Ki-67 Overexpression Research Articles

Potential Role for a Panel of Immunohistochemical Markers in the Management of Endometrial Carcinoma

BackgroundIn order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC. MethodsWe examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis. ResultsThe mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012). ConclusionsThe over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.

Prognostic importance of immunologochemical markers of papillary thyroid cancer

In Papillary Thyroid Cancer (PTC) in recent years an immunohistochemical markers were detected. Several authors consider their use as perspective to predict tumor behavior and the risk of recurrence and for differential diagnosis between different variants of PTC. However, the data obtained during various studies are controversial, which necessitates further research. Materials and methods: Using standard methods, the pathogistological material was obtained after surgical treatment of 273 patients with PTC. Expression of immunohistochemical markers: TTF1 and Gal3 - in 48 patients, p53 - in 50 patients, Ki-67 in 53 patients, NIS in 44 patients detected immunohistochemically. The connection between the histological type of tumor, the level of expression of immunohistochemical markers and the histological signs of aggressive tumor behavior are analyzed: multifocal, capsule invasion, extratireoidal invasion, lymph node damage. Results: In the analysis of data obtained with the use of standard histological techniques, it was found that the most aggressive variant was cylindrical cells PTC with a high incidence of extrathyroid invasion - 5.4 %, a capsule invasion -7.2 %, multifocal growth - 10.8 %, metastatic lymph nodes – 17.1 %. The high levels of TTF1 and Ki-67 expression, as well as the absence of NIS expression, were reliably associated with metastatic lymph node involvement (p <0.05). Reliable relationship with other histological signs of aggressive behavior of the tumor was not detected. No association was found between Gal3 and p53 expression levels and signs of aggressive tumor behavior. The data obtained in the study suggest that immunohistochemical markers reflect the processes characterizing the biological pathomorphism of the tumor and indicate a gradual loss of differentiation signs in more aggressive tumors. Conclusions: immunohistochemical markers changes reflect biological pathomorphism of the tumor, overexpression of ki67 and TTF1, as well as the loss of NIS, suggest a greater malignant tumor potential. The obtained data may help in individualized choice of surgical procedure

Immunohistochemical expression of podoplanin in patients with lichen planus: a cross sectional study

Event Abstract Back to Event Immunohistochemical expression of podoplanin in patients with lichen planus: a cross sectional study Ilaria Currò1*, Andrea Gabusi1, Dora Servidio1, Roberto Rossi1, Laura Felicetti1 and Davide Bartolomeo Gissi1 1 University of Bologna, Department of Biomedical and Neuromotor Sciences, Section of Oral Sciences, Italy Aim: The World Health Organization had included Lichen Planus (LP) among the risk conditions for malignant transformation, even if it is difficult to evaluate the real risk of malignant transformation in LP patients and it is difficult to identify a predictive marker of progression risk to Oral Squamous Cell Carcinoma (OSCC). Immunohistochemical analysis is a simple and reliable method which allows to evaluate the expression of a biomarker which may be correlated with an increased risk of malignant transformation in potentially malignant lesions of the oral cavity. Recently, few authors identified a relationship between dysplasia and podoplanin overexpression in patients with Oral Leukoplakia and proposed podoplanin as a predictive marker to identify Oral Leukoplakias likely to develop into OSCC. In the present cross-sectional study, we investigated a group of consecutive LP to evaluate a possible relationship between altered expression of podoplanin and the presence of dysplasia, and to compare the results with those obtained with other clinical and immunoistochemical variables. Materials and Methods. The population study consisted of 38 consecutive patients with a clinical and histological diagnosis of LP. The 38 patients were divided into 2 groups: 23 lichenoid lesions in which there was no dysplasia and 15 lichenoid lesions in which dysplasia was present with different degrees (11 LP with presence of mild dysplasia and 4 with presence of moderate dysplasia). Immunoistochemical expression of podoplanin, p53 and Ki67 was analyzed. Lesions with podoplanin expression in the suprabasal layer of the epithelium (≥ pattern 2 in Kawaguchi classification) were considered as positive, whereas the cut off for both p53 and Ki67 overexpression was set to 20% of positive cells. Statistical analysis: A multiple logistic regression model with stepwise selection was fitted to describe the relation between presence/absence of dysplasia (dependent variable) and the following independent variables: Ki67 (<20 vs >20), p53 (<20 vs > 20), podoplanin (<2 vs > 2), patient age (< 65 vs > 65), gender, smoking behavior, site, clinical appearance. A p value < .05 was considered statistically significant in all analyses. Results. The results of multiple logistic regression showed that podoplanin expression was the only variable significantly related to the presence of dysplasia (T=4.68; p < .01). Indeed, Podoplanin expression was observed in 5 of 23 cases of lichenoid lesions without dysplasia and in 12 of 15 cases of lichenoid lesions with dysplasia (Chi 12,465; p<.05). Statistical analysis didn’t find a significant relationship between the presence of dysplasia in LP and overexpression of ki67 (Chi 1,870; p=0,1715), overexpression of p53 (Chi 0,035; p=0,8510) and other clinical variables. Discussion. An altered expression of different biomarkers in LP patients may be uninformative about the risk of OSCC progression, because it might be influenced by tissue inflammation. The present study shows that podoplanin is a promising specific marker related to the presence of dysplasia in LP. If these preliminary results are confirmed in larger prospective cohort studies with an adequate follow up, immunohistochemical expression of podoplanin could be proposed in clinical practice as a marker to discriminate LPs at risk of developing cancer.

