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Query: UMLS:C0027651 (tumor)
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Considerable clinical and radiologic similarity exists among FB, ABP, MIB, ABPA, and, to a lesser extent, BCG. In the absence of focal obstructive lesions such as tuberculosis or neoplasm, one of the diffuse bronchial hypersecretory diseases, that is, bronchial asthma, acute or chronic bronchitis, asthmatic bronchitis, or cystic fibrosis, is prerequisite to the development of a clinical and radiologic syndrome, resulting from bronchial mucus retention. This hypersecretory bronchial obstruction syndrome characterizes each of the disorders discussed. Thus, the differences existing among these disorders are merely those of size and location of mucus plugs or casts, and there is substantial variation within each individual entity concerning even this aspect. Unfortunately, extensive efforts to elucidate immunopathogenesis exist only for ABPA. Although evidence for the immunologic and morphologic presence of fungi, particularly AF, in ABPA is quite compelling, it is not necessarily conclusive evidence for an etiologic role of AF in the immunopathogenesis of this disorder. In this regard, it is reasonable to speculate that, perhaps, similar immunologic and morphologic information exists for FB, ABP, MIB, and, in some cases, BCG. BCG, because of its unique intrinsic bronchial obstructive and destructive histopathology, is a disorder distinct from the others, though sharing common clinical and radiologic features in some instances. If Aspergillus is involved in the immunopathogenesis of this disease, it cannot be the only etiologic factor, since in many instances no evidence of its presence is found.
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PMID:Bronchocentric granulomatosis and allergic bronchopulmonary aspergillosis. 306 92

The bcl-2 protooncogene encodes a 26-kD protein that extends cell survival by blocking apoptosis. This protein has been found to be overexpressed in neoplastic neural cell lines, although its expression in reactive and neoplastic astrocytes in vivo has not been well characterized. The authors hypothesized that bcl-2 oncoprotein expression in gliomas might be positively correlated with the tumor's degree of malignancy. Sixty-three gliomas of various subtypes and histological grades were immunostained by bcl-2 protein and the percentage of positive cells was quantitatively assessed. All tumors contained neoplastic cells that were immunoreactive for the bcl-2 protein (range of cell positivity 1%-53%). It was found that bcl-2 expression did not vary significantly as a function of tumor subtype or grade (p < 0.1, one-way analysis of variance (ANOVA) on ranks) as compared to the cell proliferation marker Ki-67 (MIB-1) in which a very significant correlation with tumor grade was noted (p < 0.0000001, one-way ANOVA on ranks). In fact, the highest percentage of bcl-2 immunoreactive cells was noted in low-grade gliomas, that is, in juvenile pilocytic astrocytomas and oligoastrocytomas. The specificity of bcl-2 overexpression was also assessed in 10 nonneoplastic lesions associated with prominent reactive astrocytosis. In nine of these cases (90%), bcl-2-positive reactive astrocytes were observed, often in large numbers, whereas relatively few Ki-67 immunoreactive cells were noted. The authors conclude that bcl-2 oncoprotein expression as assessed immunohistochemically does not correlate with glial tumor type or grade and its overexpression is not confined only to neoplastic conditions. Instead, the finding of robust bcl-2 expression in low-grade glial tumors and in reactive astrocytes warrants the inference that resistance to apoptosis is a nonspecific finding in astrocytes associated with both reactive and neoplastic conditions.
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PMID:Expression of bcl-2 in reactive and neoplastic astrocytes: lack of correlation with presence or degree of malignancy. 749 Jun 15

Although many histologic criteria have been utilized to help distinguish benign from malignant adrenocortical tumors, it still may be difficult to assess the biologic potential of a given tumor. We evaluated 19 adenomas and 15 primary carcinomas with the avidin-biotin complex peroxidase method utilizing formalin-fixed, paraffin-embedded tissues with monoclonal antibodies for proliferating cell nuclear antigen (PC10) and Ki-67 (MIB 1) to determine if staining for these antigens could be used to help differentiate benign from malignant adrenocortical neoplasms. We also evaluated whether these markers could be used as prognostic indicators. Labeling indices for both PCNA and Ki-67 were determined by enumerating 1000 tumor cells, and expressed as a percentage of cells with nuclear staining. A PCNA and a Ki-67 score was obtained by the product of the staining intensity (0-3+) and the extent of nuclear staining, expressed as an estimate of the percentage of cells staining. Both PCNA and Ki-67 score and labeling index were correlated with mitotic counts, histologic diagnosis, and clinical outcome. Follow-up period for patients ranged from 4 months to 12 years with a mean of 25 months. Mitotic counts correlated with histologic diagnosis and clinical outcome. Both Ki-67 score and labeling index were significantly higher in malignant than in benign tumors, and correlated with mitotic counts and clinical outcome. There was a strong correlation between Ki-67 score and labeling index, indicating that Ki-67 score may be a more rapid and equally accurate method of estimating proliferative index of a tumor. PCNA score and labeling index did not correlate with histologic diagnosis or clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical assessment of proliferative activity in adrenocortical neoplasms. 750 13

