Proliferation index and vascular density of giant cell tumors of bone: Are they prognostic markers?

Sulh, Muhammadsamir A.; Greco, M. Alba; Jiang, T; Goswami, Sunanda; Present, David; Steiner, German C.

doi:10.1002/(sici)1097-0142(19960515)77:10<2044::aid-cncr12>3.0.co;2-v

Cited by 27 publications

(11 citation statements)

References 44 publications

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“…Our observation that Ki-67 labeling was confined to the mononuclear cells (Fig 3) is consistent with the literature [18] and confirms that GCTs result in the proliferation of Ki-67 labeling (in brown) is limited to the nuclei of mononuclear cells mononuclear cells as suggested previously [5]. The tumor heterogeneity in Ki-67 labeling that we observed in our study has also been reported in a single GCT [28]. The increase in Ki-67 proliferation index in the recurrent tumor for a given location in the case reported here shows that recurrent tissue may be more aggressive than primary tumors.…”

Section: Discussionmentioning

confidence: 96%

“…However, Ki-67 immunohistochemistry has been studied in single [18] and recurrent GCT [1,28]. Our observation that Ki-67 labeling was confined to the mononuclear cells (Fig 3) is consistent with the literature [18] and confirms that GCTs result in the proliferation of Ki-67 labeling (in brown) is limited to the nuclei of mononuclear cells mononuclear cells as suggested previously [5].…”

Section: Discussionmentioning

confidence: 99%

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Metachronous multicentric giant-cell tumor of the bone in the lower limb. Case report and Ki-67 immunohistochemistry study

et al. 2003

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Multicentric giant-cell tumors of the bone (GCTs) are rare. Little is known about the mechanisms by which these tumors spread and how 1% of GCT turn out to be multicentric. We report the case of a 19-year-old woman with metachronous multiple and recurrent GCTs that were unusual in their pattern of progression along the right lower limb over a 23-year period. Histology showed no evidence of malignant transformation. The treatment was repeated curettage and packing with cement. This did not permit a wide surgical margin, but avoided amputation and preserved full limb function. We tested the proliferation index marker Ki-67 in the tumor specimens. Ki-67 expression was limited to the mononuclear cell component of the tumors. The proliferation index was similar in each new tumor and higher in recurrences for each location. In this case, proliferation was initially low in the new tumor location, despite the time difference and independent from the initial clone evolution. Proliferation index increased in recurrent GCTs after marginal margin resection.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Metachronous multicentric giant-cell tumor of the bone in the lower limb. Case report and Ki-67 immunohistochemistry study

et al. 2003

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“…Giant cell tumor of bone is a locally aggressive tumor whose clinical behavior is difficult to predict based on its microscopic appearance alone (31). Several studies directed toward determining prognostic indicators for these tumors have not identified any.…”

