scholarly journals CCND1 copy number increase and cyclin D1 expression in acral melanoma: a comparative study of fluorescence in situ hybridization and immunohistochemistry in a Chinese cohort

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianying Liu ◽  
Wenjuan Yu ◽  
Fei Gao ◽  
Shuangshuang Qi ◽  
Juan Du ◽  
...  

Abstract Background CCND1 copy number increase is characteristic of acral melanoma and is useful in distinguishing benign and malignant acral melanocytic lesions. Increase of the gene copy number may result in protein overexpression. This raises the possibility that detection of high expression of cyclin D1 by immunohistochemistry (IHC) may be used as a surrogate for direct evaluation of increase in the CCND1 gene copy number. Methods We examined increases in CCND1 copy number with fluorescence in situ hybridization (FISH), and examined cyclin D1 protein expression with IHC in 61 acral melanomas. Results Using FISH, 29 acral melanomas (29/61, 47.5%) showed increase in the CCND1 copy number, including 8 (8/61, 13.1%) which showed low-level increase in the CCND1 copy number and 21 (21/61, 34.4%) with high-level increase in the CCND1 copy number. By analysis of IHC, the median IHC score was 15% (range: 1–80%) in acral melanomas with no CCND1 copy number alteration. In acral melanomas with low-level CCND1 copy number increase, the median IHC score was 25% (range: 3–90%). In acral melanomas with high-level CCND1 copy number increase, the median IHC score was 60% (range: 1–95%). Comparing FISH and IHC, cyclin D1 protein expression level has no corelation with the CCND1 copy number in acral melanomas which have no CCND1 copy number alteration and low-level CCND1 copy number increase (P = 0.108). Cyclin D1 protein expression level correlated positively with CCND1 copy number in acral melanomas with high-level CCND1 copy number increase (P = 0.038). The sensitivity, specificity and positive predictive value of using cyclin D1 IHC to predict CCND1 FISH result was 72.4, 62.5 and 63.6%. Increase in CCND1 copy number was associated with Breslow thickness in invasive acral melanoma. Conclusion High-level increase in the CCND1 copy number can induce high cyclin D1 protein expression in acral melanomas. However low-level increase and normal CCND1 copy number have no obvious correlation with protein expression. Cyclin D1 IHC cannot serve as a surrogate for CCND1 FISH in acral melanomas.

Endocrine ◽  
2005 ◽  
Vol 26 (1) ◽  
pp. 041-044 ◽  
Author(s):  
Gabor Laszlo Kovacs ◽  
Eva Stelkovics ◽  
Laszlo Krenacs ◽  
Gabor Gonda ◽  
Miklos Goth ◽  
...  

2005 ◽  
Vol 289 (6) ◽  
pp. C1457-C1465 ◽  
Author(s):  
Gustavo A. Nader ◽  
Thomas J. McLoughlin ◽  
Karyn A. Esser

The purpose of this study was to identify the potential downstream functions associated with mammalian target of rapamycin (mTOR) signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24, and 48 h. This treatment resulted in significant myotube hypertrophy (protein/DNA) and increased RNA content (RNA/DNA) with no changes in DNA content or indices of cell proliferation. During myotube hypertrophy, the increase in RNA content was accompanied by an increase in tumor suppressor protein retinoblastoma (Rb) phosphorylation and a corresponding increase in the availability of the ribosomal DNA transcription factor upstream binding factor (UBF). Serum stimulation also induced an increase in cyclin D1 protein expression in the differentiated myotubes with a concomitant increase in cyclin D1-dependent cyclin-dependent kinase (CDK)-4 activity toward Rb. The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment, which also prevented the increase in cyclin D1 protein expression, CDK-4 activity, Rb phosphorylation, and the increase in UBF availability. Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D1-dependent CDK-4 activity in the regulation of Rb and ribosomal RNA synthesis. On the basis of these results, we propose that common molecular mechanisms contribute to the regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.


1994 ◽  
Vol 57 (3) ◽  
pp. 353-361 ◽  
Author(s):  
Jirina Bartkova ◽  
Jiri Lukas ◽  
Heiko Müller ◽  
Dorrit Lützhøt ◽  
Michael Strauss ◽  
...  

