Positive Expression Of Ki-67 Research Articles

A pilot study of low-dose CT perfusion imaging (LDCTPI) technology in patients with triple-negative breast cancer.

To investigate associations between the clinicopathologic features and CT perfusion parameters of triple-negative breast cancer (TNBC) and non-TNBC using low-dose computed tomography perfusion imaging (LDCTPI), and to find potential clinical applications in the prognosis assessment of TNBC. A total of 60 patients with breast cancer confirmed by pathological examination were studied prospectively using LDCTPI on a 64-slice spiral CT scanner. The acquired volume data were used for calculations, mapping, and analysis by using a tumor perfusion protocol in the CT perfusion software package to measure 2 parameters namely, blood flow (BF), and permeability surface (PS) area product. Patients were grouped into TNBC (n = 27) and non-TNBC (n = 33) subtypes. Associations between these two subtypes and clinicopathologic characteristics were evaluated by both univariate and multivariate logistic regression. CT perfusion parameters values were compared for clinicopathologic characteristics using independent 2-sample t test. TNBC displayed higher CT perfusion parameters values (BF: 57.56±10.94 vs 52.70±7.79 mL/100 g/min, p = 0.006; PS: 38.98±9.46 vs 33.39±8.07 mL/100 g/min, p = 0.001) than non-TNBC. In addition, breast cancer with poorly histologic grade or positive Ki-67 expression showed higher BF and PS values than those with well and moderately histologic grade or negative Ki-67 expression (p < 0.05). TNBC had poorer histologic grade (P = 0.032) and higher Ki-67 expression (P = 0.013) than non-TNBC. LDCTPI is a functional imaging technology from the perspective of hemodynamics with potential of clinical applications. The BF and PS values were higher in TNBC patient group than non-TNBC group. TNBC patients also have poorer clinicopathologic outcome.

Abstract 4902: Positive Ki-67 expression in post neoadjuvant chemotherapy (NAC) radical cystectomy samples are associated with lack of tumor downstaging and shorter overall survival (OS) in patients with muscle invasive bladder cancer (MIBC)

Abstract Background: We recently reported single institution data on tumor downstaging and survival outcomes of 332 patients who underwent platinum based NAC followed by radical cystectomy for MIBC [Peyton et al. JAMA Oncol. 2018]. High expression levels of cell proliferation marker Ki-67 are associated with poor outcomes in chemotherapy naïve bladder cancer. Androgen receptor (AR) expression is associated with resistance to cisplatin in bladder cancer cell line models. We therefore studied Ki-67 and AR expression in our cohort of post NAC radical cystectomy samples and correlated them with tumor downstaging and OS. Methods: Tissue microarrays (TMAs) were constructed from 130 post-NAC cystectomy samples and up to 5 cores were taken from each radical cystectomy sample. Matched lymph node metastases if present were included in TMAs. The expression of Ki-67 and AR were evaluated with immunohistochemistry and the average of the H score was used to represent each radical cystectomy sample and its matched lymph node metastasis. Results: The median survival of this cohort of 130 patients was 33.4 months (range: 1.13 -127 months). 40 patients (31%) had tumor downstaging and 21 patients (16%) achieved pathological complete response. Using a Cox regression model for OS, positive Ki-67 expression in post NAC radical cystectomy samples is associated with poorer overall survival (hazard ratio=2.412, 95% CI:1.076-5.408, p=0.033), independent of the pathological N stage. Positive Ki-67 was significantly associated with lack of tumor downstage in a multivariable logistic regression model (odds ratio=0.081, 95% CI:0.014-0.464, p=0.004) while adjusting for adjuvant chemotherapy and pathological complete response. No statistically significant associations between AR and OS or AR and tumor downstaging were observed in multivariable analysis. When AR expression is evaluated as a binary variable (AR+, AR-), post NAC AR- expression is significantly associated with tumor downstaging compared to post NAC AR+ samples (Fisher’s exact test, p=0.002). When stratified by sex, a trend towards better survival was observed in females (36 patients) compared to males (94 patients) (p=0.089). Post NAC AR- female patients also demonstrated a trend toward better survival (Log rank test, p=0.497) when compared to post NAC AR+ females. Conclusions: Positive Ki-67 expression in post NAC radical cystectomy sample is associated with poorer OS and lack of tumor downstaging. If confirmed by a larger data set, Ki-67 can serve as a biomarker to select MIBC patients for post cystectomy adjuvant therapy. Note: This abstract was not presented at the meeting. Citation Format: Selene Rubino, Youngchul Kim, Junmin Zhou, Charles Peyton, Scott Gilbert, Wade Sexton, Jingsong Zhang. Positive Ki-67 expression in post neoadjuvant chemotherapy (NAC) radical cystectomy samples are associated with lack of tumor downstaging and shorter overall survival (OS) in patients with muscle invasive bladder cancer (MIBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4902.

