胆管癌表皮生长因子受体,增殖细胞核抗原的表达

为研究胆管癌组织中表皮生长因子受体（ＥＧＦＲ）、增殖细胞核抗原（ＰＣＮＡ）的表达及其生物学意义，并探讨ＥＧＦＲ表达与血型Ａ抗原的关系，通过应用免疫组织化学方法（ＡＢＣ法）检测３０例肝外胆管癌。结果发现１５例（５０％）为ＥＧＦＲ阳性，ＰＣＮＡ阳性７例（２３．３３％），对照组５例为非肿瘤胆总管，ＥＧＦＲ、ＰＣＮＡ均为阴性。胆管癌与非肿瘤胆总管组ＥＧＦＲ及ＰＣＮＡ表达率有显著差异，细胞分化差、有胆管外转移的胆管癌ＥＧＦＲ的表达率高于细胞分化好、无胆管外转移病例。胆管癌各组间ＰＣＮＡ表达率均无显著性差异。ＥＧＦＲ表达与血型Ａ抗原无关。结果提示：检测ＥＧＦＲ表达是判断胆管癌增生活性的有效手段，而ＰＣＮＡ尚需进一步研究。     

增殖细胞核抗原在估计胆管癌预后的价值探讨

为探讨增殖细胞核抗原（ＰＣＮＡ）在估计胆客癌预后中价值，应用免疫组化方法研究胆管癌及其生病变ＰＣＮＡ蛋白的表达。结果显示：３０例胆管癌患者ＰＣＮＡ蛋白阳性表达率为８６．７％（２６／３０），有性病变组比较有显著性差异（Ｐ〈０．０１），表明癌有较强的细胞增殖活性。Ⅲ期胆管癌ＰＣＮＡ高增殖组（８例）平均生存期１３个月，低增殖组（１０例）为２６个月，两组有显著性差异（Ｐ〈０．０５）。提示ＰＣＮＡ对估计胆     

PCNA、T和Th淋巴细胞在肾透明细胞癌的表达与预后的关系

应用免疫组化方法检测增殖细胞核抗原（ＰＣＮＡ）、Ｔ淋巴细胞（Ｔ）和辅助Ｔ淋巴细胞（Ｔｈ）在５２例肾透明细胞癌中的阳性表达，分析其与预后的关系。结果：ＰＣＮＡ指数（ＰＣＮＡＬＩ）与肿瘤核分级存在相关性，与分期无关；ＰＣＮＡＬＩ≥２０％组的生存率明显低于＜２０％组（Ｐ＜０．０５）。Ｔ淋巴细胞标记指数（ＴＬＩ）≥１０％组生存率明显高于＜１０％组（Ｐ＜０．０５）；辅助Ｔ淋巴细胞标记指数（ＴｈＬＩ）≥１０％及ＴｈＬＩ＜１０％两组间生存率无显著性差异（Ｐ＞０．０５），ＴＬＩ、ＴｈＬＩ与肿瘤分期、核分级无相关性。结论：ＰＣＮＡＬＩ、ＴＬＩ可以作为肾透明细胞癌的预后指标，ＴｈＬＩ与预后无相关性     

睾丸生殖细胞肿瘤中p53与增殖细胞核抗原表达的关系

为探讨生殖细胞肿瘤的细胞增殖状态及ｐ５３蛋白阳性细胞与肿瘤病理特点的关系、细胞增殖与ｐ５３基因在生殖细胞肿瘤中表达的相互关系，本实验采用免疫组化的方法对１３例睾丸生殖细胞肿瘤石蜡切片进行增殖细胞核抗原（ＰＣＮＡ）、ｐ５３蛋白染色。结果显示，浸润性肿瘤组ＰＣＮＡ－ＬＩ显著高于非浸润性肿瘤组（Ｐ＜０．０５）；尽管精原细胞与非精原细胞瘤组ＰＣＮＡ－ＬＩ、ｐ５３表达无显著性差别，但后者的表达高于前者。非精原细胞瘤组中，ＰＣＮＡ－ＬＩ和ｐ５３的表达高度相关（ｒ＝０．６４）。实验结论是：ＰＣ－ＮＡ－ＬＩ和ｐ５３的表达与肿瘤的恶性程度呈正比，且二者表达正相关。     

