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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferative rate is an important prognostic marker in breast carcinoma. However, the best measurement method has not been established. This study evaluated mitotic figure counts (MFC) as mitoses per 10 high power fields (HPF) and per 1,000 cells, S-phase fraction by flow cytometry, and Ki-67, MIB-1, and proliferating cell nuclear antigen (PCNA) positivity by immunohistochemistry in 135 breast carcinomas. There was strong correlation between the two MFC methods and significant correlation between MIB-1 positivity and all proliferation markers except Ki-67. S-phase fraction showed significant correlation with all proliferation markers except PCNA. Ki-67 positivity correlated only with S-phase fraction, and PCNA positivity only with MIB-1 and mitoses per 10 HPF. High MFC was associated with other prognostic factors: high histologic tumor grade, absence of biochemical and immunohistochemical hormone receptors, and DNA aneuploidy, but not lymph node involvement or tumor size. MIB-1 positivity was also associated with these parameters, except lymph node involvement, tumor size, and DNA aneuploidy. Mitotic figure count and MIB-1 positivity were associated strongly with disease-free survival, up to 46 months. The other proliferation markers were associated with fewer prognostic factors and showed weak or absent association with disease-free survival. The best proliferation markers are mitotic figure counting (either method) or MIB-1 positivity.
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PMID:Proliferation markers in breast carcinoma. Mitotic figure count, S-phase fraction, proliferating cell nuclear antigen, Ki-67 and MIB-1. 761 Nov 79

Although the Breslow measurement of tumor thickness of melanoma is the most significant predictor of survival, the biologic behavior of thick lesions remains unpredictable. MIB-1, a monoclonal antibody to a Ki-67 epitope, recognizes all proliferating cells. Unlike Ki-67 antibody, which requires frozen tissue, MIB-1 can be used on formalin-fixed tissue. Proliferation, measured by MIB-1 expression and mitotic index, was assessed as a prognostic factor in a group of patients with clinical stage I thick cutaneous melanoma (tumor thickness 4 mm or greater), for which predicted survival is low. From a melanoma data base, 97 patients with this type of melanoma were identified. Of these, 64 had lesional tissue available for study. The median follow-up time was 3.8 years (range 0.42-13.6 years). The percentage of MIB-1 reactivity was scored as low at less than 10% (n = 33), intermediate at 10% to 20% (n = 17), and high at greater than 20% (n = 14). Melanomas with high MIB-1 reactivity were associated with significantly poorer cause-specific survival compared with tumors with intermediate (p < 0.0001) or low MIB-1 reactivity (p = 0.0025). Multivariate analysis demonstrated that MIB-1 reactivity was a significant independent prognostic factor related to cause-specific survival (p = 0.0002) and was more sensitive than tumor thickness or mitotic index in this select group of high-risk patients. Identification of individuals with stage I thick cutaneous melanoma who are at risk of recurrent disease may improve patient management as new therapeutic modalities become available.
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PMID:MIB-1 proliferative activity is a significant prognostic factor in primary thick cutaneous melanomas. 761 70

The composition of collagen was analyzed and the degree of lysyl hydroxylation of individual collagen chains was determined in four osteosarcomas and two osteofibrous dysplasias. In addition, the tumor proliferation (number of mitoses, proliferating-nuclear-antigen-positive cells, MIB) as well as the response to chemotherapy (morphological regression grade) were checked. All tumors contained a high proportion of collagen III and, in all but one osteosarcoma, pepsin-extracted collagens I and III were overmodified. Furthermore, the proportion of diglycosides in collagen I was about four times higher than in controls. The collagen composition and modification resembled those of bones at early stages of human development. One osteosarcoma and both osteofibrous dysplasias were in the normal range of lysyl hydroxylation. There was no correlation between the collagen properties and the histopathological marker of tumor proliferation.
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PMID:Composition and posttranslational modification of individual collagen chains from osteosarcomas and osteofibrous dysplasias. 763 71

