Expression of p120, Ki-67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value

The cell proliferation markers p120, Ki-67 and proliferating cell nuclear antigen (PCNA) recognize nuclear antigens. The expression of these proteins by immunostaining methods was reported to be of value in determining the prognosis of patients with malignant diseases. In this study, we evaluated the prognostic significance of the expression of nuclear antigens p120, PCNA and Ki-67 in prostate cancer and compared the results with other prognostic factors. Imprint smear samples obtained from 70 patients immediately after radical prostatectomy for prostatic carcinoma were immunostained with monoclonal antibodies against p120, Ki-67 and PCNA. The immunostaining results were correlated with Gleason score, tumour differentiation, stage and prostatic specific antigen (PSA) levels. Our findings demonstrate that p120, Ki-67 and PCNA expression in prostatic carcinoma smears, correlated significantly with the degree of Gleason score (P < 0.001). When combining p120, Ki-67 and PCNA positivity with tumour differentiation there was a significant association among these parameters (P < 0.001). Overexpression of p120, Ki-67 and PCNA, was also associated with increased PSA serum levels (>4 ng/ml) (P < 0.001). The distribution of p120, Ki-67 and PCNA expression in prostate carcinomas was not statistically significant for Ki-67 (P = 0.69) and p120 (P = 0.22) but was significant for PCNA (P < 0.001) as far as the histological stage (T2a, T2b, T2c, T3a). P120, Ki-67 and PCNA expression had significant prognostic value for disease-free survival. Our results conclude that nuclear antigens p120, Ki-67 and PCNA appear to be additional markers in the field of prognosis of prostatic carcinoma.     

鼻咽癌组织ki67表达与外周血NK细胞的关系及意义

目的：研究鼻咽癌组织Ki67的表达及外周血NK细胞水平的意义。方法：检测66例鼻咽癌组织Ki67水平及与外周血NK细胞的百分含量。结果：Ki67表达阳性率为96．97％,与临床分期有关（r=0．290,P=0．030〈0．05）,与淋巴结转移状态相关性在统计学上无意义（r=0．068,P=0．412〉0．05）;放疗前中后鼻咽癌外周NK细胞水平差别均有统计学意义（前中、中后、前后F=0．513,0．627,0．623,P分别为0．005,0．004,0．000,均〈0．05）;ki67的表达与放疗后NK细胞NK值负相关（r=-0．433,P=0．017〈0．05）。结论：Ki67的表达可能与临床分期有关,可能与放疗后NK值有关;Ki67表达与外周血NK细胞水平可以提示鼻咽癌组织增殖活跃程度和机体防御系统的状态.     

COX-2、Ki-67和结核菌L型感染在前列腺癌中的表达

目的探讨环氧合酶-2（COX-2）和Ki-67在前列腺癌中的表达以及结核菌L型感染率及临床意义。方法应用免疫组化、原位杂交和抗酸染色等方法检测了65例前列腺癌（carcinoma of prostate,PCa）和30例良性前列腺增生（benign prostatic hyperplasia,BPH）中的COX-2、Ki-67蛋白及mRNA的表达,以及结核菌L型的检出率;并对前列腺肿瘤主要临床资料和病理分级参数进行比较,用χ^2检验进行统计学处理。结果COX-2、Ki-67蛋白及mRNA阳性表达和结核菌L型检出率,前列腺癌明显高于前列腺增生（P〈0.001～0.05）。COX-2、Ki-67蛋白及mRNA阳性表达和结核菌L型检出率与前列腺癌的临床分期、病理分级有明显差异（P〈0.01～0.05）。淋巴结转移组中COX-2、Ki-67蛋白及mRNA的阳性表达率明显高于非转移组（P〈0.01）。结核菌L型检出率淋巴结转移组明显高于非转移组（P〈0.05）。结论COX-2、Ki-67蛋白及mRNA在前列腺肿瘤中不同程度异常表达以及结核菌L型检出率与肿瘤的临床分期、病理分级和转移呈正相关,提示2种基因均可作为判断前列腺癌生物学行为及患者预后参考指标。结核菌L型感染极有可能导致基因的变异或过表达,成为诱发肿瘤因素之一,它们可能有协同致瘤作用。     