LncRNA LINC00668 promotes the progression of breast cancer by inhibiting apoptosis and accelerating cell cycle.

Objective: To elucidate how lncRNA 00668 (LINC00668) influences the development of breast cancer (BC).Materials and methods: Genome-wide expression profile of BC and paracancerous tissues were downloaded from The Cancer Genome Atlas (TCGA) and BC tissues and paracancerous tissues enrolled from our hospital for analyzing the expression level of LINC00668 and its correlation with prognosis. GSEA was conducted to analyze the potential functions of LINC00668. By transfection of sh-LINC00668 in BC cells, proliferation, apoptosis, cell cycle and colony formation of BC cells were accessed. Western blot was conducted to detect protein expressions of Ki-67, CDK4, Bcl-2, p21 and genes in AKT/mTOR pathways after LINC00668 knockdown in BC cells. Finally, tumor-bearing nude mice were administrated with BC cells. We compared the proliferative rate in mice with different administrations. Immunohistochemistry was carried out to access expression levels of Ki-67, CDK4, Bcl-2 and P21 in mice.Results: Both TCGA data and BC tissues harvested from our hospital indicated the higher expression of LINC00668 in BC tissues. LINC00668 expression was negatively correlated to prognosis of BC patients. GSEA pointed out that LINC00668 is enriched in regulations of cell cycle and apoptosis. By transfection of sh-LINC00668 in MDA-MB-231 and MDA-MB-436 cells, the proliferative and colony formation abilities of BC cells decreased. Besides, LINC00668 knockdown in BC cells induced apoptosis and arrested cell cycle. LINC00668 knockdown downregulated Ki-67, CDK4 and Bcl-2, but upregulated p21. The AKT/mTOR pathway was inhibited after LINC00668 silenced. In vivo experiments demonstrated the decreased proliferative rate in tumor-bearing mice administrated with sh-LINC00668 transfected BC cells. Consistently, immunohistochemical results showed lower positive expressions of Ki-67, CDK4 and Bcl-2, but higher positive expression of p21 in sh-LINC00668 group.Conclusion: LINC00668 is highly expressed in BC tissues and can promote the progression of BC by inhibiting apoptosis and accelerating cell cycle progression.

Prognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer.

The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct. Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations. Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P<0.001 and<0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and <0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P<0.0001 and 0.0009, and P<0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF-1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022). The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.

The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer.

PurposeWe previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC.Materials and MethodsWith tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9-negative/Ki-67–low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67–high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling.ResultsThe median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016).ConclusionThis study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Expressions of Topo IIα and Ki67 in breast cancer and its clinicopathologic features and prognosis.

