p16、Rb和cyclin D1蛋白在横纹肌肉瘤中的表达及其意义

目的：探讨细胞周期相关蛋白表达异常与横纹肌肉瘤（RMS）的关系。方法：应用S－P免疫组化方法观察p16,Rb和cyclinD1蛋白在RMS中的表达状态。结果：p16,Rb和cyclinD1蛋白表达阳性率分别为55．3％,61．7％和51．1％,在胚胎性横纹肌肉瘤（ERMS）,p16和Rb蛋白表达阳性率为75．0％（21／28）和67．9％（19／28）,明显高于在腺泡状横纹肌肉瘤（ARMS）中的表达（P＜0．05）,p16蛋白阳性率在I,Ⅱ级横纹肌肉瘤分别为75．0％和73．3％,高于Ⅲ级横纹肌肉瘤（45．0％）;p16蛋白阴性及cyclinD1蛋白过表达组,局部浸润,复发或转移发生率高于p16蛋白阳性及cyclinD1蛋白阴性组;11／47例（23．4％）出现两种以上蛋白表达异常。结论：P16,Rb和cyclinD1蛋白异常可能与部分横纹肌肉瘤发生发展有关,且横纹肌肉瘤的发生可能涉及两种以上基因异常。     

Alterations of expression of Rb,p16INK4A and cyclin D1 in non-small cell lung carcinoma and their clinical significance

Inactivation of the Rb pathway in non-small cell lung carcinoma (NSCLC) occurs mostly through inactivation of the cyclin-dependent kinase inhibitor p16^INK4A and/or up-regulation of cyclin D1. In order to assess the frequency and the prognostic value of these abnormalities in NSCLC, immunohistochemical analysis of Rb, p16^INK4, and cyclin D1 has been performed on 168 cases of NSCLC including 77 squamous cell carcinomas, 43 adenocarcinomas, and 48 basaloid carcinomas. The reduced survival rate of basaloid carcinoma (stage I–II) compared with other histological types of NSCLC was confirmed (p = 0·008). Loss of protein expression of Rb and p16^INK4A was observed in 12 per cent and 58 per cent of NSCLC cases respectively and cyclin D1 overexpression in 43 per cent. There was an inverse correlation between Rb and p16 expression ( p < 0·0001) and a direct correlation between Rb and cyclin D1 expression ( p = 0·0007). In univariate analysis, Rb-negative adenocarcinomas at stages I–II had a significantly shorter survival than Rb-positive cases ( p = 0·04) and stages I–II p16-positive cases had a shorter survival than p16-negative cases ( p = 0·02), which was more significant in basaloid carcinoma ( p = 0·003). p16 status retained its influence on survival in multivariate analysis at stage I–II for all cases ( p = 0·01) and for basaloid carcinoma ( p = 0·005). Cyclin D1 overexpression did not influence survival. Combined Rb/p16/cyclin D1 phenotypes in univariate analysis showed a shorter survival for Rb-negative/p16-positive/cyclin D1-negative tumours ( p = 0·002). These results, linked to previous data, indicate that the Rb pathway of G1 arrest is initially disrupted in the vast majority of NSCLCs (83 per cent), but could not confirm an unfavourable role for each individual event (p16^INK4A loss or cyclin D1 up-regulation) in prognosis. Copyright © 1999 John Wiley & Sons, Ltd.     

Expression of pRb, p53, p16 and cyclin D1 and their clinical implications in urothelial carcinoma

The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.     