前列腺癌增殖细胞核抗原的免疫组化研究

为了探讨增殖细胞核抗原（ＰＣＮＡ）与前列腺癌分化程度的关系及其对预后的影响，采用ＰＣＮＡ单克隆抗体及免疫组织化学链菌素－生物素标记法（ＬＳＡＢ法），对３８例前列腺癌穿刺的石蜡标本中ＰＣＮＡ的表达进行了检测，以１５例前列腺良性增生及１０例正常前列腺组织作为对照，通过观察、统计组织切片中ＰＣＮＡ表达阳性细胞数目，计算出ＰＣＮＡ表达的阳性指数。结果发现，在低分化癌、中分化癌、高分化癌、前列腺良性增生及正常前列腺组织中，其ＰＣＮＡ阳性指数依次为８．０±４．０％、５．２±１．８％、２．４±１．１％、１．１±０．３％、０．８±０．６％，呈逐渐降低趋势。３８例前列腺癌患者经去势手术后随访１年以上者２５例，其中死亡６例，死亡组ＰＣＮＡ表达平均指数为９．０±３．０％，非死亡组为５．０±４．２％。两组比较Ｐ＜０．０５。结果表明：ＰＣＮＡ是判断细胞增殖程度的重要指标，对估计前列腺癌的分化程度及推测预后具有重要参考价值。     

增殖细胞核抗原在肝硬化,肝细胞不典型增生和肝细胞癌中？…

目的 探讨肝细胞癌（ＨＣＣ）的分析状态与增殖细胞核抗原（ＰＣＮＡ）表达的关系。方法 采用ＰＡＰ酶标法半定量检测（ＰＣＮＡ）在１９例肝硬变、２１例肝细胞不典型增生（ＬＣＤ）和５４例ＨＣＣ中的标记指数（ＬＩ）。结果 ＰＣＮＡ主要定位于肝癌细胞中。在ＨＣＣⅠ级、Ⅱ级、Ⅲ级中ＰＣＮＡ的标记指数（ＬＩ）分别为２０．６％、４２．２％、６８．９％，均存在着显著性差异（Ｐ〈０．０１）；在肝硬变、ＬＣＤ中的ＬＩ分别     

膀胱移行细胞癌增殖细胞核抗原表达的研究

采用免疫组化ＬＳＡＢ法对４８例膀胱移行细胞癌增殖细胞核抗原（ＰＣＮＡ）进行检测，发现ＰＣＮＡ增殖指数随肿瘤分级的升高而增高，浸润生长肿瘤ＰＣＮＡ增殖指数明显高于乳头状生长者（Ｐ＜０．００１），ＰＣＮＡ高表达组（增殖指数＞５０％）预后明显差于ＰＣＮＡ低表达组（增殖指数≤５０％）。结果表明ＰＣＮＡ可作为膀胱移行细胞癌恶性程度及预后指标之一。     

增殖细胞核抗原和C－erbB－2基因产物P185蛋白在人类肾癌中表达的研究

应用增殖细胞核抗原（ＰＣＮＡ）和Ｐ１８５单克隆抗体，通过免疫组织化学方法检测５例正常肾组织和４５例肾癌组织中Ｃ－ｅｒｂＢ－２癌基因产物Ｐ１８５蛋白和ＰＣＮＡ的表达状况。结果：５例正常肾组织中未发现Ｐ１８５蛋白和ＰＣＮＡ阳性表达；４５例肾癌中Ｐ１８５蛋白和ＰＣＮＡ阳性表达率分别为８４．４％和４４．４％。表明阳性表达的Ｐ１８５蛋白和ＰＣＮＡ分别定位于肿瘤的细胞膜上和细胞核内；Ｐ１８５蛋白和ＰＣＮＡ阳性表达率与肾癌的病理分级、临床分期和患者术后生存期相关。提示Ｐ１８５蛋白和ＰＣＮＡ阳性表达在肾癌发生和发展中起着重要作用，可作为评价肾癌预后的新参数。     