EGFR和Ki-67在胶质瘤中表达的研究进展

胶质瘤是颅内常见的原发恶性肿瘤,而某些癌基因的激活、过表达或扩增、重排导致脑胶质瘤的形成。主要讨论脑胶质瘤的生物学特点,指出当前研究某些与肿瘤增殖活性及侵袭能力相关的基因改变、蛋白表达,推测其增殖和侵袭活动的具体过程,这是攻克脑胶质瘤的基础和关键。在众多与肿瘤相关的蛋白和基因中,选择了主要反映脑胶质瘤增殖活性和侵袭能力的相关基因——EGFR、Ki-67进行综述。从分子生物学水平评估脑胶质瘤细胞增殖和侵袭状态,在分析和判断胶质瘤的生长、分化程度,指导治疗方案的选择及预后的判断等方面有着重要的实用价值;但对于患者的预后,还需结合年龄、肿瘤位置、病理分级以及其他标记物等进行综合评价。     

鼻咽癌组织ki67 表达与外周血NK 细胞的关系及意义

目的:研究鼻咽癌组织Ki67的表达及外周血NK细胞水平的意义。方法:检测66例鼻咽癌组织Ki67水平及与外周血NK细胞的百分含量。结果:Ki67表达阳性率为96.97%,与临床分期有关(r=0.290,P=0.030<0.05),与淋巴结转移状态相关性在统计学上无意义(r=0.068,P=0.412>0.05);放疗前中后鼻咽癌外周NK细胞水平差别均有统计学意义(前中、中后、前后F=0.513,0.627,0.623,P分别为0.005,0.004,0.000,均<0.05);ki67的表达与放疗后NK细胞NK值负相关(r=-0.433,P=0.017<0.05)。结论:Ki67的表达可能与临床分期有关,可能与放疗后NK值有关;Ki67表达与外周血NK细胞水平可以提示鼻咽癌组织增殖活跃程度和机体防御系统的状态。     

Assessment of Ki-67 as a potential biomarker in patients with breast cancer

Breast cancer is the most common cancer in females, it accounts for one third of all malignancies affecting women. Appropriate biomarkers play significant role in predicting the prognosis and decide the specific therapy to each patient. In this study we aimed at evaluating the value of Ki-67 as a prognostic marker in breast cancer patients and to analyze the associations between Ki-67 and their clinicopathological parameters. This study included 92 patients with developed non metastatic breast cancer and 10 women had benign breast tumor served as controls. We measured the serum level by ELISA technique and tissue expression of Ki-67 by immunohistochemical technique. Our results showed that there were no statistically significant differences in serum Ki-67 levels between the two studied groups. As for Ki-67expression in breast cancer cells, the score increases with increase of tumor size, grade, premenopausal, Ki-67 expression in estrogen and progesterone receptor positive tumors showed lower values than estrogen and progesterone negative tumors, while higher Ki-67 expression was more frequently associated with HER2-positive. In conclusion; our study supports the finding that tissue Ki-67 expression may add prognostic information to that obtained from classical prognostic factors and can provide data of significant value to other important prognostic indicators such as pathological grading, and axillary lymph node involvement.     

Prognostic and predictive significance of p53, EGFr,Ki-67 in larynx preservation treatment

Background

The optimal management of advanced laryngeal and hypopharyngeal cancers (L&HC) must involve consideration of both survival and functional effect of the given treatment approach. Despite over two decades of investigations of several treatment options, including surgery, radiotherapy, chemotherapy or some combinations thereof, little consensus exists as to which treatment offers the best survival, together with functional speech and swallowing.

Aim

To determine predictive and prognostic value of p53, EGFr, Ki-67 in patients with advanced laryngeal and hypopharyngeal cancer, treated with larynx preservation intent.

Materials and methods

Thirty-three patients received 2–3 cycles of induction chemotherapy (ICHT) consisting of cisplatin and fluoruracil and underwent subsequent radical radiotherapy. Immunohistochemical analyzes of p53, EGFr and Ki-67 were performed.

Results

Response to ICHT was obtained in 24 patients (75%). Better response to ICHT was correlated only with EGFr expression (p = 0.04, RR = 1.91). The 5-year loco-regional control (LRC) and disease-specific survival (DSS) rates were 48% and 57%, respectively. The 5-year larynx preservation rate was 68% in responders to ICHT compared to 21% in non-responders (p = 0.02). It was also higher in patients without EGFr expression (but not significantly, p = 0.43).

Conclusion

Lack of EGFr expression is a favorable predictive factor for response to ICHT. Neither p53 nor Ki-67 have predictive and prognostic value in larynx preservation treatment.     