We report 25 cases of a peculiar sclerosing epithelioid variant of fibrosarcoma (SEF) simulating an infiltrating carcinoma. The tumors occurred primarily in the deep musculature and were frequently associated with the adjacent fascia or periosteum. The patients' ages were 14 to 87 years (median, 45). Fourteen were male and 11 female. The tumors were located in the lower extremities and limb girdles (12 cases), trunk (9), upper limb girdles (2), and neck (2). They measured 2 to 14.5 cm in greatest dimension (median size, 7 cm) and were gray to white and firm. Histologically, the lesions were characterized by a proliferation of rather uniform, small, slightly angulated, round to ovoid epithelioid cells with sparse, often clear cytoplasm arranged in distinct nests and cords. In all cases there was prominent hyaline sclerosis, sometimes reminiscent of osteoid or cartilage and foci of conventional fibrosarcoma. Occasional myxoid zones with cyst formation and foci of hyaline cartilage, calcification, and metaplastic bone were also seen. Mitotic figures were generally scarce. Vimentin was detected in 13 of 14 cases, epithelial membrane antigen in seven, S100 protein in four, and neuron-specific enolase in two. Cytokeratins were detected with AE1/AE3 and CAM 5.2 in two cases. Leukocyte common antigen, CD68 antigen, HMB45, desmin, and alpha-smooth muscle actin were negative in all cases. In 13 of 14 cases, 75% or more of the cells stained for proliferating cell nuclear antigen (PCNA). Ki67 immunostaining with MIB 1 showed low proliferative activity in all cases, averaging 5% of tumor cells or less. In all cases, p53 was detected by immunohistochemical methods; bcl-2, an antiapoptosis marker, was detected in more than 90% of the cells in 11 of 12 cases. Ultrastructurally, both the epithelioid and spindled tumor cells had features of fibroblasts. Follow-up in 16 cases ranging from 13 months to 17 years 3 months (median, 11 years 4 months) revealed persistent disease or local recurrences in 53% of patients and metastases in 43%. The metastases were to the lungs (4 cases), skeleton (3), chest wall/pleura (3), pericardium (1), and brain (1). Four patients died of disease, four were alive with disease, two were known to be alive but disease status unknown, and six had no evidence of further disease at last follow-up. The data suggest that SEF is a relatively low-grade fibrosarcoma; yet it is fully malignant despite the presence of histologically benign-appearing foci. The proliferation markers PCNA and Ki67 did not correlate with prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sclerosing epithelioid fibrosarcoma. A variant of fibrosarcoma simulating carcinoma. 766 Dec 86

Alterations in the function of p53, a tumor suppressor gene, have been postulated as a principal underlying mechanism involved in the loss of cell cycle control in human malignancies. Because p53 dysfunction is generally associated with protein overexpression, immunocytochemistry is a valuable technique for the analysis of p53's functional status. We tested the hypothesis that loss of p53 function is a critical event in the early development and progression of human malignant melanoma and can lead to alterations in cell proliferation. We performed an immunocytochemical study in archival fixed, embedded specimens that included 102 melanocytic lesions ranging from benign nevi to metastatic melanoma. In addition to p53, we assessed the p53-associated protein, mdm-2, and markers of cell cycle status (the MIB-1-defined cell proliferation marker; proliferating cell nuclear antigen; and statin, a 57-kDa nuclear protein expressed preferentially by G0 cells). Tumor expression of all nuclear proteins was scored in a semiquantitative fashion related to the fraction of positive tumor nuclei. The overall incidence of significant p53 overexpression was low (8% of primary and 14% of metastatic melanomas). Analysis demonstrated strong correlation between increasing p53 expression in primary versus metastatic lesions (chi 2 analysis, P = 0.001). Correlation was found between increased MIB-1-defined cell proliferation and p53 overexpression in primary melanomas (P = 0.02). Detectable mdm-2 expression was significantly correlated with p53 overexpression (P = 0.02). Comparison of statin and proliferating cell nuclear antigen indices demonstrated inverse correlation (chi 2 , P = 0.03) in the combined groups, but within the metastatic group there was a subset of cases strongly expressing the two markers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:p53 and mdm-2 expression in malignant melanoma: an immunocytochemical study of expression of p53, mdm-2, and markers of cell proliferation in primary versus metastatic tumors. 767 73

