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

Bone tumors represent a group of tumors of various dignity. In spite of this single tumor entities may display strong morphological resemblance to each other which can in turn result in profound difficulties in differential diagnosis. The biological behaviour of a tumor is mainly determined by its rate of proliferation. In this study the rate of proliferation of 64 bone tumors (30 high-grade central osteosarcomas, 6 low-grade osteosarcomas, 8 giant cell tumors, 8 aneurysmatic bone cysts, 5 osteoidosteomas/osteoblastomas, 7 fibrous dysplasias and 5 cases of a myositis ossificans) were analysed. Immunohistochemistry was performed on paraffin-embedded tissue sections using the MIB-1 monoclonal antibody. MIB-1 recognizes the proliferation-associated Ki-67 protein which is expressed during the active phases of the cell cycle but cannot be detected in senescent cells. Among high-grade central osteosarcomas a significantly higher rate of proliferation (average value 30%) was found in comparison with low-grade osteosarcomas and other benign intraosseous bone tumors. This approach proved to be very useful in the distinction between high-grade and low-grade osteosarcomas as well as bone-forming intraosseous tumors. However distinguishing low-grade osteosarcomas from benign bone tumors by determining only the rate of proliferation was not possible, although interestingly, the proliferative rate of myositis ossificans, a purely reactive lesion, was in the range of the values determined for high-grade osteosarcoma.
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PMID:[Cell proliferation in bone tumors. Immunohistologic study of Ki-67 protein expression]. 868 97

Both nuclear morphometry and an evaluation of the cell proliferative activity have been reported to be useful tools in predicting prognosis in malignant tumors. There have been few reports, however, on rhabdomyosarcoma regarding these evaluative techniques. We performed nuclear morphometry on 51 tumor specimens obtained either by biopsy or by resection of primary and untreated rhabdomyosarcomas, and we then evaluated MIB-1 staining on 25 of the 51 specimens. The morphometric analysis was semiautomatically performed on hematoxylin- and eosin-stained sections by using a personal computer. The areas, perimeters, and lengths of the major and minor axes of the best fitting ellipse of the nuclei were all measured. In addition, the Form Ell (nuclear ellipsoidity score: minor axis/major axis) was calculated. Using the monoclonal MIB-1 antibody, which detects Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, immunohistochemical studies were performed. The values of the major and minor axes and the Form Ell showed significant differences between each histologic subtype whereas the values of nuclear areas did not. We defined the nucleus whose Form ELL was smaller than 0.25 as spindle-shaped nuclei and then divided all cases into two groups on the basis of the ratio of the spindle-shaped nuclei to the total number of nuclei of the tumor cells. The group with the higher ratio showed a significantly better prognosis (P < 0.05). The same trends were also found in the specimens with an embryonal subtype. Nuclear morphometry was a useful tool in predicting prognosis. In particular, the appearance of spindle tumor cells in rhabdomyosarcoma correlated with a better prognosis.
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PMID:The prognostic importance of nuclear morphometry and the MIB-1 index in rhabdomyosarcoma [corrected]. 868 24

(PURPOSE). Recently, several reports showed that immunohistochemistry using MIB-1 antibody, which recognizes Ki-67 antigen, is one of the useful methods to determine the proliferative activity in various cancer. To evaluate the prognostic usefulness of the MIB-1, antibody we assessed the cell proliferation immunohistochemically in urothelial cancer. (METHODS). The proliferative activity of thirty cases of renal pelvic and ureteral cancer has been investigated immunohistochemically using MIB-1 antibody, which recognizes Ki-67 antigen, a human nuclear antigen expressed in proliferating cells. (RESULTS). The Ki-67 index correlated with prognostic factors such as pathological stage and histological grade. The patients with early stage or low grade tumors had lower Ki-67 indices. And the Ki-67 index significantly correlated with recurrence and prognosis. The tumors of patients with recurrence or cancer death had higher Ki-67 indices. When the patients were suggrouped according to Ki-67 indices (more than 22%) had significantly worse prognosis even in the same grade. Especially in the grade 2 group, all the four patients in the higher Ki-67 index subgroup had recurred and died of cancer, whereas, in the subgrouped patients with tumors of lower Ki-67 indices, only three patients had bladder cancer recurrence, and no patients had died of cancer, except one case with advanced tumor (T4, N3, M0) resected incompletely. (CONCLUSIONS). These results indicate that the Ki-67 index is a useful prognostic factor and may enhance the prognostic accuracy determined by conventional morphological grading systems.
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PMID:[Evaluation of Ki67 antigen using MIB1 antibody as a prognostic factor in renal pelvic and ureteral cancer]. 869 7

