Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features
Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features
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细胞周期调节蛋白（pRb、cyclin D1、p16INK4A 和 cdk4）在人子宫内膜癌中的表达：与临床病理特征的相关性
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发表时间：
2004
影响因子：
2.6
通讯作者：
J. Jakowicki
中科院分区：
文献类型：
--
作者：
A. Semczuk;R. Miturski;D. Skomra;J. Jakowicki
引言.
细胞周期G1/S期控制机制的偏离在癌症的发生和发展中起着重要作用。然而，只有少数报告讨论了恶性子宫内膜肿瘤中同时发生的Rb途径成分异常的问题。方法。
目前，我们评估了48例散发性子宫内膜癌中细胞周期调控蛋白（pRb、cyclin D1、p16 INK 4A和cdk 4）的表达，并研究了这些肿瘤异常蛋白染色与癌症临床病理变量和RB-LOH.Results.
pRb、cyclin D1、p16 INK 4A和cdk 4的阳性率分别为2%、50%、6%和25%。总的来说，48例子宫内膜恶性肿瘤中有33例（69%）在免疫组化上显示至少一种Rb通路蛋白的异常表达。细胞周期调控因子、pRb、p16 INK 4A和cyclin D1异常的频率与肿瘤的临床病理变量之间均无显著相关性，但cdk 4染色与肿瘤的临床分期之间存在显著相关性（P<0.05，Fisher精确检验）。CDK 4表达与患者年龄呈负相关（r=-0.367; P=0.01）。除pRb外，其他细胞周期调控蛋白均与13 q14位点的杂合性丢失无关。
因此，Rb-通路组分，特别是细胞周期蛋白D1和cdk 4的脱轨似乎参与了人类子宫内膜癌的发展。cdk 4的过度表达与肿瘤性疾病的进展有关，并与发病年龄相对应，这表明cdk 4免疫反应性的改变在子宫内膜癌的进展中起着重要作用。
AbstractIntroduction.
Derailments of the control mechanisms in the G1/S phase of the cell cycle play a fundamental role in the initiation and progression of cancer. However, only a few reports have addressed the issue of simultaneously occurring abnormalities of Rb-pathway components in malignant endometrial tumors.Methods.
Currently, we assessed the expression of cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in 48 sporadic endometrial cancers, and investigated these tumors for a possible relationship between aberrant protein staining and clinicopathological variables of cancer and RB-LOH.Results.
There was abnormal pRb, cyclin D1, p16INK4A and cdk4 immunoreactivity in 2%, 50%, 6% and 25% of cases, respectively. Altogether, 33 of 48 (69%) endometrial malignant tumors showed abnormal expression of at least one Rb-pathway protein immunohistochemically. However, there was significant correlation neither between the cell-cycle regulators nor between the frequency of pRb, p16INK4A and cyclin D1 abnormalities and clinicopathological variables of cancer, but a significant correlation did exist between cdk4 staining and the clinical stage of disease (P<0.05, Fisher's exact test). Moreover, an inverse relationship was also demonstrated between cdk4 expression and patient age (r=-0.367; P=0.01). However, none of the cell-cycle regulatory proteins, except for pRb, was related to loss of heterozygosity at locus 13q14.Conclusion.
As a conclusion, derailments of the Rb-pathway components, cyclin D1 and cdk4 in particular, seems to participate in the endometrial cancer development in humans. Overexpression of cdk4 was related to the progression of neoplastic disease and corresponds with age of onset, suggesting a major role of altered cdk4 immunoreactivity in the progression of endometrial cancer.
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影响因子：
11.2
作者：
M. Schutte;R. Hruban;J. Geradts;R. Maynard;W. Hilgers;S. Rabindran;C. Moskaluk;S. Hahn;Irmgard Schwa
通讯作者：
M. Schutte;R. Hruban;J. Geradts;R. Maynard;W. Hilgers;S. Rabindran;C. Moskaluk;S. Hahn;Irmgard Schwa
影响因子：
11.2
作者：
John Easton;T. Wei;J. Lahti;Vincent J. Kidd
通讯作者：
John Easton;T. Wei;J. Lahti;Vincent J. Kidd
影响因子：
56.9
作者：
KAMB, A;GRUIS, NA;SKOLNICK, MH
通讯作者：
SKOLNICK, MH
影响因子：
4.5
作者：
Abid-Essefi, S;Baudrimont, I;Bacha, H
通讯作者：
Bacha, H