Objective:Breast cancer is one of the most common malignant tumors in women, and its incidence in women has ranked the first place among all malignant cancers. The evolution of breast cancer which is highly heterogeneous is a complex biological process involving multiple factors, genes and stages. Therefore, studying the expression and interaction of related genes is of great significance to further revealing of the mechanism of the occurrence and development of breast cancer and reduction of its resistance to chemotherapy. The purpose of this study was to investigate expressions of Ki67 and Topoisomerase IIα (Topo IIα) in breast cancer tissues and to explore the relationship between expressions of Ki67 and Topo IIα and the pathological characteristics and prognosis of breast cancer.Methods:Tissues with pathological changes and peripheral normal breast tissues were collected from 66 patients who underwent breast cancer treatment. Ki67 and Topo IIα in the breast cancer tissues and normal breast tissues were detected using immunohistochemical method. The relationships of Ki67 and Topo IIα with general clinicopathologic features and prognosis were analyzed.Results:It was found that the positive expressions of Ki67 and Topo IIα in the breast cancer tissues were higher than those in the normal tissues; the positive expression rate of Ki67 was in a correlation with diameter of breast cancer and lymphatic metastasis (P<0.05); the positive expression rate of Topo IIα was in a correlation with clinical stage, diameter of cancer and lymphatic metastasis (P<0.05). Multi-factor logistic regression analysis suggested that lymphatic metastasis and clinical stage were the independent predictive factors for positive expression of Topo IIα and lymphatic metastasis was the independent predictive factor for positive expression of Ki-67. Breast cancer patients with negative Ki67 and Topo IIα had significantly higher local recurrence rate than those who had positive Ki67 and Topo IIα (P<0.05) after surgery. The median time to progression (TTP) of the patients with positive expression of Topo IIα was lower than that with negative expression (P<0.05). The median TTP of the patients with negative and positive expression of Ki67 had no significant difference (P>0.05).Conclusion:Topo IIα and Ki67 can be used for reflecting the proliferation activity of cancer cells and can affect the postoperative recurrence and survival time after surgery. They may be involved in the occurrence, development and metastasis of breast cancer. They are expected to be indicators in the prognosis prediction of breast cancer and potential treatment targets.

Mammaglobin-A, VEGFR3, and Ki67 in Human Breast Cancer Pathology and Five Year Survival.

Background/Methods:This study determines the co-expression of mammaglobin-A, vascular endothelial growth factor receptor-3 (VEGFR3) and Ki67 by immunohistochemistry (IHC) in tissue samples from 80 patients undergoing breast surgery (cancer or benign disease). The tissue expression was compared with the tumour histopathology and Kaplan Meier 5-year survival analysis was performed.Results:Positive breast tissue expression was observed in 53% samples for mammaglobin, 41% Ki67 and 65% VEGFR3 with a significant positive correlation between Ki67 and VEGFR3 co-expression. Ki67 and VEGFR3 expression correlated with the breast tumour grade and Ki67 expression also correlated with oestrogen receptor (ER) status. At 5 years post-operatively, 6/80 patients had died and 3 patients were alive but had cancer recurrence. High Ki67 expression significantly correlated with poor survival (disease-free and overall).Conclusions:In this study, VEGFR3 and Ki67 expression but not mammaglobin-A correlated with breast tumour pathology. Positive Ki67 expression was also associated with a poor 5-year survival outcome.

Knockdown of nucleophosmin 1 suppresses proliferation of triple-negative breast cancer cells through activating CDH1/Skp2/p27kip1 pathway.

