Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Making a histologic distinction between Hurthle cell adenomas and carcinomas sometimes may be difficult. We analyzed a series of Hurthle cell lesions to determine whether specific histologic features and expression of Ki67 and cyclin D1 could be useful in distinguishing Hurthle cell adenomas from carcinomas. Formalin-fixed, paraffin-embedded tissues from 128 Hurthle cell neoplasms, including 59 adenomas; 55 carcinomas; and 14 tumors classified as neoplasms of uncertain malignant behavior (UMB), which had equivocal capsular invasion but no vascular invasion, were analyzed for expression of Ki67 and cyclin D1 by immunostaining. The distribution of immunoreactivity for Ki67 with antibody MIB-1 was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index. None of the patients with adenomas or UMB tumors developed recurrent or metastatic disease after a mean follow-up of 7.8 and 7.9 years, respectively. Of the 55 patients with Hurthle cell carcinoma, 19 were associated with metastatic disease, 13 of whom died with disease. No patient with a Hurthle cell carcinoma without vascular invasion developed metastatic disease. The mean tumor size for Hurthle cell carcinomas (4.8 cm) was significantly larger than that of Hurthle cell adenomas (3.1 cm) or UMB tumors (3.7 cm). No patient with a Hurthle cell tumor smaller than 3.5 cm developed metastatic disease, even when vascular invasion was present. The Ki67 labeling index in Hurthle cell carcinomas (10.0 +/- 1.2) was 3-fold higher than in Hurthle cell adenomas (3.2 +/- 0.3). The Ki67 labeling index in the UMB group was 5.0 +/- 0.7. Cyclin D1 showed diffuse nuclear staining in 1 of the 59 (1.7%) Hurthle cell adenomas, in 10 of the 55 (18%) Hurthle cell carcinomas, and in none of the UMB tumors. In summary, analyses of the cell cycle proteins Ki67 and cyclin D1 in Hurthle cell thyroid neoplasms indicate that these markers may assist in distinguishing some Hurthle cell carcinomas from adenomas. Among the Hurthle cell carcinomas, large tumor size and vascular invasion are associated with clinically aggressive tumors. Our study also suggests that Hurthle cell neoplasms with only equivocal capsular invasion and no vascular invasion should behave in a benign manner.
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PMID:Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid. 1069 77

The purpose of this study was the evaluation of nuclear area, nuclear axis ratio, perimeter and roundness of nuclei of tumor cells with and without Ki-67 antigen expression (demonstrated immunohistochemically using MIB-1 antibody) in primary and metastatic malignant melanoma of the skin. The parameters were further analyzed with respect to their association with the depth of malignant invasion according to Clark [7] and tumor thickness according to Breslow [6]. 142 malignant melanomas (53 primary and 89 metastatic), were assessed employing a computerized image analyzer Quantimet 600S (Leica). The mean nuclear area of MIB-1 positive nuclei was significantly larger than that of the negative ones (p < 0.0001) both in primary and metastatic malignant melanoma. In comparison to the primary melanoma the nuclei of metastatic melanoma cells had a larger area and were more rounded, while the MIB-1 positive nuclei additionally showed a greater degree of polymorphism of their area and shape. With growing invasion thickness according to Breslow and increased Clark's level, the mean nuclear area of tumor cells increased, and their shape became more round. The MIB-1 positive tumor cell nuclei of primary melanomas with metastases were significantly out of round in comparison to primary melanomas without metastases. The results indicate an association between the area and shape of melanoma cell nuclei and the presence of metastases, and between the nuclear area of tumor cells and such factors related to poor prognosis as the depth of invasion and the tumor thickness.
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PMID:Nuclear morphometry of MIB-1 positive and negative tumor cells in primary and metastatic malignant melanoma of the skin. 1072 Dec 63

