Frequent Upregulation of Cyclin D1 and p16INK4a Expression with Low Ki-67 Scores in Multinucleated Giant Cells

Choi, Jung Woo; Lee, Ju Han; Kim, Young Sik

doi:10.1159/000327359

Cited by 4 publications

(3 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as observed in the present case, it is not present in osteoclasts or OGCs [13,14]. As previously reported OGCs showed expression of protein p16 [15], which was absent in melanoma cells. Ki67 expression was limited to melanoma cells with no positivity in OGCs.…”

Section: Discussionsupporting

confidence: 77%

Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells

Jiménez‐Heffernan

Adrados²,

Muñoz‐Hernández³

et al. 2018

Acta Cytologica

View full text Add to dashboard Cite

Background: Malignant melanoma showing numerous osteoclast-like giant cells (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic literature. The few reported cases seem to have an aggressive clinical behavior. Although most findings support monocyte/macrophage differentiation, the exact nature of OGCs is not clear. Case: A 57-year-old woman presented with an inguinal lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower limb had been excised. Needle aspiration revealed abundant neoplastic single cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells were also present. Nuclei of OGCs were monomorphic with oval morphology and were smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-, Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive behavior with further metastases to the axillary lymph nodes and oral cavity. Conclusion: Numerous OGCs are a rare and relevant finding in malignant melanoma. Their presence should not induce confusion with other tumors rich in osteoclastic cells. Since a relevant number of OGCs in melanoma may mean a more aggressive behavior, and patients may benefit from specific treatments, their presence should be mentioned in the pathologic report.

show abstract

Section: Discussionsupporting

confidence: 77%

Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells

Jiménez‐Heffernan

Adrados²,

Muñoz‐Hernández³

et al. 2018

Acta Cytologica

View full text Add to dashboard Cite

show abstract

“…interleukins 6, 11 and 8, and TNFα; as well as VEGF, placental growth factor (PlGF), hepatocyte growth factor (HGF) and FLt-3 ligand, respectively, some of which can induce proliferation [ 11 , 20 , 21 ]. Earlier studies by others showed the widespread expression of cyclin D1 [ 5 , 6 , 22 – 24 ] cyclin D3 [ 5 ] and p21 WAF1 [ 6 ], less p16 and scarce Ki67 [ 22 ] in GCs. Still, these data were insufficient to declare replication activity in GCs.…”

Section: Discussionmentioning

confidence: 99%

Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?

Maros

Balla

Micsik

et al. 2021

Pathol. Oncol. Res.

View full text Add to dashboard Cite

Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15INK4b, p16INK4a, p27KIP1, p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.

show abstract

“…One such factor, receptor activator of nuclear factor kappa-β ligand (RANKL), has been shown to be highly expressed in another case of uterine sarcoma with osteoclast-like giant cells [6]. Additionally, the expression of cyclin D1 has been shown to be upregulated in osteoclast-like giant cells [14,15]. Cyclin D1 expression has also been shown to be associated the formation of giant cells in some studies, including multinucleation and increased chromosome content [15].…”

Section: Discussionmentioning

confidence: 99%