BackgroundNPM1 is a multifunctional phosphoprotein that commutes between the cytoplasm and nucleus in cell cycle process, which appears to be actively involved in tumorigenesis. Herein, we sought to investigate the possible role and prognostic value of NPM1 in triple-negative breast cancer (TNBC).MethodsAn array of public databases, including bc-GenExMiner v4.0, GOBO, GEPIA, UAL-CAN, ONCOMINE database and Kaplan-Meier plotter, were used to investigate the expression feature and potential function of NPM1 in TNBC. Immunohistochemistry, immunofluorescence, proliferation and colony formation, flow cytometry and western-blotting assays were used to analyze and verify the function and relevant mechanism of NPM1 in TNBC tissues and cells.ResultsAccording to analysis from bc-GenExMiner, the expression level of NPM1 was significantly higher in basal-like subtypes than luminal-A, HER-2 or normal-like subtypes of breast cancer (P<0.0001). GOBO database analysis indicated that the expression of NPM1 in basal-A or basal-B was significantly higher than luminal-like breast cancer cells. Immunohistochemistry assay in 52 TNBC tissue samples showed that positive expression of Ki-67 was 93.5% in the high-NPM1-expression group and 66.7% in the low-NPM1-expression group, respectively (P=0.032). Proliferation and colony formation assays demonstrated that inhibition of NPM1 suppressed cell growth by approximately 2-fold and reduced the number of colonies by 3-4-fold in MDA-MB-231 and BT549 cells. Moreover, inhibition of NPM1 in MDA-MB-231 and BT549 cells increased the percentage of cells at G0/G1 phase and decreased the percentage of cells at both S and G2/M phase, as compared with control counterparts. Western-blotting results showed that down-regulation of NPM1 could elevate CDH1 and p27kip1 expression, while decrease Skp2 expression both in MDA-MB-231 and BT549 cells. In addition, high mRNA expression of NPM1 correlated with shorter RFS (HR=1.64, P=0.00013) and OS (HR=2.45, P=0.00034) in patients with TNBC.ConclusionsNPM1 is significantly high expressed basal-like/triple-negative breast cancer and is correlated with shorter RFS and OS in this subset of patients. Knockdown of NPM1 impairs the proliferative capacity of TNBC cells via activation of the CDH1/Skp2/p27kip1 pathway. Targeting NPM1 is a potential therapeutic strategy against TNBC.

Expression and clinical implication of proliferation cell nuclear antigen protein in gastric cancer

Objective To investigate the expression level and the clinical significance of proliferation cell nuclear antigen (Ki-67) in gastric adenocarcinomas (GA) tissues and paired non-neoplastic tissues. Methods The express of Ki-67 in 170 paired of gastric cancer and corresponding adjacent tissues was detected by immunohistochemistry, and the relationship of Ki-67 level with clinicopathogical factors was explored. Results The positive expression of Ki-67 in cancer tissues was 64.10% (109/170), significantly higher than 35.90% (61/170) in non-neoplastic tissues (P=0.000, the Wilcoxon test). The up-expression of Ki-67 was not significantly correlated with patients’ age (P=0.595), sex(P=0.824), differentiation grade (P=0.542), TNM stage (P=0.073), distant metastasis(P=0.530), the depth of invasion (P=0.150), tumor size (P=0.143) and tissue type (P=0.854), but obvious related with 5-years survival of patients (P=0.000) and lymphnode metastasis (P=0.006). Conclusion Ki-67 may play important roles in the development and progression of gastric carcinoma. Key words: Gastric adenocarcinomas; Proliferation cell nuclear antigen; Immunohistochemistry

Therapeutic Effect of Penta-acetyl Geniposide on Adjuvant-Induced Arthritis in Rats: Involvement of Inducing Synovial Apoptosis and Inhibiting NF-κB Signal Pathway

Previous studies demonstrated that penta-acetyl geniposide ((Ac)5GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide. This study was aimed to observe the potential effect of (Ac)5GP on adjuvant-induced arthritis (AIA) in rat and explore the involved mechanisms. Rat AIA was induced by complete Freund's adjuvant. (Ac)5GP (30, 60, 120mg/kg) was given to AIA rats by intragastric administration. Paw swelling, polyarthritis index, serum pro-inflammatory cytokines levels, histological assessments of ankle joint, and proteoglycan expression were respectively measured to evaluate the therapeutic effect of (Ac)5GP on rat AIA. Immunohistochemistry for Ki67 and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of (Ac)5GP on AIA synoviocytes in vivo. Protein levels of Bcl-2, Bax, caspase 3, IκBα, p-IκBα, and NF-κB p65 in synovial tissues were detected by Western blot. We found that (Ac)5GP treatment could suppress secondary hind paw swelling, reduce polyarthritis index, decrease TNF-α and IL-1β serum levels, attenuate pathological damage of ankle joint, and promote proteoglycans expression. (Ac)5GP treatment also could reduce Ki67 positive expression rate and raise the synovial apoptosis index in synovial tissues. Additionally, (Ac)5GP (120mg/kg) could significantly decrease Bcl-2 protein level, increase Bax and cleaved caspase 3 protein levels, and normalize the ratio of Bcl-2 to Bax. Moreover, (Ac)5GP (120mg/kg) could inhibit the degradation and phosphorylation of IκBα and reduce NF-κB p65 protein level in nuclear extracts. In conclusion, (Ac)5GP showed a potent anti-arthritic effect on AIA rats via inducing synovial apoptosis and inhibiting NF-κB activation in synovial tissues.