Malignant uveal melanoma is the commonest primary intraocular tumour in adults. It metastasizes frequently and 50% of patients die within 10 years of diagnosis. The expression of cyclin D1, p53, and MDM2 in uveal melanoma and their relationship to metastasis-free 5-year survival was determined, in order to investigate whether these proteins help to distinguish those patients with a favourable prognosis from those with a poorer one. Ninety-six eyes enucleated for uveal melanomas were immunohistochemically analysed for the protein expression of cyclin D1 and related cell-cycle markers, p53 and MDM2. The evaluation of the specimens was undertaken by two independent pathologists without knowledge of the outcome. Statistical analysis of clinical, morphological, and immunohistological features was performed. A 'favourable outcome' was defined as survival of at least 5 years after diagnosis, without metastases (n=57). An 'unfavourable outcome' was defined as death from metastases within the first 5 years after diagnosis of uveal melanoma (n=39). Cyclin D1 positivity (>15% positive tumour cells) as well as p53 positivity (>15% positive tumour cells) was associated with an unfavourable outcome (for cyclin D1: odds ratio=4. 2, 95% confidence interval 1.5-11.8, p=0.006; for p53: odds ratio=3. 2, 95% confidence interval 1.1-9.3, p=0.03). In addition, cyclin D1 positivity was associated with the presence of extraocular extension of the tumour (p=0.01), with the mixed or epithelioid cell type (p=0. 02), and with the tumour cell MIB-1 positivity (p=0.0001). MDM2 immunoreactivity of the tumour cells showed a potential correlation with clinical outcome (odds ratio=2.1, 95% confidence interval 0.8-5. 8, p=0.13). Multiple logistic regression models showed that cyclin D1 positivity is an independent prognostic factor after control for other prognostic markers. The expression of cyclin D1 in uveal melanoma is associated with a more aggressive course and histologically unfavourable disease. This could serve as a further independent prognostic factor in uveal melanoma.
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PMID:The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma. 1086 67

Evaluation of the malignant potential of phaeochromocytomas in the absence of metastases presents a formidable challenge to both clinicians and pathologists. Until now, no widely accepted clinical, histological, immunohistochemical or molecular method has become available to discriminate malignant from benign phaeochromocytomas. In other endocrine tumours, estimation of proliferative activity by MIB-1 immunostaining has emerged as a promising approach for the determination of metastatic potential. In this study, the utility of MIB-1 immunostaining as a predictive marker for the occurrence of metastases in phaeochromocytomas was evaluated. In addition, the density of S100-positive sustentacular cells was studied, since their depletion has been identified as a negative predictive marker in smaller series. Furthermore, several clinicopathological parameters were evaluated. One hundred and ten patients operated on for a total of 99 benign and 37 malignant phaeochromocytomas were studied. All malignant tumours had documented metastases. The histopathological diagnosis of primary tumours and metastases was reviewed and graded for angioinvasion, capsular extension, and intra-tumoural necrosis. The proliferative index (percentage of MIB-1-positive cells) and the density of S100-positive cells were assessed. In addition, age at resection, associated familial tumour syndromes, tumour size, and tumour location were recorded. Univariate analysis revealed statistically significant correlations between malignancy and proliferative index (p<0.0005) and depletion of S100-positive sustentacular cells (p<0.0005). Fifty per cent of the malignant, but none of the benign phaeochromocytomas had a proliferative index greater than 2.5%. Higher age at resection (p=0. 03), sporadic occurrence (p<0.0005), extra-adrenal location (p<0. 0005), tumour size (p<0.0005), and necrosis (p=0.03) were also significantly associated with malignancy. Logistic regression showed that proliferative index (p=0.0072), size (p=0.0022), and extra-adrenal location (p=0.0012) of the primary tumour were independently predictive for malignancy. In conclusion, this study indicates that assessing the proliferative activity of phaeochromocytomas by MIB-1 immunohistochemistry can predict the occurrence of metastases. The predictive value of S100 immunostaining, tumour size, and extra-adrenal location of the tumour was also confirmed.
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PMID:Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases? 1086 78