High-level cytoplasmic cyclin D1 expression in lymph node metastases from prostate cancer independently predicts early biochemical failure and death in surgically treated patients

Fleischmann A, Rocha C, Saxer‐Sekulic N, Zlobec I, Sauter G & Thalmann G N
(2011) Histopathology 58 , 781–789
High‐level cytoplasmic cyclin D1 expression in lymph node metastases from prostate cancer independently predicts early biochemical failure and death in surgically treated patients Aims: To test the prognostic significance of cyclin D1 in nodal‐positive prostate cancer. Methods and results: Nuclear and cytoplasmic cyclin D1 expression was evaluated in 119 nodal‐positive prostate cancer patients undergoing radical prostatectomy and extended lymphadenectomy. Cyclin D1 was correlated with various tumour features and biochemical recurrence‐free survival (bRFS), disease‐specific survival (DSS) and overall survival (OS). In the metastases, high‐level cytoplasmic cyclin D1 expression independently predicted poor outcome (5‐year bRFS, 12.5% versus 26.4%, P = 0.006; 5‐year DSS, 56.3% versus 80.7%, P = 0.007; 5‐year OS, 56.3% versus 78.7%, P = 0.011). These patients had a 2.62‐fold elevated risk of dying from prostate cancer as compared with patients with low‐level cytoplasmic cyclin D1 expression (P = 0.024). All other subcellular compartments of cyclin D1 expression in primary tumours and metastases were prognostically non‐significant. Conclusions: The subcellular location of cyclin D1 expression in prostate cancer is linked to specific clinical courses. Survival stratification according to biomarker expression in metastases indicates an important role for tumour sampling from these tissues.     

Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationships to cell proliferation, apoptosis, and tumour progression in invasive ductal carcinoma of the breast

In order to understand the intricate relationship of cell proliferation and apoptosis in tumour development, proliferation markers (Ki-67 and c-myc), apoptosis, cell-cycle inducers cyclin D1 and D3, and cell-cycle inhibitors p16(INK4), p21(CIP1), and p27(KIP1) were evaluated in ductal breast carcinoma. The heterogeneous nature of breast tumours provides a system by which the changes in cell-cycle genes can be explored under a wide range of proliferation and apoptotic indices. To address the above issues, immunohistochemical studies were conducted in 40 pairs of tumours and adjacent normal ductal tissues. The TUNEL method was used to identify apoptotic cells. Except for p27/KIP1, the proliferation (Ki-67, c-myc) and the apoptotic indexes together with levels of p16/INK4a, p21/CIP1, cyclin D1, and cyclin D3, were clearly elevated among tumour tissues, while absent in the adjacent normal tissues. Spearman correlation analysis indicated strong associations among apoptotic index, Ki-67, c-myc, and tumour grade. In addition, p21/CIP1 and cyclin D3 were positively correlated, while p16/INK4a, p27/KIP1, and cyclin D1 were negatively correlated with tumour grade. There was clear decoupling between p21 and p27, as well as decoupling between cyclin D1 and cyclin D3, in terms of their relationship to cell proliferation and apoptosis, indicating differential roles in tumour progression.     

Analysis of the Cycilin D1/p16/pRb Pathway in Parathyroid Adenomas

Cyclin D1/p16/pRb pathway controlling G1→S cell cycle checkpoint is frequently altered in human tumors. Currently, scarce data are available for parathyroid tumors. We have studied 46 parathyroid adenomas (PTAs) and 12 normal parathyroid glands (PTGs) by immunohistochemistry with cyclin D1 (CD1), p16, pRb, and Ki-67 antibodies. We observed CD1 expression in 89%, p16 in 70%, and pRb in 100% of PTAs. Statistically significant differences with normal PTGs were found only concerning p16 expression (p<0.05). Proliferating rate (Ki-67) was always low, although significantly higher than in normal PTGs. Our findings demonstrate the presence of alterations in the CD1/p16/pRb pathway in PTAs, consisting in p16 overexpression apparently unrelated to pRb downregulation. On the other hand, we did not find significant differences in CD1 expression between PTAs and normal PTGs, suggesting CD1 overexpression could be a physiological event in parathyroid tissue.     