乳癌增殖细胞核抗原表达在判断乳癌患者预后中的价值

目的 探讨乳癌增殖细胞核抗原（ＰＣＮＡ）表达的判断预后价值及其与常用预后指标的相关性。方法 采用免疫组织化学方法检测５７例乳癌的ＰＣＮＡ表达,并对此５７例进行了定期随访。结果 ５７例乳癌中,ＰＣＮＡ阳性者３５例（６１．４％）,阴性者２２例（３８．６％）,经中位时间为３２个月的随访,７例出现远处转移或死亡者均为ＰＣＮＡ阳性表达者。ＰＣＮＡ与腋淋巴结转移、组织学分级、转移或死亡率有显著相关（Ｐ〈０．０     

胆系恶性肿瘤增殖细胞核抗原表达及其意义

作者应用ＡＢＣ免疫组化法研究４０例胆囊癌和４２例胆管癌组织中增殖细胞核抗原（ＰＣＮＡ）表达及其意义。高分化和组织学分级Ｉ级的胆系癌ＰＣＮＡ阳性细胞率评分均数明显低于低分化或未分化和组织学分级ＩＩＩ组的胆系癌；转移组胆囊癌和胆管癌ＰＣＮＡ阳性细胞率评分均数明显高于未转移组病例，结果提示ＰＣＮＡ阳性细胞率高的胆囊癌和胆管癌预后不良，ＰＣＮＡ可能是反映胆囊癌和胆管癌生物学行为和预后的重要指标。     

Proliferating cell nuclear antigen in testes of infertile men with varicocele--preliminary results of interrelationship with sperm count before and after varicocelectomy

OBJECTIVE: This study was conducted to assess germ cell kinetics and correlate them with sperm counts before and after varicocelectomy. MATERIAL AND METHODS: Forty-three testicular biopsy specimens were obtained from 47 patients with varicocele during varicocelectomy. Similar specimens were obtained from 8 fertile volunteers. All specimens were immunostained using anti-proliferating cell nuclear antigen (anti-PCNA) antibody. PCNA expression was evaluated by assessing its staining intensity (SI) and labeling index (LI). RESULTS: The varicocele specimens revealed significantly lower SI and LI than the controls. There was a significant correlation between initial sperm concentration and LI but not SI. Coexistence of LI > or = 31 and preoperative sperm count > 1 million/ml correlated with a significant rise in the postoperative sperm count. CONCLUSIONS: PCNA is a useful molecular marker for assessing germ cell kinetics in varicocele patients. The decline in DNA synthesis, as suggested by the lower PCNA SI and LI in varicocele specimens, could be a reason for the disordered spermatogenesis in these patients. PCNA LI may also be considered as a beneficial clinical marker and may help to predict the surgical outcome after varicocele repair.     

胃肿瘤中增殖细胞核抗原表达的临床研究

为了解增殖细胞核抗原（ＰＣＮＡ）在胃肿瘤中的表达及春临床意义，应用免疫组化技术（ＡＢＣ法）对胃肿瘤（胃腺瘤性息肉１０例，胃癌９４例）组织切片中ＰＣＮＡ含量进行半定量检测，结果。（１）胃粘膜不同病理状态下ＰＣＮＡ指数差异有极显著性意义（Ｐ〈０．０１）；（２）ＰＣＮＡ指数与患者的性别和年龄无关（Ｐ〉０．０５），而与肿瘤的生长方式，组织类型，浆膜层受侵与否，淋巴结转移与否和临床分期关系密切（Ｐ〈０．０５     