Ki-67 is an independent prognostic marker for the recurrence and relapse of oral squamous cell carcinoma.

As a nuclear and nucleolar protein, proliferation marker protein Ki-67 (Ki-67) serves a vital role in tumorigenesis due to its positive correlation with tumor proliferation. High expression of Ki-67 in the cell cycle from the G1 to M phase makes it a potential biomarker for certain tumors and useful for selecting medical treatment. However, the diagnostic value of Ki-67 in oral squamous cell carcinoma (OSCC) has not been fully evaluated. In the present study, the objective was the elucidation of the prognostic value of Ki-67 in a large number of OSCC patients. Ki-67 expression was detected by immunohistochemical staining methods in 298 OSCC specimens and 98 tumor-free oral mucosa specimens (62 dysplasia mucosa and 36 normal mucosa), acquired from Nanjing Stomatological Hospital, Medical School of Nanjing University (Nanjing, China). Expression of Ki-67 in normal tissues, dysplasia tissues and OSCC tissues was compared. Associations between Ki-67 expression and clinicopathological parameters were analyzed by χ2 test. Kaplan-Meier survival curves and Cox progression analysis were used to assess the diagnostic value of Ki-67 for OSCC. The results showed that Ki-67 expression was higher in OSCC tissues than in tumor-free tissues and that it increased with the progression of dysplasia in oral mucosa tissues. In addition, patients with high Ki-67 expression had a worse clinical outcome, including poor tumor differentiation (P=0.001), increased positive lymph node metastasis (P=0.006) and increased worst pattern of invasion type (P<0.0001). Kaplan-Meier survival analysis demonstrated that higher Ki-67 expression was associated with poorer overall survival (OS) (P=0.035), recurrence-free survival (RFS) (P=0.017), metastasis-free survival (MFS) (P=0.032) and disease-free survival (DFS) (P=0.018) times. Additional multivariate analysis demonstrated that Ki-67 expression was negatively associated with OS, DFS, RFS and MFS. In conclusion, Ki-67 overexpression is associated with the progression of OSCC and serves as an independent prognostic factor for OSCC patients.