2000 ◽  
Vol 11 (8) ◽  
pp. 1398-1408
Author(s):  
STEFAN LANG ◽  
ANDREA HARTNER ◽  
R. BERND STERZEL ◽  
HARALD O. SCHÖCKLMANN

Abstract. Hyperplasia of mesangial cells (MC) is a frequent finding in glomerulonephritis. The control and function of cyclin D1, a regulator of cell cycle progression, in MC proliferation in vivo and in vitro were investigated. In a rat model of mesangioproliferative glomerulonephritis, increases in the number of cyclin D1-positive MC nuclei were prominent on day 5 of the disease, preceding the peak of MC hyperplasia. In growth-arrested rat MC in culture, mitogenic stimulation with serum or platelet-derived growth factor (PDGF) led to rapid increases in cyclin D1 protein expression. Transforming growth factor-β1 inhibited PDGF induction of cyclin D1 protein at 12 h. In an examination of the subcellular distribution of cyclin D1, it was observed that stimulation of MC with PDGF for 6 h caused translocation of cyclin D1 from the cytoplasm into the nucleus. Coincubation with PDGF and transforming growth factor-β1 completely inhibited this effect, without altering the cellular cyclin D1 protein abundance at that time point. To test whether reduction of cyclin D1 protein levels was sufficient to inhibit mitogenesis, MC were transfected with antisense oligonucleotides (ODN) complementary to rat cyclin D1 mRNA. Antisense ODN against cyclin D1 reduced the serum- or PDGF-induced protein expression of cyclin D1 to 27 or 10% of control levels, respectively. These inhibitory effects were correlated with diminished cyclin-dependent kinase 4 activity. Antisense ODN against cyclin D1 also decreased the PDGF-induced increase in p21Waf-1 protein levels. The MC proliferation caused by serum or PDGF was markedly inhibited by antisense ODN against cyclin D1, as measured by [3H]thymidine uptake and cell counts. It is concluded that increased cyclin D1 protein expression of MC is required for MC proliferation. Targeting cyclin D1 expression may represent an effective means to inhibit MC proliferation in vitro and in vivo.


1997 ◽  
Vol 111 (7) ◽  
pp. 622-626 ◽  
Author(s):  
Pasquale Capaccio ◽  
Giancarlo Pruneri ◽  
Nadia Carboni ◽  
Angelo Virgilio Pagliari ◽  
Roberto Buffa ◽  
...  

AbstractThe expression of cyclin D1 gene was investigated in 74 laryngeal squamous cell carcinomas (LSCCs) in order to determine its clinical and prognostic value. Overexpression of cyclin Dl was detected immunohistochemically using DCS6 monoclonal antibody on formalin-fixed, paraffin-embedded tissue sections. Cyclin D1 expression was detected in 22 of the 74 cases investigated (30 per cent), thirteen of which presented nodal metastases (59 per cent); of the patients without any detectable cyclin D1 protein expression, six presented nodal metastases (12 per cent). Cyclin D1 protein expression was found in five per cent of the specimens of normal mucosa, eight per cent of thosewith low-grade dysplasia and 20 per cent of those with high-grade dysplasia. A statistically significant association was found between cyclin D1 expression and the supraglottic site (p<0.05), tumour extension (p<0.001), the presence of lymph node metastases (p<0.001), and advanced clinical stage (p<0.001). Cyclin D2 expression analysis is an important tool in the selection of LSCC patients with an aggressive clinical course.


Author(s):  
Judith A. McKay ◽  
Joy J. Douglas ◽  
Val G. Ross ◽  
Stephanie Curran ◽  
Graeme I. Murray ◽  
...  

2007 ◽  
Vol 98 (9) ◽  
pp. 1447-1453 ◽  
Author(s):  
Tomoya Yokota ◽  
Youichirou Matsuzaki ◽  
Makoto Koyama ◽  
Toshiaki Hitomi ◽  
Mayumi Kawanaka ◽  
...  

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