Assessment of Proliferating Cell Nuclear Antigen Expression and Prognosis in Patients with Renal Cell Carcinoma with Pulmonary Metastases

Background: The presence of proliferating cell nuclear antigen (PCNA) has been suggested as a more important prognostic marker than either grade or mitotic in the prognosis of patients with renal cell carcinoma. We assessed the immunoreactivity of PCNA in primary lesions and pulmonary metastases from patietns with renal cell carcinoma and correlated the results with various histopathologic features and prognostic factors.
Methods: We studied the relationship between PCNA expression and clinical prognostic factors from resected primary lesions and pulmonary metastases from 10 patients and primary lesions from 32 patients with renal cell carcinoma without metastases. The cells were immunohistochemically stained with PCNA monoclonal antibody (PC-10) and 1000 nuclei were counted. The results were expressed as a ratio of stained to total cells (PCNA labeling index, LI |X%).
Results: The PCNA LI of pulmonary metastatic nuclei was significantly higher than the PCNA LI of renal lesions either from patients with (P < 0.05) or without (P < 0.01) metastases. Also, the mean PCNA LI of the pulmonary lesions in patients dying within 3 years of diagnosis was higher than the mean PCNA LI of patients surviving greater than 3 years.
Conclusion: Our findings suggest that the PCNA LI, which was determined by immunohistochemical analysis, is an important market reflecting the biologic behavior of renal cell carcinomas. The degree of PCNA expression in this study was of prognostic significance.     

Correlation of Nuclear Morphometry and Immunostaining for p53 and Proliferating Cell Nuclear Antigen in Transitional Cell Carcinoma of the Bladder

Background :
In an attempt to determine the biological significance of nuclear morphometric findings, measurements of mean nuclear volume (MNV) and nuclear roundness factor (NRF) were compared to the immunoreactivityof p53 expression and proliferating cell nuclear antigen (PCNA) in human bladder cancer.
Methods :
MNV and NRF were measured using stereological methods. Expression of p53 and PCNA were determined by immunohistochemical staining. Specimens from 111 patients with previously untreated bladder cancer were analyzed.
Results :
The mean MNV was 235.8 ± 1 33.6 μm³ for the 81 patients with p53-labeling index (LI) less than 10% and 337.2 ± 141.0 μn³ for the 30 patients with p53 LI greater than 10% (P = 0.008). There was Resign if icant correlation between NRF and expression of p53. The mean MNV was 220.1 ± 1 20.5 μm³ for the 67 patients with PCNA LI less than 28% (the mean value of PCNA LI) and 328.9 ± 149.2 μm³ in 44 patients with PCNA LI greater than 28% (P= 0.0001). The mean NRF was 80.7 ± 4.2 for the 67 patients with PCNA LI less than 28%, and 82.3 ± 3.4 for the 44 patients with PCNA LI more than 28% (P= 0.04). Conclusion: Nuclear morphometric findings may reflect the proliferative potential of cancer eel Is of the bladder, as indicated by findings of immunostaining for p53 and PCNA.     

Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients

We have performed a systematic review and meta-analysis of proliferation markers (Ki-67, mitotic index (MI), proliferating cell nuclear antigen (PCNA) and thymidine or bromodeoxyuridine labelling index (LI)) with respect to survival in early breast cancer. Eighty-five studies involving 32,825 patients were analysed. Ki-67 (43 studies, 15,790 patients), MI (20 studies, 7021 patients), and LI (11 studies, 7337 patients) were associated with significantly shorter overall and disease free survival, using results from univariate and multivariate analyses from the individual studies. PCNA (11 studies, 2677 patients) was associated with shorter overall survival by multivariate analysis only, because of lack of data. There was some evidence for publication bias, but all markers remained significant after allowing for this. Ki-67, MI, PCNA and LI are associated with worse survival outcomes in early breast cancer. However, whether these proliferation markers provide additional prognostic information to commonly used prognostic indices remains unclear.     