Relationship between expression of BRAFV600E and Ki67 protein and clinical pathologic characteristics of thyroid carcinoma

Objective To explore the relationship between BRAFV600E, Ki67 protein and thyroid carcinoma with different pathologic characteristics, thus to provide clinical evidence on early prognosis and personalized treatment in patients with thyroid carcinoma. Methods From January 2015 to January 2017, 76 patients diagnosed as papillary thyroid carcinoma(PTC), who treated in Yinzhou People's Hospital, were enrolled.Twenty cases with normal tumor-adjacent tissue after operation and 34 patients with non-PTC were also enrolled as control.All the patients enrolled were not treated with endocrine, chemical and radiotherapy.The expression of BRAFV600E and Ki67 protein was detected by immunohistochemical method, and the BRAFV600E and Ki67 expression and their correlation with different pathologic characteristic of thyroid carcinoma was analyzed by SPSS 18.0. Results The positive rate of BRAFV600E and Ki67 protein in 110 patients with thyroid carcinoma was 56.36%(62 cases) and 39.09%(43 cases), with the highest expression of BRAFV600E and the lowest expression of Ki67 in patients with PTC respectively.The expression of BRAFV600E and Ki67 protein was all negative in normal tumor-adjacent tissue.The positive expression of BRAFV600E and Ki67 in patients with PTC demonstrated significant difference in TNM stage, tumor side and lymphoid node metastasis(BRAFV600E: χ2=5.281, 9.771, 9.771, all P 0.05; Ki67: χ2=0.224, 0.518, 1.281, all P>0.05). Conclusion The detection of BRAFV600E and Ki67 is benefit on judging of innocent and malignant, the malignant degree of thyroid tissue.The high expression of BRAFV600E and Ki67 is benefit on differentiating PTC and early evaluation of prognosis. Key words: Thyroid neoplasms; Protein, BRAFV600E; Protein, Ki67

Positive PCNA and Ki-67 Expression in the Testis Correlates with Spermatogenesis Dysfunction in Fluoride-Treated Rats

The present study aimed to evaluate the effect of fluoride (F) on spermatogenesis in male rats. F- at 50 and 100mg/L was administered for 70days, after which the testicular and epididymis tissues were collected to observe the histopathological structure under a light microscope. The ultrastructure of the testis and sperm was also examined via transmission electron microscopy. The apoptosis of spermatogenic cells was measured through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of proliferation factors, namely, proliferating cell nuclear antigen (PCNA) and Ki-67, in the testicular and epididymis tissues, were assayed through immunohistochemistry. F- at 50 and 100mg/L significantly damaged the structure of the testis and epididymis, and the testis and sperm ultrastructure exhibited various changes, including mitochondrial swelling and vacuolization, and apsilated and raised sperm membrane. F treatment significantly increased spermatogenic cell apoptosis in the testis. PCNA (P < 0.01) and Ki-67 (P < 0.01) also presented positive expression in the testis. By comparison, no significant changes occurred in the epididymis. In summary, excessive F intake results in spermatogenesis dysfunction by damaging the testicular structure and inducing spermatogenic cell apoptosis in male rats. The positive expression level of PCNA and Ki-67 was a good response to spermatogenesis dysfunction.