The status and role of immunocytes and dendritic cells in regional lymph nodes in patients with gastric cancer are examined in this study. Forty-nine patients with gastric cancer who underwent curative resection were enrolled in the present study. These patients had no lymph node metastases according to a histological examination. The infiltration of natural killer (NK) cells, dendritic cells, and MIB-1-positive immunocytes was investigated. Based on the Japanese Classification of Gastric Carcinoma, regional lymph nodes were divided into three compartments: (a) compartment 1 (lymph node station numbers 1-6); (b) compartment 2 (lymph node station numbers 7-12); and (c) compartment 3 (lymph node station numbers 14 and 16). Dendritic cells and MIB-1-positive immunocytes infiltrated compartment 1 lymph nodes in increased numbers compared with the lymph nodes of compartments 2 or 3 (P < 0.05). Conversely, intranodal NK cell infiltration did not differ significantly among the three compartments. The incidence of intranodal dendritic and MIB-1-positive cell infiltration in patients with submucosal gastric cancer was significantly higher than in patients with tumors that invaded beyond the muscularis propria. The decreased expression of these immunological markers correlated well with recurrent disease, regardless of tumor depth. The immunocyte level is higher in lymph nodes near the primary tumor (compartment 1) than in those that are distant from the tumor (compartments 2 and 3). This pertains to all three markers, i.e., NK, dendritic, and MIB-1-positive cells. Unlike dendritic and MIB-1-positive cells, intratumoral infiltration of NK cells did not correlate well with either lymph node compartment or the depth of tumor invasion. The degree of NK cell infiltration may be directly associated with antitumor effects, especially in compartment 1. A decrease in all three markers is associated with tumor recurrence.
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PMID:Intranodal antitumor immunocyte infiltration in node-negative gastric cancers. 1091 1

We assessed the reliability of prognostic biologic markers by means of immunohistochemistry on cell blocks obtained from diagnostic fine-needle cytopunctures of breast carcinomas and their lymph node metastases. Immunohistochemical studies of MIB-1 (Ki-67), estrogen receptors (ER), progesterone receptors (PR), p53, and c-erb-B-2 were performed in 55 cases of primary breast carcinoma on cell blocks (cytoblock technique) and on their corresponding tissue samples (46 mastectomy specimens and 9 Trucut biopsies) and in 38 cases on cell blocks from fine-needle cytopunctures of both the primary breast tumors and their concurrent lymph node metastases. Interobserver reproducibility ranged from 87 to 100%, depending on the marker. A good correlation was observed between immunostaining assessment on cell blocks and on the corresponding tumor tissues as follows: Ki-67 (85%), ER (96%), PR (82%), p53 (76%), and c-erb-B-2 (84%). An excellent correlation was observed between cell-block results for primary tumors and node metastases; however, a far higher percentage of Ki-67-positive nuclei was observed in the nodes than in the corresponding tumors in seven cases. All nodes corresponding to ER- or PR-negative tumors were also negative, whereas the nodes corresponding to two ER-positive and one PR-positive tumor were negative. Marked discrepancies were also noted with p53 in two cases and with c-erb-B-2 in two cases. Most discrepancies occurred with Trucut biopsies and with breast tumors that contained a large intraductal component. We conclude that cell blocks prepared from fine-needle cytopuncture specimens of breast carcinomas and their node metastases are useful when planning neoadjuvant treatment.
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PMID:Immunohistochemistry on cell blocks from fine-needle cytopunctures of primary breast carcinomas and lymph node metastases. 1095 49

The relationship among histological features, cell kinetics, and clonality has not been studied in adrenal medullary hyperplasias (AMHs) and phaeochromocytomas (PCCs). Thirty-four PCCs (23 sporadic and 11 MEN-2A (multiple endocrine neoplasia type 2A)-related tumours, the latter associated with AMH) from females were included in this study. Representative samples were histologically evaluated and microdissected to extract DNA and evaluate the methylation pattern of the androgen receptor alleles. At least two tissue samples (from the peripheral and internal zones in each tumour) were analysed with appropriate tissue controls run in every case. The same areas were selected for MIB-1 staining and in situ end labelling (ISEL). Malignant PCCs were defined by histologically confirmed distant metastases. All monoclonal AMH nodules from the same patient showed the same X-chromosome inactivated. Six sporadic PCCs revealed liver metastases (malignant PCC) and eight additional sporadic PCCs showed periadrenal infiltration (locally invasive PCC). All informative PCCs were monoclonal, except for five locally invasive PCCs and one benign PCC that revealed polyclonal patterns. Those cases also showed a fibroblastic stromal reaction with prominent blood vessels, focal smooth muscle differentiation, and significantly higher MIB-1 (126.8+/-29.9) and ISEL (50.9+/-12.8) indices. Concordant X-chromosome inactivation in nodules from a given patient suggests that MEN-2A AMH is a multifocal monoclonal condition. A subgroup of PCCs characterized by balanced methylation of androgen receptor alleles, high cellular turnover, and stromal proliferation also shows locally invasive features.
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PMID:Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias: histological and kinetic correlates. 1100 99

