattern. Immunohistochemically, many of the tumor cells showed intense reactivity to vimentin and CD34. More than 20% of the cells were positive for p53 protein and the MIB-1 labeling index was approximately 30%. Desmin, alpha-smooth muscle actin, muscle-specific actin, S-100 protein, cytokeratin, epithelial membrane antigen, bcl-2 protein and neurofilament were negative. The absence of a discrete mass lesion and diffuse infiltrative nature precluded early recognition of tumor. Seven years after hindquarter amputation, the patient has been alive without evidence of local recurrence or distant metastasis. This case indicates that myxofibrosarcoma can demonstrate a highly infiltrative growth pattern. It is possible that this infiltrative nature is associated with a high rate of local recurrence of the tumor. A careful radiological examination of the extension of the tumor prior to surgery is mandatory considering the infiltrative nature of myxofibrosarcoma.
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PMID:Myxofibrosarcoma with an infiltrative growth pattern: a case report. 1118 94

Paragangliomas of the nasal cavity and paranasal sinuses are extremely rare. This study was conducted to investigate the biologic characteristics of these lesions on different molecular levels and to estimate their biologic behavior. Operative specimens of three patients who underwent surgery for a paraganglioma of the nasal cavity (one case) or paranasal sinuses (two cases) were investigated by routine histology, quantitative DNA analysis, and immunohistochemical assessment of proliferation markers (i.e., Proliferating Cell Nuclear Antigen, PCNA; Ki67-MIB-1), the expression of cell-surface antigens, which reflect the tumor-stroma interaction (i.e., CD 44 v0.4/5 and 6, CD 54, CD 106), oncogene products (nm-23; p53), and bcl-2 as a marker of apoptosis. Histologically, two tumors were paragangliomas of the adenomatous subtype, one lesion was classified as angiomatous. According to DNA analysis, aneuploid cells were detected in all tumors. Two of three paragangliomas were classified as a DNA type III pattern, implying a high percentage of aneuploid cells and an aggressive behavior. Immunohistochemically, paragangliomas of the nasal cavity showed increased scores for both proliferation markers tested, indicating a rapid growth pattern. According to the expression of cell-surface markers and oncogene products, these tumors displayed an aggressive behavior and an infiltrating growth pattern. The highest value for the parameters of quantitative DNA analysis and highest proliferation scores were found in a tumor of a patient who developed multiple tumor recurrences after radical excision of the lesion with clear margins, and finally died of disease. In conclusion, paragangliomas of the nasal cavity and paranasal sinuses examined in this study should be regarded as suspicious concerning their biologic and clinical behavior. Radical excision, and in cases with highly aggressive biology, postoperative radiation therapy are recommended. Tumor biologic examinations can help to recognize high-risk patients for developing recurrences and possibly lesions with a malignant behavior and to enhance our understanding of the biology of these extremely rare tumors of the nasal cavity and paranasal sinuses.
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PMID:Biologic characteristics of paragangliomas of the nasal cavity and paranasal sinuses. 1119 19

Little is known about the renewal of some groups of cells in dental pulp, and the occurrence and significance of physiological cell death in dental pulp is not yet understood. The possibility of odontoblast disappearance by apoptosis has been proposed, and the presence of apoptotic cells in the rat and human odontoblastic and subodontoblastic layers has been recently described. bcl-2 and p53 are proteins involved in the apoptotic pathway, whereas MIB-1 is a proliferating cell marker. The aim of our study was an immunohistochemical evaluation of bcl-2, p53, and MIB-1 in healthy normal pulps of young human subjects. With bcl-2 immunostaining, some positive cells were found in the odontoblastic and subodontoblastic layers, whereas with MIB-1, only a few stromal cells were positive, and all odontoblasts were consistently negative. No cells were positive to p53. The bcl-2 immunoreactivity of the cells of the odontoblastic and subodontoblastic layers could help to explain the presence of apoptotic cells found in these regions.
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PMID:bcl-2, p53, and MIB-1 in human adult dental pulp. 1119 23