Expression of Ki67and p53 Proteins in Hodgkin ׳s Lymphomas and Non Hodgkin׳s Lymphomapatients using immunohistochemistry

Background: Hodgkin’s lymphoma (HL) and Non-Hodgkin’s lymphoma( NHL) are characterized by a profound disturbance of the cell cycle and apoptosis regulation., Ki-67 and P53 expression has been shown to be associated with adverse clinical outcome in a variety of malignant hematological disorders, including HL and NHL. Aim: This study aimed to clarify Ki-67 expression level and its correlation with p53 expression in HL and NHL. Material and methods: total of 28 newly diagnosed HL and NHL patients were investigated for Ki-67 expression and its correlation to p53 expression by immunohistochemical technique. Results: Ki-67 expression was observed in 46.7 % of HL patients while 7.7% of NHL patients gave positive Ki-67 expression. A significant Association between thetype of lymphoma and Ki67 expression (p&lt;0.05) noticed. The histopathologcal type appeared to be 57.1% mixed cellularity and 37.5% of them showed positive Ki67 expression , while 42.9 % were intermediate grade and only 16.7 % showed positive Ki67 expression . There were no significant correlation between the histopathologcal type and Ki67 expression. only 4 ( 14.3 %) of the cases were p53 negative ,while the rest 24 cases were p53 positive ,and the majority ( 66.7% ) were within score 2 . Eight cases ( 28.6 %) were positive for Ki-67 and p53 , Ki-67 was negative in 71.4% cases , and four of them were negative for p53 and the rest 16 ( 80% )cases were p53 positive .A significant correlation was found between p53 and Ki-67 expression where( r=0.608,p=0.001) . conclusion : it is suggested that immunohistochemical studies of p53 and Ki-67 expression in tumor tissue including HL and NHL can help in monitoring of patients at risk, and the markers may aid in controlling the progression of lymphoma and detect the degree of aggressiveness of the disease to give suitable treatment and management of patients .

Spinal Peripheral Primitive Neuroectodermal Tumors: A Radiological Analysis of Ten Cases.

To summarize the imaging features of spinal peripheral primitive neuroectodermal tumor (spPNET) patients. The computed tomography and magnetic resonance imaging features of 10 spPNET patients, four men and six women, were retrospectively analyzed, and their clinicopathological data were reviewed. The mean age of the patients was 24.7 years (range, 3-44 years). Ten spPNET lesions were found in the ten patients, including six extradural and four intradural extramedullary lesions. Radiologically, spPNET typically presented as heterogeneous isointense lesions with a heterogeneously enhanced pattern. A "vault wall-like growth" pattern, a linear enhancement pattern, and vertebral bone involvement tended to be found in the extradural lesions, whereas a ring enhancement pattern was found in the extramedullary intradural lesions. Positive Ki-67 expression might be related to necrosis, bone destruction, and hemorrhage. A well-defined spinal mass showing isointensity/attenuation with heterogeneous enhancement accompanied by other imaging features may be suggestive of spPNET and should be added to the list of differential diagnosis.

Correlation Between Contrast-enhanced Ultrasound Characteristics (Qualitative and Quantitative) and Pathological Prognostic Factors in Breast Cancer.

Little is known about the correlation between contrast-enhanced ultrasound (CEUS) characteristics and pathological prognostic factors in breast cancer. The aim of this study was to explore the correlation between CEUS characteristics and pathological prognostic factors. A retrospective study with 34 malignant breast lesions was conducted. CEUS characteristics included qualitative characteristics (e.g. lesion's enhancement degree and order, internal lesion homogeneity etc.) and quantitative characteristics (e.g. peak intensity, time to peak etc.). Also, pathological prognostic factors were included (e.g. tumor grade, estrogen receptor status etc.). Blurred lesion margins were observed more often in tumors of high histological grade (p=0.01) and in estrogen receptor-negative tumors (p=0.049). Furthermore, perilesional enhancement was associated with positive Ki-67 expression (p=0.049), while heterogeneous internal sentinel lymph node enhancement was associated with malignant infiltration of the node (p=0.002). CEUS has the potential to provide a prevision of pathological prognostic factors in malignant breast lesions, helping in the better early patient management.