Prognostic Value of Immunohistochemical Biomarkers in Patients with Astrocytic Brain Tumor

Objectives: Astrocytoma is a common primary malignant brain tumor and it is typically associated with poor outcome. In this study, we aimed to determine role of various immunohistochemical (IHC) biomarkers and their relationship with patient prognosis. Methods: Patients who underwent surgery for astrocytic brain tumor were selected. Tissue specimens were collected from surgically removed tumors and stained by various IHC stains. All-cause mortality was chosen for study endpoint. Results: A total of 133 patients with who underwent surgery for astrocytic brain tumor were included (mean age 38±19 and 49.6% male). During follow-up, 84 patients (63%) died and the median time of death was 8 months (IQR 4; 16) after hospital discharge. Patients who died had higher tumor grade (60.7% vs. 34.7%, p&lt;0.01). After adjustment of possible predictors, surgical type (HR=0.51, 95% CI 0.31-0.82, p&lt;0.01), expression level of Ki67 (HR=1.02, 95% CI 1.00-1.04, p&lt;0.05) and p53 (HR=1.01, 95% CI 1.00-1.02, p&lt;0.05) were independently associated with long term mortality. Kaplan-Meier estimation showed overexpression of WT1 (42% vs. 52%, p&lt;0.05) and Ki67 (27% vs. 58%, p&lt;0.001) are associated with poor survival. Conclusion: IHC biomarkers are independently associated with long term prognosis in patients with astrocytic brain tumor. Overexpression of WT1 and Ki67 marker are associated with poor survival.

Immunohistochemical Study of the Role of CK20, p53 and Ki-67 in Differentiation of Some Urothelial Lesions and Urothelial Carcinoma of the Urinary Bladder

AbstractBackground: Bladder cancer is the most common malig-nancy affecting the urinary tract. Distinguishing between urothelial dysplasia and carcinoma in situ based on histopatho-logical features alone is often difficult.Aim of Work: The aim of the current work is to distinguish between urothelial hyperplasia, urothelial dysplasia from urothelial carcinoma by using CK20, p53 and Ki-67 immu-nomarkers, determine the pattern and extent of their immuno-reactivity and correlate immuno-histochemical results with the clinicopathological parameters.Material and Methods: Fifty cases of urothelial carcinoma (38 cases) and some flat urothelial lesions (12 cases) were collected retrospectively. Tissue specimens were in the form of radical cystectomy (nine specimens) and transurethral resection of the tumor (TURT) (forty one specimens). They were stained by H&E, CK20, p53 and Ki-67 for immunohis-tochemical study. The relationship between their expression and the available clinicopathological features were evaluated.Results: CK20, p53 and Ki-67 expressions can signifi-cantly differentiate urothelial hyperplasia from urothelial dysplasia as the whole panel is negative in urothelial hyper-plasia and positive with scattered expression in urothelial dysplasia. Also pattern of expression of CK20, p53 and Ki-67 expression are suggesting for the diagnosis of either urothelial dysplasia or urothelial carcinoma in situ as their expressions show diffuse positivity throughout the urothelium in urothelial carcinoma in situ. These markers were statistically significant in grading of urothelial carcinoma as higher tumor grade associated with decreased CK20 expression and in-creased p53 and Ki-67 expression. CK20 expression was statistically significant in tumor stage as higher tumor stage was associated with decreased CK20 expression.Conclusions: Abnormal CK20 expression in urothelial cells plus overexpression of p53 and Ki-67 are indicators of dysplastic change in urothelial mucosa. A panel of CK20, p53 and Ki-67 can be a useful tool to confirm the diagnosis of CIS and can be helpful to distinguish it from dysplastic changes. Combined use of these markers may be helpful in assigning grade of urothelial carcinoma especially when histologic features are borderline.