Tumor growth is the net result of cell proliferation and cell death. To investigate the relationship between these phenomena in ductal carcinoma in situ (DCIS), we studied proliferation index (PI) in DCIS in relation to the expression of two proteins involved in the regulation of cell death, bcl-2 and p53. Thirty-nine consecutive cases of DCIS were studied. PI was determined using immunolabeling with the monoclonal antibody MIB-1. The proportion of MIB-1-positive nuclei among 500 tumor cell nuclei was determined for each case and constituted the PI. All cases were also assessed immunohistochemically for bcl-2 and p53 protein expression. DCIS cases were graded using the criteria of Holland et al. PI ranged from 0 to 57% (mean 11.2%, median 4.6%). PI was significantly lower in well-differentiated and intermediately differentiated DCIS cases (mean 7.3% and 4.8%, respectively) than in poorly differentiated lesions (mean 24%, p = 0.01). PI was significantly lower in bcl-2-positive cases than in bcl-2-negative cases (mean PI for bcl-2-positive cases 6% and for bcl-2-negative cases 26%, p = 0.01). PI was higher in lesions expressing the p53 protein than in p53 negative cases (19% versus 8.3%), but this difference did not reach statistical significance. PI was also examined in relation to combinations of bcl-2 and p53 expression. Twenty-five of the DCIS lesions (64%) showed the bcl-2-positive/p53-negative phenotype which is similar to that seen in normal breast tissue and benign lesions and can be considered the "physiologic" combination. Among these cases the mean PI was 6.4%. In contrast, 14 cases showed "aberrant" combinations of bcl-2 and p53 expression suggesting dysregulated control of apoptosis. Among these cases the mean PI was 19.6% (p = 0.03). The highest mean PI was in cases with the bcl-2-negative/p53-positive phenotype (PI = 29.7%). DCIS lesions with the physiologic bcl-2-positive/p53-negative phenotype have low PI. In contrast, DCIS lesions with "aberrant" bcl-2/p53 phenotypes have high PI. This combination may favor tumor growth and progression in DCIS.
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PMID:MIB-1 Proliferation Index in Ductal Carcinoma In Situ of the Breast: Relationship to the Expression of the Apoptosis-Regulating Proteins bcl-2 and p53. 1134 99

Nephrogenic rests (NR) are foci of persistent embryonal renal tissue. Because it has been suggested that NRs are precursor lesions to Wilms' tumor (WT), they are of considerable clinical interest. NRs vary from microscopic foci to macroscopic renal tumors, but only a few progress to WT. In this study, patients with NRs detected during the treatment of bilateral WT were compared to a group of patients with NRs incidentally discovered in various clinical settings. Because mechanisms leading to NR growth and WT formation are poorly understood, bcl-2 and MIB expression were studied by immunohistochemistry in both groups. Bcl-2 is an oncoprotein with inhibitory effects on apoptosis and MIB is a well-established marker of cell proliferation. Both mechanisms may be of interest for the growth, regression and transformation of NRs. Intense positive staining for bcl-2 was found in microscopic NRs. Blastemal cells and cells with epithelial differentiation were bcl-2-positive. The same pattern of bcl-2 expression was found in NRs with and without associated WT. High proliferative activity with intense MIB expression was found in blastemal areas of WT. Bcl-2 expression in NR is reported for the first time. Inhibition of apoptosis as a mechanism of NR formation is suggested. This is of special interest, because bcl-2 is under transcriptional control of the WT-1 gene.
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PMID:Expression of MIB and BCL-2 in patients with nephrogenic rests with and without associated Wilms' tumors. 1137 Oct 29

A left atrial tumor, in which radical resection was impossible, demonstrated two processes: An inflammatory pseudotumor and cellular atypia suggestive of a sarcoma. Immunohistochemistry (proliferating cell nuclear antigen [PCNA], MIB-1 [Ki-67 antibody], bcl-2 positive; p53 negative, focal loss of nm23) was supportive for a malignant tumor. Despite no further therapy because of uncertainty in tumor classification, the patient remained in remission for 28 months. Thereafter, spine metastases and local regrowth were found, and the patient died 15 months later, after temporary remission by radiotherapy. This case stresses the impact immunohistochemistry may have on diagnosis of malignancy and the difficulty in predicting the biological behavior of cardiac sarcomas.
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PMID:A primary cardiac sarcoma with unusual histology and clinical course. 1138 22

Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin H synthase, has been implicated in the growth and progression of a variety of human cancers. Although COX-2 overexpression has been observed in human gliomas, the prognostic or clinical relevance of this overexpression has not been investigated to date. In addition, no study has analyzed the relationship between COX-2 expression and other molecular alterations in gliomas. Consequently, we examined COX-2 expression by immunohistochemistry in tumor specimens from 66 patients with low- and high-grade astrocytomas and correlated the percentage of COX-2 expression with patient survival. We also analyzed the relative importance of COX-2 expression in comparison with other clinicopathological features (age and tumor grade) and other molecular alterations commonly found in gliomas (high MIB-1 level, p53 alteration, loss of retinoblastoma (Rb) protein or p16, and high bcl-2 level). Kaplan-Meier analyses demonstrated that high COX-2 expression (>50% of cells stained positive) correlated with poor survival for the study group as a whole (P < 0.0001) and for those with glioblastoma multiforme in particular (P < 0.03). Cox regression analyses demonstrated that COX-2 expression was the strongest predictor of outcome, independent of all other variables. In addition, high COX-2 expression correlated with increasing histological grade but did not correlate with positive p53 immunostaining, bcl-2 expression, loss of p16 or retinoblastoma protein expression, or high MIB-1 expression. These findings indicate that high COX-2 expression in tumor cells is associated with clinically more aggressive gliomas and is a strong predictor of poor survival.
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PMID:Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. 1138 63

We hereby present a retrospective clinicopathological and immunohistochemical study of surgically resected primary gastrointestinal (GI) lymphoma with an analysis of parameters of potential prognostic relevance. From a larger series of 144 cases of primary GI lymphomas, we chose 61 cases with sufficient clinical follow-up (mean 60, range 1-219 months), classified either as extranodal marginal zone B-cell lymphoma of MALT type (MALT lymphoma) or diffuse large B-cell lymphoma (DLBCL), after having excluded other subtypes. In addition to conventional clinical and morphological parameters, the expression levels of Ki-67 (MIB-1), bcl-2 and p53 were evaluated for prognostic significance. Twenty-one (34.4%) cases were classified as pure low grade marginal zone B-cell lymphoma of MALT type, 12 (19.7%) cases as low grade MALT lymphoma with a high grade component (mixed type), and 28 (45.9%) cases as primary extranodal DLBCL. Most of the lymphomas (53/61; 86.9%) were localized in the stomach, 3 (4.9%) in the small bowel, 3 (4.9%) multifocal in both stomach and small intestine and 2 (3.3%) in the large bowel. MIB-1 expression in more than 30% of tumor cells was detected in 42 (68.6%), bcl-2 expression in 20 (32.8%) and p53 accumulation in more than 10% of neoplastic cells in 16 (26.2%) lymphomas. Both high Ki-67 expression and p53 accumulation were more prevalent in the DLBCL. 30 (49%) patients showed lymph node involvement at surgery, 14 (23%) patients suffered tumor recurrence, and 24 (38.5%) died during the follow-up period. Tumor recurrence occurred primarily in patients who had presented lymph node involvement (9/14, 64.3%). The 5-year survival rate was 66.1% for all patients. Important prognostic factors for overall survival were tumor stage (p < .004) and p53 accumulation (p < .05) in univariate analysis, and tumor stage in multivariate analysis (p < .001). Although p53 accumulation did not reach statistical significance in our small study group, it may be both important in the transformation of low grade MALT lymphoma and an indicator for aggressive behavior in high grade tumors.
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PMID:Primary gastrointestinal B-cell lymphoma. A clincopathological and immunohistochemical study of 61 cases with an evaluation of prognostic parameters. 1143 65

We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer.
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PMID:Longstanding survival without cancer progression in a patient affected by endometrial carcinoma treated primarily with leuprolide. 1148 60

In spite of the benign nature of subependymal giant cell astrocytomas (SEGAs), some show massive hemorrhage, rapid growth, and tumor recurrence. This led us to investigate the biological behavior, cell dynamics, and tumorigenesis of SEGAs. All patients (4 men and 3 women; age range, 6-27 years; mean, 13.6 years) had features of tuberous sclerosis complex and obstructive hydrocephalus. One patient had intratumoral bleeding. In two patients, sequential neuroimaging showed a subependymal nodule growing to become a SEGA. All underwent surgical resection without radiation therapy. One tumor recurred and was treated surgically. There were no postoperative deaths. The presence of cytologic atypia, mitoses and vascular proliferation had no implication in terms of the clinical course. MIB-1 labeling indices were low (mean, 0.9), indicating low proliferative potential. Unexpectedly, bcl-2 staining was sparse and bax staining predominated in majority of cases. However, the mean value of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling index was low. Immunohistochemically, tumors were positive for both glial and neuronal markers. In the majority of our cases, the expression of p53 was low. Only one tumor was focally positive for tuberin. SEGAs have low proliferative potential and apoptotic activity, and exhibit features of mixed glial-neuronal differentiation. In contrast to p53, tuberin is suggested to be the tumor suppressor in this tumor.
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PMID:Biological behavior and tumorigenesis of subependymal giant cell astrocytomas. 1151 51


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