A retrospective, single‑center cohort study on 65�patients with primary retroperitoneal liposarcoma

Primary retroperitoneal liposarcoma (PRPLS) is the most common soft tissue malignancy of the retroperitoneum. To determine the pathological features and the curative effects of surgery in patients with PRPLS, and to elucidate key prognostic factors, the present study retrospectively analyzed the clinical cases of 65 patients with PRPLS. Immunohistochemical analysis demonstrated that vimentin and Ki-67 are better indicators for PRPLS immunohistochemical diagnosis compared with S-100 protein. S-100 protein was predominantly expressed in well-differentiated PRPLS. Positive expression of vimentin and Ki-67 were observed in almost all PRPLS samples, and Ki-67 exhibited a higher expression level in high-grade PRPLS. The level of Ki-67 expression was negatively correlated with disease-specific survival (DSS). Survival analysis revealed that the pathological subtype and histological grade were associated with DSS and local recurrence in the patients, whereas the tumor burden was associated with DSS but not local recurrence. In addition, complete tumor resection and contiguous organ resection were able to improve DSS. Microscopically positive margins did not affect DSS, whereas gross margins did. Multivariate analysis revealed that pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, and that histological grade was an independent factor for local recurrence. Patient sex and age at presentation were not independent factors associated with prognosis or local recurrence. Correlation analysis demonstrated that postoperative local recurrence significantly affected DSS, and local recurrence was the most common cause of mortality among patients. Histological grade was strongly associated with the invasion of adjacent organs but not with tumor burden. Furthermore, the tumor burden was not associated with recurrence or tumor invasion of adjacent organs. Ki-67 expression was associated with prognosis. Pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, while histological grade was an independent factor which affected tumor recurrence.

Reduced miR-125a levels associated with poor survival of patients with hepatocellular cancer.

MicroRNAs (miRNAs) serve an important role in tumorigenesis and development. Although a low expression of miR-125a in hepatocellular carcinoma (HCC) has been reported, the clinical significance remains unknown. In the current study, the data of Gene Expression Omnibus datasets was analyzed and significantly low expression of miR-125a in HCC was verified. Furthermore, the expression and clinical significance of miR-125a was investigated in 27 normal liver and 98 HCC tissue samples using reverse transcription-quantitative polymerase chain reaction analysis. The results demonstrated that the level of miR-125a expression was lower in HCC biopsies compared with that in normal liver tissues. Survival analysis established that miR-125a expression was negatively associated with the prognosis of HCC. Multivariate survival analysis demonstrated that patients with HCC with lowmiR-125a and Ki67-positive expression have shorter overall, and disease-free survival times. Altogether, the results of the current study provide the first evidence that reducedmiR-125a expression is associated with HCC progression and poor prognosis in patients, suggesting that miR-125a may have potential prognostic value as a tumor biomarker for patients with HCC.

Ki-67 protein predicts survival in oral squamous carcinoma cells: an immunohistochemical study.