Expression of bcl-2, p53 oncoprotein, and proliferating cell nuclear antigen in renal cell carcinoma

OBJECTIVES: This study was designed to examine the immunohistochemical expression of bcl-2, p53, and proliferating cell nuclear antigen (PCNA) and the relation of this expression to clinicopathological characteristics and prognosis in renal cell carcinoma (RCC). METHODS: The expression of bcl-2, p53 protein, and PCNA was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 53 patients whose clinicopathological data had already become clear. RESULTS: The expression of the bcl-2 protein was recognized in 34 cases (64%); the expression of the p53 protein, however, was seen in only 1 case. Bcl-2 positivity was not associated with any pathological parameters or prognosis. If the percentage of PCNA-positive cancer cells as compared to the total amount of cancer cells was defined as a labeling index (LI), a high PCNA LI number correlated significantly with a high T category, high grade, venous invasion, and shortened survival. Among the conventional pathological parameters, the T category, nuclear grade, and venous invasion had the most significant effect on prognosis. A multivariate analysis in the parameters of PCNA, T category, nuclear grade, and venous invasion demonstrated that only nuclear grade had a significant effect on prognosis. CONCLUSIONS: The inhibitory effect of the bcl-2 gene on apoptosis related to tumor development is not clear, and the expression of the p53 protein is uncommon in RCC. PCNA seems to be a good objective and quantitative marker of the biological malignant potential in RCC, although the assessment of malignant potential in combination with conventional pathological parameters is indispensable.     

Measurement of PCNA labeling index in astrocytic tumors]

PCNA (proliferating cell nuclear antigen) is said to be present specifically in the nucleus of proliferating cells. The PCNA labeling index (PCNA LI) of astrocytic tumors was measured and compared with histological types or prognosis. The specimens from 44 patients were fixed in a 10% formalin solution, and embedded in paraffin. The 3 microns-sections were stained immunohistochemically with anti-PCNA monoclonal antibody (PCIO, Novocastra) using an ABC method. The percentage of PCNA-positive-cells was determined by counting 2000 cells, and identified as PCNA LI. All of the PCNA-positive-cells showed diffuse nucleoplasmic staining. The averages of PCNA LIs in each pathological type were calculated and evaluated statistically. Although differences in averages of PCNA LIs among pilocytic, gemistocytic, fibrillary astrocytoma were not significant, there was a significant difference between anaplastic astrocytoma and glioblastoma. The relationship between PCNA LIs and the prognoses for 43 patients was studied. Forty-three patients were classified into 3 groups (over 22%, 7 to less than 22%, and less than 7%) according to PCNA LIs. The survival data in the 3 groups were analyzed, and differed significantly in the survival rates. Furthermore, twenty-three patients of anaplastic astrocytoma and glioblastoma were classified into two groups (over 22% and less than 22%). Likewise, the two groups differed significantly. In summary, pathological type and prognosis were closely related to PCNA LI in astrocytic tumors. Therefore, we thought measurement of PCNA LI would make it more possible to analyze clinically the proliferating activity of astrocytic tumors, and to care for patients more effectively.     

大肠癌组织及其癌旁粘膜PCNA和AgNORs的检测及其临床意义

目的　探讨大肠癌组织及癌旁粘膜中增殖细胞核抗原 (PCNA)的表达和核仁区嗜银染色 (AgNORs)计数的临床意义。方法　采用免疫组织化学 (SP法 )和嗜银染色技术对 48例大肠癌组织及其癌旁粘膜和 1 0例正常大肠粘膜中PCNA和AgNORs进行检测。结果　大肠癌组织中PCNA标记指数 (PCNA LI)和AgNORs计数均显著高于癌旁 3cm和 6cm粘膜及正常粘膜 (P<0 .0 1 ) ,PCNA LI在DukesC期和D期显著高于DukesA期 (P<0 .0 5)。癌旁 3cm粘膜细胞AgNORs计数显著高于癌旁 6cm粘膜 (P<0 .0 1 )及正常粘膜细胞的AgNORs计数 (P<0 .0 5)。结论　大肠癌癌旁粘膜部分细胞增殖调节失控 ,提示癌旁粘膜是一种不稳定的癌前状态 ,可能与大肠癌术后复发有关     