Cyclin-dependent kinase inhibitor p27Kipl expression and interaction with other cell cycle-associated proteins in mammary carcinoma

p27, cyclin D1, and retinoblastoma (Rb) protein have been demonstrated using immunohistochemistry in 189 cases of primary breast carcinoma with long-term follow-up. There was a statistically significant association between the expression of p27 and both cyclin D1 and the retinoblastoma gene product (pRb), corresponding to their close interactions in regulating the G₁/S transition in the cell cycle. Low levels of p27 were seen in high-grade, rapidly proliferating, oestrogen receptor-negative tumours. In univariate analysis, low p27 expression was associated with a reduced relapse-free and overall survival. In multivariate analysis, p27 was not an independent predictor of survival when either histological grade or proliferative activity (S-phase fraction) was included in the model. When the combined expression of p27 and cyclin D1 was related to survival, patients with high levels of p27, regardless of their cyclin D1 status, did well, whilst those with low p27 had a poor outcome. The only exception, in the latter group, was patients with tumours expressing high levels of cyclin D1, who did as well as the high p27 group. We have shown that in clinical material p27 expression is associated with proliferative activity and while univariate analysis shows it to be a significant indicator of prognosis, this significance is lost in multivariate analysis when traditional prognostic factors are included in the model. The interest in p27 expression in mammary carcinoma lies in its behaviour when examined in combination with other G₁ cell cycle regulators. Copyright © 1999 John Wiley & Sons, Ltd.     

Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status

p21Waf1 (p21), p27Kip1 (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, studies on these cell cycle regulators in ductal carcinoma in situ (DCIS) have been extremely limited. Therefore, we studied the immunohistochemical expression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared the findings with the clinicopathologic parameters (age, tumor size, gross type, histologic type, histologic grade, necrosis and mitotic index), p53 and estrogen receptor (ER) status. A significant correlation was found between positive p21 immunoreactivity (67.3% of the cases) and well-differentiated histologic grade, non-comedo type, ER-positive and p53-negative (p53-) status. DCIS with p21+/p53- is likely to be the non-comedo type. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) correlated with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cyclin D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.     

cyclinD1、p16、Rb在胸腺瘤中表达及预后意义

目的：探讨ｃｙｃｌｉｎ Ｄ１、ｐ１６、Ｒｂ蛋白在胸腺瘤中表达及预后意义。方法；应用免疫组化Ｓ－Ｐ法，对５４例胸腺瘤标本进行检测。结果：ｃｙｃｌｉｎＤ１、ｐ１６，Ｒｂ蛋白在髓质型，混合型胸腺瘤中阳性表达率分别为２３．１％（３／１３）、６９．２％（９／１３），５３．９％（７／１３），器官样，普通皮质型胸腺瘤中阳性表达率分别为５０．０％（８／１６）、７５．０％（１２／１６）、７５．０％（１２／１６），高     

结直肠癌中cyclin D1和p27蛋白的表达及其意义

目的　研究cyclinD1和p2 7蛋白在结直肠癌发生、发展中的作用及其与结直肠癌临床病理特征关系。 方法　收集5 8例手术切除的结直肠癌标本 ,同时取距癌灶 >5cm的正常组织 ,应用免疫组化S P法检测癌组织及正常组织中cyclinD1和p2 7蛋白的表达。结果　cyclinD1蛋白在结直肠癌的表达阳性率为 5 5 17%,正常组织无表达 (P <0 0 1) ;cyclinD1蛋白的表达阳性率在 6 0岁以上年龄组高于 6 0岁以下年龄组 (P <0 0 5 ) ;cyclinD1蛋白的表达与肿瘤组织分化程度负相关 (P <0 0 1)。p2 7蛋白在结直肠癌的表达阳性率为 5 5 17%,在结直肠正常组织的表达阳性率为 96 5 5 %(P <0 0 1) ;p2 7蛋白的表达与肿瘤组织分化程度负相关 (P <0 0 1)。cyclinD1和p2 7蛋白在结直肠癌的表达呈正相关 (r =0 5 82P <0 0 1)。 结论　cyclinD1蛋白过表达与 p2 7蛋白失活可加速细胞周期转化 ,促进结直肠癌的发生 ,cyclinD1和 p2 7蛋白的检测可作为评价结直肠癌恶性程度和判断预后的重要指标。     