The aim of this study was to identify the expression of Ki-67 and MCM3 in oral squamous cell carcinoma (OSCC) as well as to address the correlation with patient survival and clinical features. Samples were collected from 51 patients with OSCC who presented for follow-up. Immunohistochemical expression of Ki-67 and MCM3 in all groups was performed. The scoring system was previous published by Tsurutani in 2005. We used Kappa index to evaluate observers agreement degree. The associations between protein expression and clinical variables were examined for statistical significance using the chi-squared test. The overall survival rates were estimated by the Kaplan-Meier method and the relationship between protein expression and survival was compared using the log-rank test (p < 0.05). The overall survival time for a patient with positive immunostaining for Ki-67 is shorter than for a patient with negative immunostaining, (log-rank test, p = 0.00882). Patients with tumor size T3 and T4 showed a statistically significant relationship with Ki-67 immunoexpression (log-rank test, p = 0.0174). The relationship between Ki-67 expression and the relation between age, gender, smoking, tumor site, lymph node metastasis and disease stage was not significant. The examiners agreement degree by Kappa presented p value < 0.05. There was not a significant correlation when we evaluated MCM3 expression regarding clinical characteristics and survival rate. From these results, the present study suggests that positive Ki-67 expression found in OSCC patients may contribute to predict the survival in OSCC samples, as well as the relation between the protein and the tumor size.

Relationships of cyclin E with clinical outcome and biomarkers in older women with early operable primary breast cancer.

e12031 Background: Cyclin E is one of the factors responsible for transition from G1 to S phase of cell division. Cytoplasmic cyclin E has recently been shown to be associated with the greatest risk of breast cancer recurrence (Hunt KK et al. Clin Cancer Res. 2016 Nov 23). This study aimed to analyse intracellular relationships of cyclin E with clinical outcomes and with other biomarkers in a specific patient population. Methods: Over 37 years (1973-2010), 1,758 older (≥70 years) women with early operable (&lt;5cm) primary breast cancer were managed in a dedicated clinic in Nottingham. Of these 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray construction and immunohistochemical studies of biomarkers. Cytoplasmic expression of cyclin E with or without nuclear expression was considered positive. Results: Cytoplasmic cyclin E expression was associated with poor clinical outcomes on multivariate analysis (see table below). Cytoplasmic cyclin E expression was significantly associated with negative ER(&lt;0.001), PR(p=0.008), CK19(p=0.009) and positive expression of Ki67(p=0.04), p53(p=0.02), CK5(p=0.001), CK17(p=0.04), LKB1(p=0.04), HER3(p=0.03) and HER4(p=0.04). No correlation was found with HER2, BRCA2, CK5/6, CK18, EGFR, CD44, MDM2, MDM4, E-Cadherin and MUC1. Conclusions: Cytoplasmic cyclin E is associated with poor clinical outcome and biomarkers of poor prognostic significance in older population with breast cancer. Cyclin E may serve as a potential therapeutic target in future. [Table: see text]

Isolation and identification of senescent renal tubular epithelial cells using immunomagnetic beads based on DcR2

Cell senescence plays a major role in the progression of tumors and chronic conditions such as diabetes and chronic kidney disease. Senescent cells are an important model for the study of aging-related diseases, and there is currently no efficient method for sorting out senescent cells. Decoy receptor 2 (DcR2) is a transmembrane receptor of the tumor necrosis factor superfamily, which is specifically expressed in senescent cells. In this study, we used magnetic activated cell sorting (MACS) isolation of a highly-pure populations DcR2-positive renal tubular epithelial cells (RTECs) based on three senescent cell models including the fifth passage cells, advanced glycation end-products (AGEs)- and H2O2-induced cells. The percentages of DcR2 positive RTECs in G1 and S phases increased by 20% and 4%, respectively, as compared to that in the pre-sorted cells. The positivity rates of SA-β-gal, p16, and senescence-associated heterochromatin foci (SAHF) in DcR2-positive RTECs were about 40%, 30%, and 44% higher than that prior to cell sorting. The levels of IL-6 and TGF-β1 in the supernatant were increased by 1.7 and 1.5 folds, respectively, as compared to that observed prior to sorting. No significant cell death was observed after 5days of continuous culture. Ki-67 positive expression rate in DcR2 negative RTECs was significantly higher than that in DcR2 positive RTECs after MACS. We demonstrated the use of DcR2 to classify live, senescent RTECs with a high specificity and stability. Our findings lay the foundation for further study of senescent RTECs in the progression of chronic kidney disease.