DNA flow cytometry and the monoclonal antibody DO7 were applied in formalin-fixed, paraffin-embedded specimens from 34 primary male breast carcinomas to verify whether DNA ploidy and p53 expression were associated with survival and proliferative activity. They were compared with tumor clinicopathologic features, sex steroid hormone receptors and cell proliferative activity, assessed by the counts of the argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody PC10 against the proliferating cell nuclear antigen and the monoclonal antibody MIB-1. A significant correlation was found between survival and tumor ploidy (median survival, 77 months for diploid but only 38 months for aneuploid cases; P = .03) and p53 expression (median survival, 95 months for cases with p53 scores < or = 14.06% versus 33 for cases with P53 scores > 14.06%; P = .0004; median survival, 99 months for p53 negative vs 39 for positive cases; P = .007). Tumor histological grade (P = .006), AgNOR counts (P = .0001), PC10 scores (P = .002), and MIB-1 scores (P = .001) were also associated with prognosis. In the multivariate analysis, only p53 scores (P = .001) or p53 immunopositivity (P = .003) and AgNOR counts (P = .022) retained an independent prognostic significance. Aneuploid tumors had higher AgNOR counts (P = .002), PC10 (P = .007), MIB-1 (P = .006), and p53 scores (P = .01) than diploid cases. A linear relationship was observed between p53 scores and AgNOR counts (r = .41; P = .014), PC10 (r = .46; P = .005), and MIB-1 scores (r = .44; P = .011). These results indicate that DNA ploidy and p53 expression are associated with survival and cell proliferative activity in male breast carcinoma. Quantitative parameters, such as DNA ploidy, p53 scores, AgNOR counts, PC10, and MIB-1 scores substantially improve the prognostic significance of the traditional parameters in male breast carcinoma.
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PMID:DNA ploidy and p53 expression correlate with survival and cell proliferative activity in male breast carcinoma. 869 11

The postradiosurgical volume changes were compared with preradiosurgical growth fractions defined as the tumor doubling time and/or MIB-1 staining index in 14 patients who underwent gamma knife radiosurgery for treatment of various brain tumors. The mean preradiosurgical observation period using neuroimaging techniques was 750 days (range 80-2967 days), and the mean follow-up period after radiosurgery was 664 days (range 328-1100 days). There were four neurinomas, three meningiomas, two craniopharyngiomas, two gliomas, one hemangioblastoma, one pituitary tumor, and one intracranially infiltrative lacrimal gland tumor. The mean patient age at the time of radiosurgery was 52 years (range 8-81 yrs). There were eight males and six females. Following gamma knife radiosurgery, the mean tumor half time was estimated to be 789 days (range 124-2101 days), and the volume reduction against the preradiosurgical tumor volume ranged from 6.3% to 76.1%. This study demonstrates that gamma knife radiosurgery can control tumor growth despite the lack of a correlation with preradiosurgical tumor growth or staining indices for MIB-1. Analyses of this type are essential to show that an "unchanged tumor volume" as demonstrated by postradiosurgery follow-up neuroimaging can be regarded as showing successful radiosurgery.
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PMID:Gamma knife radiosurgery for brain tumors: postirradiation volume changes compared with preradiosurgical growth fractions. 870 Mar 11