Cyclin D1 and p16 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid gland

AIMS: To compare cyclin D1 and p16(ink4) (p16) expression in normal tissue, pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland. METHODS AND RESULTS: Immunohistochemistry was used to examine cyclin D1 and p16 expression in 43 parotid tumours (29 PAs and 14 CXPAs). Cyclin D1 and p16 were both significantly more likely to be expressed in the neoplastic than in the normal epithelial and stromal components of PA and CXPA (P < 0.001 and P < 0.005, respectively). Cyclin D1 was more likely to be expressed in the malignant components of CXPA than in the benign components of PA (50% versus 31% and 31%, respectively), but the trend was not statistically significant. There was no evidence of this association for p16 (corresponding positivity rates 69% versus 81% and 52%). CONCLUSIONS: Our findings provide preliminary evidence of roles for cyclin D1 and p16 in the development of PA and for cyclin D1 in the progression of PA to CXPA.     

Differential expression of cdk inhibitors p16, p21cip1, p27kip1, and cyclin E in cervical cytological smears prepared by the ThinPrep method

Our objective was to correlate p16, p21cip1, p27kip1, and cyclin E protein expression with the degree of dysplasia on ThinPrep Papanicolaou (Pap) smears using a modified immunoperoxidase staining. Smears read as normal, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or high-grade SIL (HSIL) were identified and tested for high-risk human papillomavirus (HR-HPV). Additional smears were processed for immunoperoxidase for p16, p21cip1, p27kip1, and cyclin E. Thirty-four smears were satisfactory for study. The p16 was positive in all nine HSIL, in four of nine LSIL, and in one of seven ASC-US. The p27kip1 was positive in all nine HSIL, in eight of nine LSIL, and in one of seven ASC-US. The p21cip1 was positive in all nine HSIL, in one of nine LSIL, and in one of seven ASC-US. Cyclin E was positive in seven of nine HSIL and in one of nine LSIL and in none of the ASC-US smears. Normal smears were negative for all the antigens. There was poor correlation of protein expression and HR-HPV infection. We concluded that p16, p21cip1, p27kip1, and cyclin E can be demonstrated on Pap smears and they are expressed differentially in dysplastic cells, with highest expression in HSIL. The p21cip1 and cyclin E showed the greatest correlation with HSIL.     

Overexpressions of Cyclin B1, cdc2, p16 and p53 in human breast cancer: the clinicopathologic correlations and prognostic implications

Purpose

The molecular mechanisms that are responsible for the initiation and progression of breast cancers are largely unknown. This study was to analyze the cyclin B1, cdc2, p53 and p16 tumor suppressor genes in human breast cancer.

Materials and Methods

To investigate the role of cyclin B1, cdc2, p53 and p16 in the pathogenesis and progression of breast carcinomas, 98 cases of breast cancers were examined by immunohistochemical method. The correlations of cyclin B1, cdc2, p53 and p16 expression with various clinico-pathologic findings were analysed.

Results

In the normal breast tissues, cyclin B1, cdc2 and p16 were weakly expressed, while p53 was not expressed. On the other hand, cyclin B1, cdc2, p53 and p16 were overexpressed in breast cancer, showing correlation between the expression of cyclin B1 and cdc2 and breast cancers (p=0.00). The overexpressions of cdc2 and p16 were correlated with an infiltrative tumor border pattern and this was statistically significant (p<0.05). In addition, the overexpression of cdc2 was correlated with histologic high grade carcinomas (p=0.00).

Conclusion

Cyclin B1 and cdc2 appeared to be involved in the genesis or progression of breast cancers. In addition, the overexpressions of p16 and p53 may play important roles in more aggressive tumor and the overexpression of cdc2 is associated with progression of tumor to a higher grade of breast carcinomas. The deranged overexpressions of cyclin B1, cdc2, p16 and p53 may play an important role in human breast carcinogenesis.     