PCNA、Ki67 在胰腺疾病中的研究进展

PCNA、Ki-67是与细胞增殖有关的核抗原,在增殖的组织细胞中呈阳性表达,反映组织细胞的增殖活性,是细胞增殖的重要标记物。PCNA、Ki-67在正常发育的胚胎组织、糖尿病、胰腺肿瘤、胰岛移植等胰腺疾病及其他疾病中均高表达,同时也与其他系统肿瘤和疾病密切相关。PCNA、Ki-67作为增殖指标可以用于评价胰腺疾病、胰岛细胞移植后细胞再生数量及其他疾病的诊断、治疗及判断预后。目前已将它们视为细胞的标志物,用于细胞增殖的动力学研究,在临床病理上具有很大的应用前景。未来PCNA、Ki67将广泛应用于临床及基础研究,尤其用于研究胰腺疾病的新靶点、探索糖尿病的发病机制,对疾病的预防和治疗及胰岛移植具有一定的应用前景及意义。     

Runx3、Ki-67在宫颈病变中的研究进展

宫颈癌严重威胁女性健康和安全,是导致女性死亡的主要恶性肿瘤之一。近年来我国宫颈癌的发病率正以每年2%-3%的速度增长,因此早期诊断对于预防和治疗宫颈癌具有决定性的意义。Runx3基因是一个新近发现的肿瘤抑制基因,其低表达与多种恶性肿瘤的发生发展有关。Ki-67抗原是一种贯穿表达于增殖期细胞中的核抗原,其指数可以准确反映细胞的增殖情况。研究表明Runx3及Ki-67的表达与宫颈癌的发生发展密切相关。目前宫颈癌筛查中的细胞学检查及hr-HPV检测方法都具有一定的局限性,寻求新的筛查方法已成为研究热点。本文将对Runx3及Ki-67在宫颈癌中的研究进展做一综述。     

Knockdown of Ki-67 by small interfering RNA leads to inhibition of proliferation and induction of apoptosis in human renal carcinoma cells

To investigate the effect of small-interfering RNA (siRNA) targeted against Ki-67, which is an attractive molecular target for cancer therapy, on inhibiting Ki-67 expression and cell proliferation in human renal carcinoma cells (HRCCs), siRNAs were used to inhibit the expression of Ki-67 in HRCCs. Ki-67 mRNA levels were detected by RT-PCR and in situ hybridization analysis. Ki-67 protein levels were detected by Western blot and immunocytochemistry analysis. TUNEL assay was used to measure the apoptosis of carcinoma cells. Results of RT-PCR and in situ hybridization demonstrated reduction of Ki-67 mRNA expression in Ki-67 siRNAs treated 786-0 cells. Similar reduction in Ki-67 protein measured by Western blot and immunocytochemistry was observed in cells transfected with Ki-67 siRNA. Ki-67-siRNA treatment of HRCCs resulted in specific inhibition of proliferation and increased apoptotic cell death. From these findings we conclude that inhibition of Ki-67 expression by siRNA may be a reasonable approach in renal cancer therapy.     

The intrinsically disorderly story of Ki-67

Ki-67 is one of the most famous marker proteins used by histologists to identify proliferating cells. Indeed, over 30 000 articles referring to Ki-67 are listed on PubMed. Here, we review some of the current literature regarding the protein. Despite its clinical importance, our knowledge of the molecular biology and biochemistry of Ki-67 is far from complete, and its exact molecular function(s) remain enigmatic. Furthermore, reports describing Ki-67 function are often contradictory, and it has only recently become clear that this proliferation marker is itself dispensable for cell proliferation. We discuss the unusual organization of the protein and its mRNA and how they relate to various models for its function. In particular, we focus on ways in which the intrinsically disordered structure of Ki-67 might aid in the assembly of the still-mysterious mitotic chromosome periphery compartment by controlling liquid–liquid phase separation of nucleolar proteins and RNAs.     

The Ki-67 protein: fascinating forms and an unknown function

The Ki-67 protein is a nuclear and nucleolar protein, which is tightly associated with somatic cell proliferation. Antibodies raised against the human Ki-67 protein paved the way for the immunohistological assessment of cell proliferation, particularly useful in numerous studies on the prognostic value of cell growth in clinical samples of human neoplasms. The primary structure revealed potential phosphorylation site for a range of essential kinases, PEST sequences, and a forkhead-associated domain, which are features present in a variety of cell-cycle-regulating proteins, but information about the position of the Ki-67 protein within the protein network that drives the cell cycle remained scarce. There is now evidence that posttranslational modifications based on phosphorylation by cdc2 kinase and PKC accompany the remarkable redistribution of the Ki-67 protein from the interior of the nucleus to the perichromosomal layer during mitosis and vice versa. The discovery of Ki-67 equivalents in other species is advantageous for a precise and cross-species investigation of the structural requirements for its yet unknown function. The recently published data add new pieces to the challenging puzzle of this multifaceted protein, which are waiting to be put together.     