Determination of the cell proliferation activity of neoplasm is useful in making a prognosis. Immunohistochemical detection using MIB-1 monoclonal antibody has recently allowed us to assess tumor cell proliferation easily, because it can be performed on paraffin-embedded specimens and the results have been demonstrated to be positively correlated with the results of PCNA staining. In this study, surgical specimens of 63 pituitary adenomas were examined by immunohistochemical staining with MIB-1 monoclonal antibody. Twenty-nine cases were non-functioning pituitary adenomas, 20 were prolactin (PRL)-producing pituitary adenomas, and 14 were growth hormone (GH)-producing pituitary adenomas. The MIB-1 positive rates of the pituitary adenomas ranged from 0% to 6.46%. In the non-functioning pituitary adenomas, the MIB-1 positive rates ranged from 0% to 4.55% (mean : 0.76%), in the PRL-producing pituitary adenomas the MIB-1 positive rates ranged 0% to 6.46% (mean : 0.91%), and in the GH-producing pituitary adenomas the MIB-1 positive rates ranged 0% to 1.28% (mean: 0.58%). There were no significant differences between these values according to the results of the Wilcoxon signed-rank test. Although the size of the non-functioning pituitary adenomas was not correlated with their MIB-1 positive rate, tumor size was closely correlated with the interval between the onset of the initial symptoms and the date of surgery. In the PRL-producing pituitary adenomas, the MIB-1 positive rate was not correlated with serum PRL levels as an index of secretory activity, but was correlated with the PRL staining positive rate. Preoperative bromocriptine therapy proved effective in reducing tumor size and serum PRL levels, but had no effect on the MIB-1 positive rate. In the GH-producing pituitary adenomas, the MIB-1 positive rate was not correlated with serum GH levels as an index of secretory activity, but was closely correlated with the GH staining positive rate. All three groups included both invasive and noninvasive tumor types, but there were no close statistical correlations between the three tumor types.
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PMID:[The relationship between cell proliferation activity and secretory activity in pituitary adenoma--a review of 63 cases]. 870 57

Based on a computerized microscopy technique, a method has been devised which allows the practising pathologist to easily and rapidly assess quantitatively the relative number of actively proliferating neoplastic parenchymal cells in a tumor nodule. Our method has been tested on a series of 20 conventionally formalin-fixed and paraffin-embedded female mammary adenocarcinomas, using immunoreactivity with the MIB-1 monoclonal antibody against the cell proliferation antigen Ki-67. The values of the proportion of the MIB-1 immunoreactive cell nuclei were compared with those obtained DNA-cytometrically for the fraction of cells in the S-phase; a good correlation was found, although the MIB-1 values were consistently somewhat higher. A prerequisite for a success of the method was, of course, to achieve standardization of the MIB-1 immunostaining technique. By making simple adjustments of it, it could actually be improved to such an extent that almost the same color calibration and thresholding setup could be used. The measuring technique could be either interactive or automatic. The total number of immunoreactive and non-immunoreactive nuclei, as well as the total nuclear area of both cell types were registered in a computerized device. The data were accumulated sequentially for each measure field. To investigate the reproducibility of the immunostaining, two slides of each case were stained on different occasions. Each slide was measured three times; systemically randomly in the x- and y-axis-directions as well as in the subjectively defined histopathologically "most proliferative" area of the tumor. The values obtained were in good agreement with each other and obviously gave some valuable and objective supplementary pieces of information to that of the conventional clinical and histopathologic assessment of the degree of aggressiveness of a malignant neoplasm.
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PMID:A technique for automatic/interactive assessment of the proliferating fraction of neoplastic cells in solid tumors. A methodological study on the Ki-67 immunoreactive cells in human mammary carcinomas, including a comparison with the results of conventional S-phase fraction assessments by means of DNA cytometry. 870 86

Ki-67 nuclear antigen is expressed in upper epithelial levels of intraepithelial neoplasia of the cervix and vulva, variably in condyloma, and in basal and parabasal cells of normal squamous mucosa in histologic preparations. The application of antibodies to Ki-67 as a marker of squamous intraepithelial lesions in cervical smears was explored using either air-dried, acetone-fixed cervical smears obtained from 106 consenting patients or a single slide from archival two-slide cases of squamous intraepithelial lesions MIB-1 monoclonal antibody to Ki-67 was tested using two immunocytochemical techniques. In one set of smears, avidin-biotin peroxidase was used for detection and diaminobenzidine with H2O2 as the chromogen. Some specimens were incubated with 0.3% H2O2 and phosphate buffered saline for blockade of endogenous peroxidase. Alternatively, other air-dried smears were stained using alkaline phosphatase antialkaline phosphatase for detection and new fuchsin as the chromogen. Nuclear staining in squamous intraepithelial lesions was identified in air-dried smears using all of the above methods. Slides stained with avidin-biotin peroxidase and blocked with 0.3% H2O2 and phosphate buffered saline showed less background staining from neutrophils and erythrocytes compared with those without blocking. Slides stained using alkaline phosphatase antialkaline phosphatase showed excessive cytoplasmic staining of endocervical cells, making intraepithelial difficult. No nuclear staining of squamous intraepithelial lesions was observed in destained archival smears. Air-dried smears blocked with 0.3% H2O2 and phosphate buffered saline, incubated with MIB-1, and stained using avidin-biotin peroxidase gave the best results for identification of Ki-67 expression in squamous intraepithelial lesions.
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PMID:Protocol for immunocytochemical detection of SIL in cervical smears using MIB-1 antibody to Ki-67 [corrected]. 872 81