Overexpression of CyclinD1 and underexpression of p16 correlate with lymph node metastases in laryngeal squamous cell carcinoma in Chinese patients

Background CyclinD1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorgenesis of laryngeal squamous cell carcinoma (LSCC). Previous studies have examined the level of expression of cyclinD1 or p16 in LSCC but no such information is available for their relation and their correlation with lymph node metastasis in Chinese patients. Patients and methods A total of 58 patients underwent surgical resection of laryngeal tumours in the Department of Otolaryngology, Qilu Hospital Shandong University between January 2001 and December 2002. All pathologic specimens were available for immunohistochemical study using antibodies against cyclinD1 and p16. Results Compared with normal epithelium, expression of CyclinD1 in the LSCC was significantly higher (62.1% vs. 10.0%, P < 0.05), expression of p16 was significantly lower (48.3% vs. 90.0%, P < 0.05); CyclinD1 expression in LSCC was up-regulated in TNM classification (r _s = 0.409, P < 0.05) as well as with cervical lymph node metastases (r _s = 0.294, P < 0.05); p16 expression in LSCC was down-regulated with cervical lymph node metastases (r _s = −0.275, P < 0.05); negative significant correlation between p16 immunostaining and CyclinD1 was observed in LSCC (r _s = −0.331, P < 0.05). Conclusion There was a negative correlation between CyclinD1 expression and p16 expression in LSCC. The over-expression of CyclinD1 and the under-expression of p16 may play a significant role in the incidence and development of LSCC and may be important indicators for cervical lymph node metastases in Chinese patients of LSCC. Zhi-jie Fu and Zhi-yong Ma are contributed to this work equally.     

肾癌中cyclinD1和p27kip1的表达及其意义

目的探讨cyc lin D1、p27k ip1在普通型肾细胞癌(renal cell carc inom a,RCC)发生、发展中的作用。方法用半定量RT-PCR方法检测25例普通型RCC和10例肿瘤远端的正常肾组织中cyc lin D1的mRNA含量,用免疫组化方法检测76例普通型RCC中cyc lin D1和p27k ip1蛋白的表达,并对cyc lin D1、p27k ip1蛋白表达与临床病理参数的关系进行分析。结果普通型RCC中cyc lin D1的mRNA含量0.488±0.399,高于正常对照组0.089±0.066(P<0.01)。cyc lin D1的表达与肿瘤体积大小有关,体积大者cyc lin D1高表达(P<0.05)。普通型RCC中p27k ip1表达低于正常对照组,随着p27k ip1表达的降低,肿瘤的细胞核Fu-hrm an分级、TNM分期增高。结论cyc lin D1高表达和p27k ip1的低表达与普通型RCC的发生有关;p27k ip1的低表达可能促进肿瘤的演进,p27k ip1的表达可作为评价普通型RCC预后的参考指标。     

重组人内抑素对佐剂性关节炎大鼠滑膜组织p21、cyclin D1及CDK4表达的影响

目的 观察重组人内抑素(rhEndostatin)对佐剂性关节炎(AA)大鼠滑膜组织p21,细胞周期素D1(cyclin D1)及细胞周期素依赖性激酶4(CDK4)基因表达的影响,探讨rhEndostatin抑制AA大鼠成纤维样滑膜细胞(FLS)增殖的分子机制. 方法 雄性SD大鼠36只,随机分为正常组(n=12)、AA模型组(n=12)和rhEndostatin(2.5mg/kg)治疗组(n=12).制备AA大鼠模型,分别采用实时荧光定量PCR和Western blotting方法,定量分析rhEndostatin对AA大鼠滑膜组织p21、cyclin D1、CDK4 mRNA及cyclin D1蛋白表达的影响. 结果 rhEndostatin治疗组大鼠滑膜组织p21、cyclin D1 mRNA和cyclin D1蛋白表达水平降低,CDK4 mRNA表达水平增加,与AA模型组比较,差异均有统计学意义(P< 0.01). 结论 rhEndostatin降低AA大鼠滑膜组织 cyclin D1表达水平可能是其抑制AA FLS增殖的分子机制之一.     