The proliferative activity of male breast carcinoma has been investigated using the staining of the argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody against the proliferating cell nuclear antigen (PC10) and the monoclonal antibody MIB-1 in formalin-fixed, paraffin-embedded specimens from 27 primary male breast carcinomas at diagnosis. A significant correlation was found between survival and AgNOR counts (median of survival 77 months for cases with AgNOR/cell < or = 7.27 but 37 months only for cases with > 7.27 AgNOR/cell; P = 0.001), proliferating cell nuclear antigen scores (median of survival 73 months for cases with proliferating cell nuclear antigen < or = 18.25% versus 41 for cases with proliferating cell nuclear antigen > 18.25%; P = 0.013) and MIB-1 scores (median of survival 73 months for cases with MIB-1 scores < or = 23.5% versus 37 months for cases with MIB-1 scores > 23.5%; P = 0.01). Tumor histological grade was also correlated with prognosis (median of survival 72 months for grade 2 versus 33 months for grade 3 tumors; P = 0.01). Estrogen and progesterone receptors, immunohistochemically detected on paraffin-embedded sections, had no prognostic value. In the multivariate survival analysis, only AgNOR counts (P = 0.007) and tumor size (P = 0.003) had an independent prognostic significance. Our results indicate that methods for assessing the cell proliferation in routinely processed specimens offer significant prognostic information in male breast carcinoma. The finding, together with the lack of prognostic significance for estrogen receptors and progesterone receptors, suggests that male breast carcinoma is biologically different from female breast cancer.
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PMID:Proliferative activity is a significant prognostic factor in male breast carcinoma. 751 30

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.
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PMID:The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials. 752 57

We investigated the expression and distribution of the extracellular matrix protein tenascin (TN) in 59 astrocytomas and 11 samples of normal brain by Western blot analysis and immunohistochemistry using antibodies against human TN. The tumors included 14 juvenile pilocytic astrocytomas (grade 1), 13 low grade fibrillary astrocytomas (grade II), 8 anaplastic astrocytomas (grade III), and 24 glioblastomas multiforme (grade IV). Proliferation indices were calculated by computer-based image analysis after immunostaining with the MIB-1 antibody against the Ki-67 proliferation-associated antigen. Western blot analysis for TN on fresh frozen tumor tissue from 23 of the 59 astrocytomas indicated up to 4-fold higher TN expression in glioblastomas multiforme than in nontumorous control tissues. Enhanced intercellular expression of TN was observed by immunohistochemistry in glioblastomas multiforme. More-over, TN immunostaining was consistently greater within and around the walls of hyperplastic blood vessels than nonhyperplastic vessels of both high grade tumors and juvenile pilocytic astrocytomas. Juvenile pilocytic astrocytomas with increased TN expression by Western blot analysis had vascular hyperplasia by light microscopy. Proliferation indices moderately correlated with tumor grade. Enhanced immunohistochemical expression of TN was associated with higher tumor grade with higher proliferation indices. The strong association of TN and vascular hyperplasia, regardless of tumor grade, suggests that TN may play a crucial role in angiogenesis.
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PMID:Tenascin expression in astrocytomas correlates with angiogenesis. 753 17

Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous flow cytometric studies at Indiana University demonstrated a significant correlation between high proliferative activity and metastatic disease. The current study evaluated the prognostic significance of immunohistochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 pathologic Stage A, 17 with metastatic disease) was reviewed and immunohistochemically stained for Ki-67 antigen (MIB-1), proliferation-associated nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-related antigen (neovascularization). Staining with MIB-1 was significantly higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) and was predictive of metastatic status with a sensitivity of 82% and specificity of 69%. In this study, no patient with a MIB-1 value less than 52% had metastases. Proliferation-associated nuclear antigen and p53 staining correlated with MIB-1 values (R = 0.63 and 0.55, respectively) but did not correlate with metastatic status. Tumor angiogenesis was also not predictive of metastatic status. Assessment of proliferation rates using MIB-1 antibody in clinical Stage A nonseminomatous germ-cell-tumor patients may prove helpful in predicting metastatic status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors. 754 14