Mutations of the p53 gene often result in the overexpression of p53 protein. Previous studies have suggested that the function of p53 and its mutant protein forms may be linked with the disease course of patients with a breast carcinoma. In the present study, we tested 462 primary breast carcinomas for the presence of p53 antigen using immunohistochemical methods employing antibodies against the clone, DO-1. These tumors were also immunohistochemically stained using the monoclonal antibody, MIB-1, in order to demonstrate the presence of Ki67. Comparison of the presence of p53 with other prognostic parameters revealed highly significant negative correlations with estrogen- and progesterone-receptor status (P < 0.001 and P = 0.001, respectively) as well as positive correlations with both the presence of MIB-1 (P < 0.001) and the histological grading (P = 0.008). The presence of p53 was not correlated with tumor stage and node status. Evaluation of the findings for all 462 tumors as well as for node-positive and -negative subgroups revealed less favorable findings for overall survival and the disease-free period for both p53-positive tumors (for total group, overall survival, P = 0.0002, disease-free period, P = 0.02; for node-positive group, overall survival, P = 0.0004, disease-free period, P = 0.1045) and breast carcinomas with higher proportions of cell nuclei positive for MIB-1 (total, overall survival, P = 0.0026, disease-free period, P = 0.0022; node-positive, overall survival, P = 0.021, disease-free period, P = 0.0882). We were able to demonstrate that p53 expression in breast carcinomas means a significantly worse prognosis for grade II tumors (overall survival, P = 0.0002; disease-free period, P = 0.0116), for overall survival in the case of estrogen-receptor-positive tumors (P = 0.014), and for tumors showing increased proliferation activity (overall survival, P = 0.0477).
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PMID:Usefulness of immunohistochemical staining for p53 in the prognosis of breast carcinomas: correlations with established prognosis parameters and with the proliferation marker, MIB-1. 770 8

To answer the question why some gastric cancers make elevation while others make depression in their early stage, and why polypoid cancers grow larger than their benign counterpart adenomas, the distribution of proliferating cells and apoptotic cells was compared between these lesions. Proliferating cells and apoptotic cells were detected with anti Ki-67 antibody (MIB-1) and with the in situ nick end labeling (ISNEL), respectively. A total of 62 gastric tumors, taken by the endoscopic mucosal resection method, was assessed. They consisted of 14 adenomas and 48 mucosal carcinomas (27 polypoid and 21 depressed type). Overall positive rates of Ki-67 were 27.5 +/- 9.0% in adenoma, 40.1 +/- 11.1% in polypoid cancer and 47.5 +/- 9.7% in depressed cancer. Proliferating cells were preferentially found in the cripts of metaplastic mucosa, in the middle to upper layer of adenomas, and in the whole layer including their surface of adenocarcinomas. Within cancers the polypoid type had more positive cells in the upper layer, so did the depressed type in the lower layer. ISNEL positive nuclei showed sphere, fragmented, ringed forms, or the same form as neighboring tumor nuclei. Apoptotic cells lay scattered throughout tumor glands. Apoptotic cell counts per 1000 tumor cells were 26.0 +/- 9.7 in adenoma, 36.3 +/- 32.1 in polypoid cancer, and 52.5 +/- 19.3 in depressed cancer. Depressed type cancers and a few polypoid cancers rich in non-tumor tissues showed higher numbers of apoptotic cells than adenomas and usual polypoid cancers. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cell proliferation and cell death (apoptosis) in epithelial tumors of the stomach--analysis of tumor tissues by the endoscopic mucosal resection]. 772 65