Prognostic value of miR-142 in solid tumors: a meta-analysis

Several studies on the prognostic value of microRNA 142 (miR-142) in solid tumors have reported conflicting results. Therefore, the aim of this meta-analysis was to evaluate the relationship between the miR-142 and prognosis in solid tumors. A comprehensive search for relevant studies was conducted until 10 November 2020. Studies that investigated the prognostic significance of the miR-142 in solid tumors were included. The hazard ratio and 95% confidence interval were calculated using a random-effects model. All data analyses were performed using the STATA 12.0 software (Stata Corporation, College Station, TX, U.S.A.). Twenty articles involving 2451 participants were included in the meta-analysis. The results showed that high miR-142 expression was a better predictor of overall survival (OS) (HR = 0.66, 95% CI: 0.47–0.93) and disease-free/progression-free/recurrence-free survival (DFS/PFS/RFS) (HR = 0.71, 95% CI: 0.55–0.91) compared with low miR-142 expression. MiR-142 can be used as an effective prognostic marker for patients with solid tumors. Future large prospective studies are warranted to further confirm the present findings.     

Prognostic significance of the systemic immune‐inflammation index in pancreatic carcinoma patients: a meta-analysis

Background: Systemic immune-inflammation index (SII) is a prognostic indicator for several malignancies, including pancreatic carcinoma; however, there is no consensus on its significance. In the current study, a systematic meta-analysis was used to explore the correlation between SII and prognosis in pancreatic carcinoma patients.Methods: PubMed, Embase and Cochrane Library databases were screened from inception to May 2020. Studies describing the prognostic role of SII in pancreatic carcinoma were then retrieved. The pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated using random- or fixed-effects models to determine the correlation between SII and prognosis.Results: A total of four studies, comprising 1749 patients, met the inclusion criteria of the study and were therefore included in this meta-analysis. The meta-analysis showed that high SII indicated was correlated with worse overall survival (OS) in patients with pancreatic carcinoma (HR: 1.43, 95% CI: 1.24–1.65, P<0.001). These findings were validated through subgroup analyses, stratified by the American Joint Committee on Cancer (AJCC) stage. In addition, patients with high SII showed poorer cancer-specific survival (HR: 2.32, 95% CI: 1.55–3.48, P<0.001). However, analysis showed no significant correlations between SII and disease-free and relapse-free survival (RFS).Conclusion: These findings indicate that SII is a potential non-invasive and a promising tool for predicting clinical outcomes of pancreatic carcinoma patients. However, the current research did not explore whether neoadjuvant therapy has an effect on the prognostic value of SII. Further studies using adequate designs and larger sample sizes are required to validate these findings.     

金葡菌L型感染致小鼠肿瘤中Survivin、Ki-67的表达及意义

目的探讨金黄色葡萄球菌(金葡菌)L型感染C57小鼠致瘤后,凋亡蛋白抑制因子(Survivin)和增殖细胞核相关抗原(Ki-67)在小鼠肿瘤及癌前病变中的表达及相关性研究。方法动物实验观察金葡菌L型感染90只C57小鼠后11.1%(10/90)小鼠发生肿瘤,14.4%(13/90)小鼠引起癌前病变。革兰染色、免疫组化及原位杂交检测小鼠肿瘤和癌前病变中金葡菌L型检出率和Survivin、Ki-67蛋白及cDNA的表达。结果10只小鼠肿瘤及13只小鼠癌前病变中金葡菌L型检出率及其cDNA阳性表达与正常对照组差异有非常显著性(P0.005~0.01);Survivin、Ki-67蛋白和cDNA的阳性表达与正常对照组差异有显著性(P0.01~0.05),呈正相关。结论金葡菌L型感染可能与Survivin、Ki-67基因协同在小鼠肿瘤发生和发展中起重要作用。     