Clinical validity of proliferating cell nuclear antigen as an objective marker for evaluating biologic features in patients with untreated prostate cancer

BACKGROUND: Although Gleason grading may be the most useful system for evaluating biological activity of untreated prostate cancer, lack of interobserver validity with Gleason scores (GS) is an unsolved issue. In this study, the proliferating cell nuclear antigen labeling index (PCNA LI) in untreated prostate cancer was investigated in order to clarify the usefulness of supplemental and objective markers for evaluating the biologic features of prostate cancer. METHODS: Sixty cases of prostate cancer were randomly selected from the cancer registry in Gunma University Hospital for this study. PCNA LI were evaluated using paraffin-embedded biopsy cores taken at diagnosis. Correlation of PCNA LI with the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels and age were evaluated. Cumulative rates of freedom from cause-specific death were also evaluated stratified by various clinicopathologic features, including PCNA LI using Kaplan-Meier analysis. RESULTS: Proliferating cell nuclear antigen labeling index was significantly higher in patients with PSA levels over 100 ng/mL, advanced clinical stage (>T4, N1 or M1 disease), higher Gleason grade or with a higher GS than in those with other clinicopathologic features. The 5-year cumulative rate of death from prostate cancer was significantly higher at 62% in patients with a PCNA LI of 20 or more than those with PCNA LI of less than 20, who accounted for 4%. CONCLUSIONS: Proliferating cell nuclear antigen labeling index in combination with Gleason grading system may be of clinical value in evaluating biologic features and also in predicting cause specific survival of prostate cancer in an objective, reliable and reproducible manner.     

Proliferating-cell nuclear antigen (PCNA) as an independent prognostic marker in patients after prostatectomy: a comparison of PCNA and Ki-67

OBJECTIVE: To investigate the prognostic value of prostatic tumour cell proliferation, as measured by Ki-67 and proliferating cell nuclear antigen (PCNA), and to compare these measures in men at low and high risk for progression of tumour. PATIENTS AND METHODS: Two groups of patients with prostate cancer, i.e. 'metastatic' (M, 22) who had pT3b-4aN0M0 and pTanyN1M0, and 'nonmetastatic' (NM, 18), who had < or =pT3aN0M0 disease, were selected from a well-examined and mapped group of 114 treated by radical prostatectomy. Patients in the NM group were selected by the criteria of having a Gleason score of < or = 7. To assess proliferation, 1000 cells were counted at x 400 magnification by two observers and the percentage of tumour cells positively stained with Ki-67 and PCNA defined as the Ki-67 and PCNA labelling index (LI), respectively. The two LI were compared in the NM and M groups, and the correlation of the LIs with pathological stage, progression and prostate-specific antigen (PSA)-free survival evaluated. Prognostic values of the LI were analysed using multivariate analysis. RESULTS: The mean (range) follow-up was 33 (4-78) months. The mean LIs were higher in the M than the NM group for both PCNA and Ki-67 (P = 0.02 and 0.019, respectively). Both LIs were markedly different between the groups when stratified by progression, with both significantly higher in men with progression in the NM group. Both LIs had a significant association with Gleason score, pathological stage, progression and PSA-free survival. In multivariate analysis the PCNA LI, surgical margin status and pathological stage were independent factors for progression. CONCLUSION: Tumour cell proliferation as assessed by Ki-67 or PCNA correlate significantly with progression. The PCNA LI was an independent predictor of progression, especially in patients with a low risk of progression according to predefined criteria.