Section: Discussionmentioning

confidence: 99%

Cyclin Alterations in Giant Cell Tumor of Bone

Kauzman

Bradley

et al. 2003

Modern Pathology

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Cyclins play an important role in regulating the passage of dividing cells through critical checkpoints in the cell cycle. Because alterations of several cyclins, especially cyclin D1, have been implicated in the development of many human neoplasms, we examined 32 cases of giant cell tumor of long bones for cyclin D1 gene amplification and protein overexpression using differential polymerase chain reaction and immunohistochemistry, respectively. In addition, the expression of cyclin D3, cyclin B1, and the proliferation-associated antigen Ki-67 (MIB-1) was assessed immunohistochemically. Low-level cyclin D1 gene amplification was detected in 61% of giant cell tumor cases. All tumors showed cyclin D1, cyclin D3, cyclin B1, and Ki-67 (MIB-1) staining; however, the distribution was very characteristic. Cyclin D1 protein expression was seen predominantly in the nuclei of the giant cells, with occasional mononuclear cells staining. There was no correlation between cyclin D1 gene amplification and protein overexpression. Cyclin D3 staining showed a similar distribution, with 88% of cases showing protein overexpression. Cyclin D1 and/or D3 staining in the giant cells was never associated with staining for either cyclin B1 or Ki-67 (MIB-1), as the expression of the latter two proteins was restricted to the mononuclear cells. Cyclin B1 overexpression was seen in 44% of cases. Ki-67 (MIB-1) staining was present in all cases, and between 10 to 50% of the mononuclear cells were positive. These results suggest that alterations in cyclin D1 and/or D3 might play a role in the pathogenesis of giant cell tumor of bone. Alterations of several cell cycle regulatory proteins, especially those involved in the G1-to-S transition, such as D-type cyclins, are detected in many human tumors. Genes encoding D-type cyclins (D1, D2, and D3) are induced by mitogenic stimuli (1) and, together with their catalytic partners CDK4 and CDK6, phosphorylate the retinoblastoma protein (pRb) (2) and allow cells to cross the G1/S restriction point. The cells then become committed to DNA replication and completion of the cell cycle (3). Because D-type cyclins provide the link between mitogenic signals and activation of the cell cycle (1, 4) and because of their regulatory function in the G1-to-S transition (5), constitutive activation of the D-cyclin pathway can reduce or overcome certain mitogen requirements for cell proliferation (6) and thereby contribute to oncogenic transformation (7-9). Although studies suggest that overexpression of cyclin D1 appears to be insufficient on its own to transform primary cells, it may cooperate with other oncogenes to induce transformation (10 -13). Amplification of the cyclin D1 gene and/or overexpression of the protein are observed in a number of human malignancies, such as certain types of epithelial cancers, lymphomas, and some central nervous system tumors (14). Benign and premalignant lesions of the breast (15) and epithelial dysplasias of the oral and laryngeal mucosa (16, 17) also show cyclin D1 alterations, s...

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“…Our case also indicates that almost all giant cells and GCRG of the Temporal Bone some of the mononuclear stromal cells show histiocytic differentiation. There are some reports of the proliferative potential of extracranial GCT 9,23,31,36) and GCRG, 9,29,31) but none about GCT of the skull and only one about GCRG of the skull. 27) In our case, the Ki-67 (MIB-1) index was 7.3%, which is the same as previous cases.…”

Section: Discussionmentioning

confidence: 99%

Giant Cell Reparative Granuloma of the Temporal Bone: Neuroradiological and Immunohistochemical Findings. Case Report.

Yoshimura

Onda

Tanaka

et al. 2002

Neurol. Med. Chir.(Tokyo)

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A 38-year-old man presented with a giant cell reparative granuloma (GCRG) of the left temporal bone. Computed tomography showed a osteolytic middle cranial mass lesion. Magnetic resonance (MR) imaging showed the lesion as low intensity with heterogeneous enhancement by gadolinium on the T 1 -weighted images, and extremely low intensity on the T 2 -weighted images. Angiography showed the lesion as highly vascular and fed by branches of the left external carotid artery. After preoperative embolization, gross total removal of the tumor was performed. The postoperative course was uneventful and no evidence of recurrence has been found for more than 4 years. Histological examination revealed GCRG with multinucleated giant cells in the fibrous background, abundant collagen bundles, hemosiderin deposits, and trabeculae of reactive bone. Some of the mononuclear stromal cells and almost all of the giant cells were positive for CD68, suggesting histiocytic differentiation. These histological features reflect the marked decrease in signal intensity on T 2 -weighted MR images.

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Proliferation index and vascular density of giant cell tumors of bone: Are they prognostic markers?

Abstract: This study presents evidence that the degree of tumor cell proliferation and vascularity are not useful parameters to predict the recurrence of GCT of bone and that there are no significant differences between the PI of mononuclear round-ovoid cells and mononuclear spindle cells.

Cited by 27 publications

References 44 publications

Metachronous multicentric giant-cell tumor of the bone in the lower limb. Case report and Ki-67 immunohistochemistry study

Metachronous multicentric giant-cell tumor of the bone in the lower limb. Case report and Ki-67 immunohistochemistry study

Cyclin Alterations in Giant Cell Tumor of Bone

Giant Cell Reparative Granuloma of the Temporal Bone: Neuroradiological and Immunohistochemical Findings. Case Report.

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