A 54-year-old female presented with a rapidly growing acoustic neurinoma. The tumor doubling time was 216 days or less before surgery and staining indexes for proliferating cell nuclear antigen (PCNA) and MIB-1 were relatively high (4.1% and 2.1%, respectively). The tumor was partially removed, but regrowth was detected with a tumor doubling time of 205 days. She underwent gamma knife radiosurgery for the residual tumor. The periphery of the tumor was irradiated with a dose of 15 Gy. Magnetic resonance imaging 30 months later demonstrated significant tumor shrinkage. The tumor half time following irradiation was determined to be 401 days. Neither surgery nor radiosurgery produced any additional neurological deficit or complications. Gamma knife radiosurgery can control neurinoma growth even when the tumor shows rapid growth and a relatively high growth fraction indicated by high staining indexes for PCNA or MIB-1.
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PMID:Radiosurgery for acoustic neurinoma with rapid growth and relatively high staining indexes for proliferating cell nuclear antigen and MIB-1. 874 Dec 55

Cancer chemoprevention is defined as intervention by chemical agents prior to invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint biomarkers in chemoprevention studies may reduce the size, length and cost of clinical prospective randomized trials in high-risk populations. Intermediate biomarkers are measurable alterations in the tissues at risk and include differentiation, genetic composition, biochemical expression, and proliferation. Assessment is possible because invasive epithelial neoplasms are known to begin as intraepithelial proliferations with a spectrum of cellular abnormalities extending to carcinoma in situ. Genetic heterogeneity begins in the intraepithelial phase; a stochastic accumulation of genetic errors characterizes the progression of clonal evolution within the tumor through the process of invasion and metastasis. Pathologic features associated with this process include tumor classification as well as whether it is intraepithelial or invasive. If the process is intraepithelial, the grade and extent of the intraepithelial lesion are reported. If the neoplasm is invasive, tumor size, extent, degree of differentiation (histologic and nuclear grade), mitotic rate, vascular invasion, and lymph node involvement are evaluated. In assessing biomarkers relevant chemoprevention, and without complete regression of the neoplasm with the chemopreventive agent or agents, measurable parameters along with histopathologic features are applicable. Three methods readily applicable for this purpose that can be applied to paraffin-embedded, formalin-fixed tissue include quantitative pathology, immunohistochemistry, and molecular biologic applications. These methods require some consistency in handling and processing the tissues under study; results may deteriorate due to a number of processing variables, including time to fixation, time in fixative, and fixative type. Quantitative pathology, including static image analysis and flow cytometry, can determine total DNA content. Using static image analysis, very small tumors can be studied. In addition, adjacent intraepithelial and invasive components of a tumor may be studied from a single slide. Steroid receptors, oncogenes, and other proteins detectable through immunohistochemical or molecular biologic methods can be quantitated by this technique as well. Cell cycle synthetic function is assayable by both methods. Flow cytometry can calculate the total percentage of cells in S-phase, or the tumor cell S-phase fraction based on the percentage of cells detected between the G0, G1 peak and the G2 + M peak. A similar approach is generally not applicable with current image analysis equipment; however, cell cycle related proteins such as MIB-1 (Ki-67 associated) can be quantified. Immunohistochemical methods can employ a wide variety of monoclonal antibodies to detect oncogene related proteins, including HER-2/neu (c-erbB-2) and p53. Molecular biologic methods, including in situ hybridization, polymerase chain reaction, and in situ PCR, can have many applications when applied to paraffin-embedded tissues, including detection of viral DNA, identification and measurement of apoptosis, and defining gene deletions.
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PMID:Role of the pathologist in biomarker studies. 874 73


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