BACKGROUND: Assessment of tumor proliferative activity is considered to be the most powerful prognostic factor aside from axillary lymph node status. The purpose of this study is to assess the clinical value of measurement of proliferative activity using the MIB-1 labeling index in patients with breast cancer. METHODS: Surgical specimens from 36 patients with benign breast disorders and146 patients with breast cancer were investigated. The MIB-1 labeling index wasdetermined on the specimens stained by immunohistochemical methods as much as possible. Clinical factors associated with the MIB-1 labeling index were reviewed. RESULTS: The MIB-1 labeling index for non-proliferative disorders, proliferative disorders, and breast cancer was 3.4 +/-1.9%, 8.9 +/-6.2% and 20+/-12%, respectively. The MIB-1 labeling index and tumor size, lymph node metastasis status, and clinical stage according to the TNM classification correlated significantly. Survival rate was inversely correlated with the MIB-1 labeling index. No patientwith an MIB-1 labeling index of less than 10% had lymph node metastases, and all are alive without recurrence. Patients with an MIB-1 labeling index of over 30% had an extremely poor prognosis. CONCLUSION: The MIB-1 labeling index is very useful for predicting both either extremely good or extremely poor prognosis, and axillary lymph node metastasis
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PMID:Prognostic and Therapeutic Implications of the MIB-1 Labeling Index in Breast Cancer. 1109 56

There is preliminary evidence that polymorphism of apolipoprotein E (apoE, protein; APOE, gene), one of the key regulatory proteins in cholesterol metabolism, influences the pathobiology of carcinoma of the colon, prostate and breast and also primary tumours of the brain. This study was designed to determine whether APOE polymorphism is related to variation in the rate of tumour cell proliferation and clinical outcome in carcinoma of the breast. One hundred and eleven infiltrating ductal carcinomas, for which follow up data were available, were included in the study. Estrogen and progesterone receptor status (ER, PR) cell proliferation index (MIB- 1) and APOE genotypes were determined from paraffin-embedded tissue by standard methods. Positive correlations were found between grade and tumour size, grade and presence of metastasis, grade and MIB-1 expression, as well as between ER and PR. Survival correlated inversely with tumour size and the presence of positive lymph nodes. Both steroid receptors correlated inversely with MIB- 1 expression. PR positive status also correlated inversely with high histological grade and presence of lymph node metastases. APOE allele frequencies resembled those of the general population. No significant associations were found between possession of either APOE epsilon2 or epsilon4 alleles and the parameters investigated. Although there is evidence to suggest that APOE epsilon4 may predispose to the development of carcinoma of the breast our data do not support the hypothesis that APOE genotype influences the rate of tumour cell proliferation or the clinical course.
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PMID:Apolipoprotein E polymorphism and breast carcinoma: correlation with cell proliferation indices and clinical outcome. 1111 53

We report the clinical, morphologic, immunophenotypic, and ploidy findings of seven cases of serous borderline tumor of the paratestis. Mean patient age was 56 years (range, 14-77 years), and the clinical presentation was that of a testicular mass. Tumors ranged in size from 1 to 6 cm (mean, 3.5 cm). Six tumors arose from the tunica albuginea, and two of these tumors were intratesticular. One tumor arose from the tunica vaginalis. Serous borderline tumor of the paratestis is histologically identical to its ovarian counterpart. The tumors were cystic with numerous intracystic blunt papillae lined by stratified epithelial cells with minimal to mild cytologic atypia. Psammoma bodies were present in two cases. In all cases, the neoplastic cells stained strongly and diffusely for cytokeratin 7, estrogen receptor, and CD15, and six of seven cases were positive for progesterone receptor and MOC-31. The cells did not stain for cytokeratin 20, carcinoembryonic antigen, calretinin, and HER2/neu. Proliferative activity, as assessed by MIB-1 staining, ranged from 1.3% to 10% (mean, 5.5%). Five of six tumors were diploid, and one was tetraploid. Patients were treated by radical orchiectomy and followed up from 4 months to 18 years (mean, 48 months; median, 8.5 months). No recurrences or metastases occurred. Serous borderline tumor of the paratestis is morphologically and immunophenotypically identical to ovarian serous borderline tumor. To date, no serous borderline tumor of the paratestis reported in the literature or in our series has recurred or metastasized after resection.
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PMID:Serous borderline tumor of the paratestis: a report of seven cases. 1122 8


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