Evaluation of Involvement of Axillary Lymph Nodes with Ki-67 Expression in Patients with Breast Cancer

Background: Breast cancer is the first leading cause of cancer-related deaths in women. Ki-67 is being used for evaluation of the prognosis of patients with breast cancer. Objectives: The aim of the current study was to explore the association of the involvement of axillary lymph nodes status with the expression of Ki-67 in patients with breast cancer. Methods: A total of 449 patients were enrolled followed by evaluation of the association of Ki67 levels with demographic, pathologic, and survival data of patients, using Chi-square, logistic regression models, student t test and Mann-Whitney. Results: We observed a significant relationship between the expression level of Ki-67 and stage of tumor (P = 0.012), positive progesterone receptor (P = 0.003), and subtype pathologic features (P < 0.05). Also, a significant difference was detected between Her2 and expression level of Ki-67 (P = 0.015). Survival analysis showed the association for Ki-67 (P = 0.02), age (P = 0.005), stage of tumor (P < 0.05), lymph node involvement (P = 0.001), and the Her2 (P = 0.024) with clinical outcome (e.g., overall survival or disease free survival) of patients with breast cancer. Conclusions: The results of this study demonstrated that the overexpression of Ki-67 was associated with large tumors, progesterone receptor expression, and stage of tumor, but it was not related with lymph node involvement.

Impact of cyclooxygenase-2 over-expression on the prognosis of colorectal cancer patients. An experience from Western Saudi Arabia.

Objectives:To evaluate cyclooxygenase-2 (COX-2) over-expression in colorectal cancer (CRC) and its role in carcinogenesis and prognosis.Methods:It was a retrospective study. Archival samples were obtained from Pathology Department at King Fahad Hospital, Madinah, Saudi Arabia, over 11 years’ period (January 2006 to December 2017). Samples were analyzed using immunohistochemistry for COX-2 and Ki67 over-expression in 324 CRC patients, 40 cases of colorectal adenomas and 20 cases of normal colonic mucosa.Results:Cyclooxygenase-2 over-expression was observed in 40% of normal colonic mucosa, 65% of colorectal adenoma and 84.6% of CRC cases. There were no significant correlations between COX-2 over-expression and age, gender, tumor site, or tumor size. However, COX-2 over-expression revealed highly significant correlations with tumor differentiation, lymph node metastasis, lympho-vascular invasion, distant metastasis, advanced stages, and high Ki67 expression. Univariate Kaplan-Meir survival analysis showed that patients with high COX-2 expression had significantly shorter periods of survival. Multivariate analysis by means of the COX-2 regression model revealed that high COX-2 over-expression, AJCC, and Ki67 expression were the only significant independent prognostic indicators.Conclusion:Cyclooxygenase-2 over-expression increases during normal-adenoma-carcinoma sequence, moreover COX-2 over-expression is associated with advanced tumor stage and Ki67 over-expression. These findings suggest a significant role of COX-2 in the carcinogenesis and prognosis of CRC in our study population.

Abstract B30: Bovine leukemia virus in breast tissue linked to increased cell proliferation and breast cancer risk