In an effort to optimize immunocytochemical methods to evaluate cell kinetics in brain tumors, we studied two newly-developed antibodies which react with formalin resistant epitopes of Proliferating Cellular Nuclear Antigen (PCNA) and Ki-67. These results were compared with standard flow cytometric cell cycle data from the same tumor specimens to determine if these methods correlate with each other, and whether retrospective analysis using these antibodies is feasible for cell kinetic analysis of brain tumors. Thirty-one specimens of glial tumors submitted for flow cytometry during 1992 were also reacted with antibodies to PCNA (PC-10) and Ki-67 (MIB-1). Flow cytometry scores for S-phase Fraction were compared with immunocytochemical scores for both antibodies, using an arbitrary rating of 1 (low, < 4%), 2 (intermediate, 4-6%), 3 (high, > 6%), and 1 (< 25% positive), 2 (26-75% positive), 3 (> 75% positive), respectively. MIB-1 results were found to correlate significantly with the S-phase fraction as determined by flow cytometry. The MIB-1 data showed a trend toward underestimating, i.e., lower scores, the proliferative index compared with flow cytometry. There was less of a correlation between PC-10 antibody scores and flow cytometry S-phase fraction, as PC-10 immunostaining typically overestimated the proliferative rate of brain tumors when compared with flow cytometry. There was an exact correlation between PC-10 and MIB-1 in only 4 cases, whereas in the remaining specimens, PC-10 results were always higher than MIB-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of proliferative grade in glial neoplasms using antibodies to the Ki-67 defined antigen and PCNA in formalin fixed, deparaffinized tissues. 756 3

Inflammatory pseudotumor (IPT) truly represents an enigmatic entity. A tumor-like lesion known with many synonyms according to the various patronymic authors who named it on the basis of the different observed morphological appearances. Among these names plasma cell granuloma, plasma cell/histiocytoma complex, xanthomatous pseudotumor, xanthoma, fibrous xanthoma, histiocytoma, xanthogranuloma, inflammatory myofibroblastic tumor, inflammatory myofibrohistiocytic proliferation are just the most renown. The enigma consists in the fact that it can easily be misunderstood as a sarcoma with a marked inflammatory component just as reciprocally an inflammatory sarcoma can be misinterpreted as an IPT. As it was not enough some authors believe that some so-called IPT actually represent or may evolve into a true neoplastic process. For this reason a big debate has been raised concerning the biologic behaviour of this entity and a sense of scepticism often surrounds pathological diagnoses termed under this rubric. The predominant pattern is that of a plasma cell infiltration with a definitely histiocytic component and mostly bland spindle shaped cells which occasionally can look somewhat atypical, and can form fascicles in some areas. Anyway putting apart diagnostic misinterpretations, IPT pathogenetically is intended as the result of an inflammatory process mediated locally by an inappropriate production of monokines. It has been described in many different anatomic visceral and somatic sites, from the classical ones such as soft tissues and retroperitoneum to the most unusual such as nervous system and its covering to the most recently observed such as skin or lymph nodes or salivary glands. Breast is definitely an exoteric site of location of such kind of lesion. Only one case has previously been described. This case regards a lady aged 38 years which was locally treated by surgical excision: this case aside the standard microscopic examination was also studied immunohistochemically including proliferation markers (Ki-67/MIB-1) and on flow cytometry which are helpful means to confidently diagnose such entity. The differential diagnoses and diagnostic difficulties concerning the correct interpretation of this lesion are dealt with.
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PMID:[Inflammatory pseudotumor of the breast. Report of a case and review of the literature]. 756 68

The applicability of MIB-1, a monoclonal antibody directed against the Ki-67 antigen, was studied in the PC-82 and LNCaP prostatic tumor models at various levels of proliferative activity. Statistically significant correlations were found in LNCaP cultures between Ki-67 and MIB-1 scores (r = 0.84, P < 0.001), and in PC-82 tumors between MIB-1 scores and paraffin tissue Ki-67 (pKi-67) (r = 0.90, P < 0.001), frozen tissue (fKi-67) (r = 0.86, P < 0.001), and BrdU uptake (r = 0.70, P < 0.001), respectively. pKi-67 scores were double the fKi-67 scores, which may be due to methodological differences. MIB-1 scores exceeded both the fKi-67 and pKi-67 scores. The affinity of MIB-1 for the antigen is much higher than the affinity of Ki-67, which may explain the differences. MIB-1 is a promising means of evaluating the presence of only minute amounts of the Ki-67 antigen in paraffin-embedded human tumor material, especially in relatively slowly growing tumors.
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PMID:Determination of Ki-67 defined growth fraction by monoclonal antibody MIB-1 in formalin-fixed, paraffin-embedded prostatic cancer tissues. 756 94


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