乳腺浸润性导管癌中p57kip2、cyclin D1和cyclin E的表达及意义

目的探讨p57kip2、cyclin D1及cyclin E蛋白在乳腺癌发生、发展中作用.方法用免疫组化S-P法检测64例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)、15例乳腺导管原位癌(ductal carcinoma in situ,DCIS)和15例癌旁正常乳腺组织中p57kip2、cyclin D1和cyclin E蛋白的表达情况.结果p57kip2、cyclin D1和cyclin E蛋白在IDC的阳性率与在乳腺不同组织之间相比,cyclin D1、cyclin E蛋白在DCIS的阳性率与癌旁正常乳腺组织之间相比差异均有显著性(P≤0.05,P＜0.01).在IDC中,三者表达均与腋窝淋巴结转移有关(P≤0.05,P＜0.01),cyclin D1蛋白的表达与组织学分级有关(P＜0.01),cyclinE蛋白的表达与肿块大小有关(P＜0.01);p57kip2与cyclin D1之间、p57kip2与cyclin E之间的表达均呈负相关(P＜0.01)、cyclinD1与cyclin E之间的表达呈正相关(P＜0.01).结论p57kip2蛋白低表达、cyclin D1和cyclin E蛋白高表达可能是乳腺组织恶性转变以及乳腺癌发生淋巴结转移的重要生物学标志,cyclin D1和cyclin E蛋白异常表达是乳腺癌发生的早期事件.联合检测p57kip2、cyclin D1及cyclin E蛋白对预测乳腺癌淋巴结转移有重要意义.     

Reduced expression of the cell-cycle inhibitor p27Kip1 is associated with progression and lymph node metastasis of gastric carcinoma

AIMS: p27Kip1 (p27), a cyclin-dependent kinase inhibitor, plays an important role as inhibiting the progression of the cell cycle. Decreased expression of p27 is associated with high histological grade and aggressiveness of several human tumours. We aimed to evaluate the role of p27 in the progression and metastasis of gastric carcinoma. METHODS AND RESULTS: We analysed the expression of p27 in 67 primary gastric carcinomas and 31 lymph node metastases by immunohistochemistry. Reduced expression of p27 was found more frequently in advanced gastric cancer (40.9%) than in early gastric cancer (15.6%) (P < 0.001). Decreased p27 expression correlated with large tumour size, high histological grade, lymphatic invasion, advanced stage, deep invasion, lymph node metastasis and recurrence. The expression of p27 showed an inverse correlation with the Ki67 labelling index. There was a significant reduction of p27 expression in metastatic tumour cells in lymph nodes (mean positive cells: 3. 7%) when compared to the corresponding primary gastric carcinomas (mean positive cells: 8.1%) (P = 0.008). CONCLUSIONS: Alterations of p27 expression may play an important role in the progression and metastasis to lymph node of tumour cells in human gastric carcinoma.     

肺鳞癌和肺腺癌中Pin1与cyclin D1的表达及意义

目的探讨Pin1（the peptidy-proly1 isomerase）在肺鳞癌和肺腺癌组织中的表达及其与组织类型、肿瘤分化、分期及淋巴结转移关系,并分析其与细胞周期素（cycinD1）是否存在相关性。方法采用SP免疫组化方法检测69例肺鳞癌和肺腺癌组织中Pin1和cyclin D1的表达。结果免疫组化结果显示：Pin1与cyclinD1在肺鳞癌、肺腺癌中的阳性表达率分别为78．3％（54／69）、52．2％（36／69）。Pin1与cyclinD1在肺癌组织中的表达水平均高于正常肺组织。Pinl的表达与患者的性别、年龄、组织类型、分化、淋巴结转移与否等临床病理学参数无相关。cyclin D1的表达与分化程度负相关（P=0．0274）,而与患者的性别、年龄、组织类型、淋巴结转移与否等临床病理学参数无相关。Pin1和cyclin D1二者的表达呈正相关（P=0．0048）。结论在肺癌中,Pin1的表达高于正常肺组织,但与临床病理学参数无关,而与cyclin D1正相关。其对cyclin D1的影响可能是Pin1发挥作用的主要机制之一。     

p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma

p21^WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II+III) (P-0·017) and poor tubule formation (P-0·002), and was significantly less frequent in lobular carcinomas (P-0·0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1^CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P<0·001 …). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation. © 1998 John Wiley & Sons, Ltd.