Abstract Purpose: To compare recent data sets on frequency of bovine leukemia virus (BLV) detection in breast tissue in different human populations, and association of BLV with a confirmed diagnosis of breast cancer and expression of common clinical biomarkers. Many risk factors are associated with breast cancer, but what causes initial molecular/cellular changes from normal to malignant is not well understood. Six types of human cancer are caused by viruses, and several viruses have been studied for a role in breast cancer. BLV is a common virus of US cattle (38% of beef herds, 89% of dairy herds, 90-100% of large dairy operations). BLV DNA and protein were previously identified in human tissues. Methods: Breast tissue specimens were archived formalin-fixed, paraffin-embedded tissue sections from sources mentioned below. In situ PCR (IS-PCR) was performed on intact deparaffinized sections on glass slides, using primers from the tax region (transforming gene), highly conserved and rarely deleted, as are most BLV genome regions as tumor progression occurs. BLAST sequence comparisons indicated primers had high homology only with BLV, and extremely low homology with human genomic sequences, including human endogenous retroviral sequences. Previous laboratory experiments confirmed this specificity and established appropriate controls for the assay. Sections were semiquantitatively scored for density of the digoxygenin-labeled IS-PCR product within mammary epithelial cells, upon microscopic examination by two independent examiners. Results: Previous data sets using samples from the Cooperative Human Tissue Network, USA (n=239) and New South Wales, Australia (n=96), showed BLV presence significantly more frequently in malignant tissue than in normal breast tissue from women with no breast cancer history. Odds ratios (OR) and confidence intervals (CI) were 3.07(1.66-5.69), p≤.001 and 4.72(1.71-13.05), p≤.003, respectively. New unpublished data indicate specimens from MD Anderson Cancer Center in Houston, TX (n=216) show an even higher OR (CI) of 5.59 (2.76-11.30), p≤.0001. Argentinian specimens showed lower frequency (22%) in malignant tissues than US (58%) and Australian specimens (80%). Cell proliferation markers, KI67 and HER2 overexpression were significantly associated with BLV presence in Argentinian malignant breast tissues. For 31 Australian subjects with breast cancer, archived normal breast tissues were available from surgery 3-10 years previous for an unrelated condition. For 23 (74%) of these, BLV was already present in normal tissue at least 3 years before cancer diagnosis, consistent with a causative temporal relationship between BLV presence and subsequent cancer development. Conclusions: New unpublished data indicate BLV in some Argentinian women, but the frequency in breast cancer tissue is lower than in US and Australian women. Tests for conventional prognosis/proliferation biomarkers (ER, PR, HER2, Ki67) in Argentinian specimens showed BLV presence significantly associated with moderate-high Ki67 level (p≤0.009) and HER2 overexpression (p≤0.0442), consistent with possible BLV role in enhanced cell proliferation. BLV’s mode of transformation is via the oncogenic protein (Tax), which inhibits host cell DNA repair via the base excision pathway. DNA damage observed in breast cancer cells, including driver mutations, could theoretically have been initiated due to DNA repair inhibition by BLV infection. Elucidating initiators for any cancer opens opportunities for primary and secondary prevention. For viruses, the reservoir (e.g., BLV-infected cattle) could be reduced, transmission to humans could be intercepted (e.g., education to avoid raw milk, raw beef appetizers), vaccines could be developed, and elimination of the virus might be achieved by developing BLV-targeting agents. Driver mutations already initiated by BLV might be targeted as part of personalized secondary prevention and/or therapy. Note: This abstract was not presented at the conference. Citation Format: Gertrude C. Buehring, HuaMIn Shen, Kimberly Baltzell, Jennette Sison, Savitri Krishnamurty, Pamela Lendez, Lucia Matinez-Cuesta, MariaVictoria Nieto-Farias, GuillerminaLaura Dolcini, MariaCarolina Ceriani. Bovine leukemia virus in breast tissue linked to increased cell proliferation and breast cancer risk [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B30.

Significance of calreticulin as a prognostic factor in endometrial cancer.

In patients with endometrial cancer, the expression and prognostic significance of calreticulin (CRT) remains to be fully elucidated. To investigate the role of CRT in endometrial cancer, the present study compared its expression status with clinicopathological characteristics and evaluated its prognostic significance. The expression of CRT, PKR-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), and Ki67 were assessed by immunohistochemistry and/or western blotting in endometrial cancer patients. The association of the expression of CRT, p-eIF2α and Ki67 with patient survival rate was assessed by Kaplan-Meier and Cox regression analyses. Low levels of CRT and an overexpression of Ki67 were significantly associated with the stage, histology, and differentiation of the primary surgery without doxorubicin (DOX) neoadjuvant chemotherapy (NAC) patient group and were significantly correlated with a short progression-free survival and the overall survival. A multivariate analysis revealed that CRT and Ki67 expression were independent prognostic indicators for endometrioid endometrial cancer. Low CRT expression and an overexpression of Ki67 were significantly associated with DOX-NAC and the histology (P<0.05) pre-NAC and post-NAC in the DOX-NAC patient group. Upon treatment of DOX-NAC, CRT, PERK and p-eIF2α protein content were overexpressed in DOX-sensitive endometrial cancer (P<0.05), whereas there was no significant difference in the DOX-resistant group. Low CRT expression in endometrial cancer is significantly associated with aggressive progression and poor prognosis. CRT may therefore serve as a molecular marker for predicting the progression and prognosis in DOX-resistant endometrial cancer patients.