Tumor Cell Identification in Ki-67 Images on Deep Learning

The proportion of cells staining for the nuclear antigen Ki-67 is an important predictive indicator for assessment of tumor cell proliferation and growth in routine pathological investigation. Instead of traditional scoring methods based on the experience of a trained laboratory scientist, deep learning approach can be automatically used to analyze the expression of Ki-67 as well. Deep learning based on convolutional neural networks (CNN) for image classification and single shot multibox detector (SSD) for object detection are used to investigate the expression of Ki-67 for assessment of biopsies from patients with breast cancer in this study. The results focus on estimating the probability heatmap of tumor cells using CNN with accuracy of 98% and detecting the tumor cells using SSD with accuracy of 90%. This deep learning framework will provide an objective basis for the malignant degree of breast tumors and be beneficial to the pathologists for fast and efficiently Ki-67 scoring.     

三阴性乳腺癌中Ki-67 的表达及其临床病理意义

目的:探讨三阴性乳腺癌中Ki-67的表达及其临床病理意义。方法:回顾性分析2010年11月1日至2015年12月31日辽宁省肿瘤医院收治的110例行乳腺癌根治术的三阴性乳腺癌患者的临床病理资料,检测其乳腺癌组织中Ki-67的表达,并分析其与患者年龄、绝经情况、组织学分型、临床分期、淋巴结转移、肿瘤大小等临床病理资料的关系。进一步采用Kaplan-Meier生存分析法绘制生存曲线,比较高表达Ki-67和低表达Ki-67患者的3年、5年生存率。结果:Ki-67在三阴性乳腺癌患者50岁以下和50岁以上相比较,差异具有统计学意义(P0.05);Ki-67在三阴性乳腺癌患者绝经情况、组织学分型、临床分期、淋巴结转移、肿瘤大小的表达相比较,差异不具有统计学意义(P0.05);高表达Ki-67组3年生存率为79.49%,5年生存率为30.77%;低Ki-67组的3年生存率为85.92%,5年生存率为46.48%;两组3年生存率相比较差异不具有统计学意义(P0.05);两组5年生存率相比较差异具有统计学意义(P0.05);两组总生存时间相比较,差异具有统计学意义(P0.05)。结论:三阴性乳腺癌中Ki-67呈高表达,可作为乳腺癌预后不良的危险因素。     

Cell cycle dependent distribution of the proliferation-associated Ki-67 antigen in human embryonic lung cells

The cell cycle-dependent distribution of the proliferation-associated Ki-67 antigen has been evaluated immunocytochemically in L-132 human fetal lung cells. The cells were synchronized and cell cycle phases were determined: G1 = 6.7 h, S = 5.4 h, G2 = 8.5 h and mitosis = 1.3 h. The Ki-67 patterns were strictly correlated with the cell cycle phases. In late G1-phase, Ki-67 antigen was present only in the perinucleolar region. In the S-phase, Ki-67 staining was found homogeneously in the karyoplasm and in the perinucleolar region. G2-phase cells contained a finely granular Ki-67 staining in the karyoplasm with Ki-67-positive specks and perinucleolar staining. In early mitotic cells (pro- and metaphase) an intense perichromosomal Ki-67 staining was observed in addition to a homogeneously stained karyoplasm in prophase, and cytoplasm in metaphase. During ana- and telophase the Ki-67 antigen disappeared rapidly. In resting cells there was no Ki-67 staining.     

胃癌组织中Tenascin、MVD、Ki-67的表达及其临床意义

目的：探讨胃癌组织中Tenascin蛋白、微血管密度（microvascular density,MVD）、Ki-67的表达及其与临床病理特征的关系。方法：采用免疫组化Elivision法检测70例胃癌组织和20例癌旁正常组织中Tenascin、CD34和Ki-67的表达。结果：①正常胃黏膜上皮Tenascin阴性,胃癌中的Tenascin主要表达于肿瘤相关纤维母细胞的胞质中,且与胃癌的Lauren分型、分化程度、临床分期、淋巴结转移显著相关（P〈0．05）;②胃癌中MVD和Ki-67-LI（标记指数）均高于正常胃黏膜（P〈0．001）,且均与胃癌的临床分期、浸润深度、淋巴结转移显著相关（P〈0．05）;结论：胃癌组织中Tenascin可抑制胃癌的演进,MVD及Ki-67可作为胃癌患者预后的预测指标,联合检测胃癌组织Tenascin、MVD、Ki-67的表达情况,对于进一步了解胃癌的生物学行为和判断预后具有一定的临床价值与意义。