Since clear cell meningioma has only recently been recognized as a morphologic entity, its pathobiology has not been studied. Fourteen examples occurring in seven females and six males, ages 9 to 82 years (mean 29 years), were examined; one was associated with type 2 neurofibromatosis. Of these cases, seven (50%) were spinal-intradural (six lumbar, one thoracic), three (21%) arose in the posterior fossa (cerebellopontine angle), three (21%) were supratentorial, and one (7%) was centered upon the foramen magnum. In one case (8%), two tumors were considered to be independent primaries. One tumor (8%) appeared to show no dural attachment. Thirteen tumors were subject to complete study. All were composed of sheets of clear, glycogen-rich, polygonal cells forming only a few vague whorls. Hyalinization, both stromal and perivascular, was often extensive. Mitoses were rare in primary tumors. Immunohistochemistry showed vimentin and epithelial membrane antigen staining to be reactive in 100%. Stains for S-100 protein and CAM 5.2 were negative. Progesterone and estrogen receptor staining was observed in 77% and 0%, respectively. Ultrastructural study showed abundant cytoplasmic glycogen, a few cytoplasmic lumina, intermediate filaments, interdigitation of cell membranes, and desmosomal junctions. The means, medians, and ranges of proliferating cell nuclear antigen (PCNA) and MIB-1 antigen labeling indices for nonrecurring and recurring tumors were 10.4%, 8.8%, 0.8-23.4% and 11%, 1.4%, 0.1-50.3%, as compared with 7.4%, 6.7%, 2.9-17.2% and 13.3%, 13.4%, 3.3-25.7%, respectively. Twelve successful DNA ploidy studies showed that 11 tumors (85%) were diploid and one was tetraploid; percentage S-phase determinations varied from 4 to 9% (mean 6.0%). Recurrence was noted in eight patients (61%) (five of whom had multiple recurrences); there was local discontinuous spread in two cases (15%) and widespread cranial to spinal metastasis in one case (8%). Three patients (23%) are dead of disease. In summary, clear cell meningiomas are morphologically unique, show no sex predilection, affect primarily the lumbar region and cerebellopontine angle, and despite their benign appearance, may be inordinately aggressive, particularly intracranial examples. No close association was noted between recurrence or clinical outcome and such factors as mitotic activity, PCNA proliferation indices, percent S-phase determination, or DNA ploidy status. In contrast, MIB-1 proliferation indices were appreciably higher among recurring tumors.
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PMID:Clear cell meningioma. A clinicopathologic study of a potentially aggressive variant of meningioma. 772 60

We examined whether the determination of cell proliferation and cell death rates was useful in the differential diagnosis between benign and malignant myogenic tumors of gastrointestinal tract. As markers for cell proliferation and cell death, Ki-67 (MIB-1) positive rates or argyrophilic nucleolar organizer region (AgNOR) counts and apoptotic cell counts were determined in a total of 53 myogenic tumors comprising 36 leiomyomas and 17 leiomyosarcomas. Apoptotic cells were detected with the in situ nick end labeling method reported by Gavrieli in 1992 with modifications. Significant differences were observed in the Ki-67 positive rates (leiomyoma 1.8 +/- 1.4%, leiomyosarcoma 8.6 +/- 6.0%, p < 0.0001), in the mean AgNOR counts (leiomyoma 1.77 +/- 0.53, leiomyosarcomas 3.14 +/- 1.02, p < 0.0001), and in the apoptotic cell counts (median; leiomyoma 3.2, leiomyosarcoma 32.5 per 10(6) tumor cells, p < 0.005). All high grade sarcomas were picked up by the Ki-67 index of more than 7%, and almost all leiomyomas were thrown away by the AgNOR counts more than 3.0 within the low Ki-67 cases, which showed 81% of sensitivity and 97% of specificity. These results show that a combination use of Ki-67 and AgNOR is of use in the differential diagnosis between leiomyoma and leiomyosarcoma. Although a significant difference was also noted in apoptotic cell counts between these two categories, this seems not to be a practical index for the discrimination because apoptotic cell death is a rare event in gastrointestinal myogenic tumors.
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PMID:[Cell proliferation and cell death (apoptosis) as indices differentiating malignant from benign gastrointestinal myogenic tumors]. 773 Oct 89

Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid malignancies in infants and represents 7% of all cases of childhood cancer outside of the central nervous system. Thirty-five samples of neuroblastoma from 31 patients were obtained from Duke University Medical Center between 1979 and 1991 and studied to determine the relative prognostic value of a number of clinical, histologic, nuclear, and oncogenic features. The features studied were: stage, Shimada classification, DNA ploidy, MIB-1-proliferation index and status for HER-2/neu, p53 and epidermal growth factor receptor (EGFr). Only age (P = .03), HER-2/neu (P = .01), and p53 (P = .02) reached statistical significance as prognostic indicators. The median survival for patients with HER-2/neu expression was 12 months; median survival for patients with no HER-2/neu expression was 138 months. Similarly, the median survival for patients with p53 expression was 12 months; patients with no p53 expression had a median survival was 144 months. The combination of either HER-2/neu or p53 positivity was especially strong as a prognostic indicator (P = .002).
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PMID:Prognostic indicators for neuroblastoma: stage, grade, DNA ploidy, MIB-1-proliferation index, p53, HER-2/neu and EGFr--a survival study. 774 72


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