Prognostic value of ki67 in BCG-treated non-muscle invasive bladder cancer: a meta-analysis and systematic review

ObjectivesThe aim of this study was to explore the prognostic value of ki67 as a marker in patients with non-muscle invasive bladder cancer (NMIBC) treated with BCG.MethodsStudies were systematically retrieved...

β-Catenin-driven adrenocortical carcinoma is characterized with immune exclusion.

AimAdrenocortical carcinoma (ACC) is characterized by overexpressed CTNNB1, which is reported to modulate immune exclusion. Cross talk between CTNNB1 and cancer immunity in ACC remains unclear.Materials and methodsIn silico reproduction of TCGA-ACC dataset (N = 92) and external validation using tissue samples were performed (N = 16). Expression data of CTNNB1, PD-1, and PD-L1 were extracted in silico and tumor-infiltrating lymphocytes (TILs) were profiled using code provided by Tumor IMmune Estimation Resource (TIMER). In-house formalin-fixed paraffin-embedded ACC samples were processed using immunohistochemical (IHC) staining for CTNNB1, CD45, PD-1, and PD-L1.ResultsIncreased CTNNB1 expression was significantly associated with worsened overall survival (OS) (P = 0.006). CD8+ cells were significantly associated with better OS (P = 0.02). Higher PD-L1 (P = 0.019), but not PD-1 expression (P = 0.325), was associated with better OS. CTNNB1 overexpression was significantly associated with increased tumor purity (r = 0.356, P = 0.002) and fewer TILs (r = −0.833, P = 0.029), decreased infiltrating CD8+ cells (P = 0.033), and increased infiltrating B cells (P = 0.026). CTNNB1 expression was negatively correlated with PD-L1 expression (r = −0.308, P = 0.006) but not with PD-1 expression (P = 0.067), which were externally validated (P = 0.032 for PD-L1 and P = 0.400 for PD-1). The Cox regression model encompassing gender, B cells, CD8+ cells, PD-L1, CTNNB1, and Ki-67 revealed that only Ki-67 overexpression remained significantly associated with OS (P < 0.001), while CTNNB1 showed marginal significance (P = 0.06). CTNNB1-overexpressed patients were more likely to have cortisol excess (P = 0.003).ConclusionACC with CTNNB1 overexpression is associated with poor prognosis and decreased immunity. Our findings suggest that CTNNB1-targeting therapy may overcome immune exclusion in ACC.

Ki-67 as a Prognostic Marker in Upper Urinary Tract Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

We systematically evaluated the prognostic significance of Ki-67 on survival outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). We searched the Embase, Scopus, and PubMed databases for all articles published up to February 2017 by following the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. The outcomes of interest included intravesical recurrence (IVR)-free survival, disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS). The associations between Ki-67 and the survival outcomes were expressed using a pooled hazard ratio (HR) and a 95% confidence interval (CI). A total of 12 articles, representing 1351 patients with a range from 37 to 475, met the eligibility criteria and were finally selected for this meta-analysis. The overexpression of Ki-67 was significantly associated with worse DFS (HR, 2.74; 95% CI, 1.58-4.74), CSS (HR, 2.26; 95% CI, 1.70-3.01), and OS (HR, 3.71; 95% CI, 1.78-7.75), but not IVR-free survival (HR, 0.77; 95% CI, 0.10-5.82). Interstudy heterogeneity was observed in the analysis of DFS (I2= 54%; P= .05) and IVR-free survival (I2= 81%; P= .005). The funnel plot test indicated no significant publication bias in the meta-analysis of survival outcomes. The results drawn in this meta-analysis suggest that the overexpression of Ki-67 might be a promising prognostic indicator predicting survival outcomes after RNU for UTUC. However, a large, well designed, prospective study is necessary to establish the prognostic value of Ki-67 in UTUC.

Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular profile in a population of West Algeria

Breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr virus (EBV) is a widely studied candidate virus. The objective of this study is to determine the association of EBV infection with infiltrating ductal carcinomas (IDC). This descriptive study was carried out in the laboratory of developmental biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the clinicopathological characteristics of the population. Of the 23 cases of IDC, we implemented the techniques Elisa, immunohistochemistry and in situ hybridization. To determine the serological profile, overexpression of onco-proteins EBNA-1, HER2, the mitotic index Ki67 and detection of the presence of the viral genome. The mean age is 57.40±4, SBR II predominates with 70%, pN+ (27%), RE+ (58%), RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1 P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79 serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile (p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in the tumors 43% representing an inverse relationship with the overexpression of Ki67 and a positive relationship with the overexpression of HER2. In our study we found an association with the presence of the EBV virus and the IDC studied.

Immunolocalization of CD163+ Tumor-Associated Macrophages and Symmetric Proliferation of Ki-67 as Biomarkers to Differentiate New Different Grades of Laryngeal Dysplasia.

To evaluate CD163+ tumor-associated macrophages (TAMs), Ki-67, and cyclin D1 to differentiate laryngeal dysplasia in the 2017 World Health Organization classification. Immunohistochemistry for CD163, Ki-67, and cyclin D1 was performed using paraffin-embedded specimens. CD163+ TAMs infiltrating the epithelium were estimated. Ki-67 and cyclin D1 were evaluated in four parts of the epithelium-basal, parabasal, middle third, and upper third layers. In total, 133 specimens were analyzed, including low-grade dysplasia (n = 31), high-grade dysplasia (n = 49), carcinoma in situ (n = 23), and normal mucosa (n = 30). CD163+ TAMs infiltrating the epithelium were significantly higher in high-grade dysplasia than in low-grade dysplasia. In the basal layer, Ki-67+ and cyclin D1+ cells were overexpressed in high-grade dysplasia (P < .0001). The area under the curve was 0.958 for Ki-67 and 0.909 for CD163+ TAMs (P < .0001). CD163+ TAMs infiltrating the epithelium and Ki-67 overexpression in the basal layer may serve as biomarkers to differentiate low-grade dysplasia from high-grade dysplasia of the larynx. A symmetric proliferative pattern was observed during laryngeal carcinogenesis following Ki-67 overexpression.

Correlation between the clinicopathological features and prognosis in patients with extranodal natural killer/T cell lymphoma

ObjectiveTo investigate the correlation between the clinicopathological features and prognosis in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). MethodsOne hundred and four patients diagnosed with ENKTCL at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China from November 1991 to September 2011 were included in the study. The clinicopathological features and their correlations with disease prognosis were evaluated in these patients. ResultsThe number of effective follow-up cases was 56 (53.8%) by the end of last follow-up in October 2015. Univariate survival analysis showed that granzyme B, perforin, and Bcl-2 expression was significantly associated with a poor prognosis in ENKTCL (P = 0.033, 0.004, and 0.034, respectively), whereas platelet-derived growth factor receptor-alpha (PDGFRA) expression was significantly associated with a better prognosis (P = 0.034). Ki-67 overexpression (≥50%) was significantly associated with a poor prognosis (P = 0.017). Different treatment approaches were also associated with prognosis (P = 0.014); specifically, the efficacies of combination treatments including chemotherapy and radiotherapy, and autologous hematopoietic stem cell transplantation were significantly better than those involving radiotherapy and chemotherapy alone. Patient gender, age, tumor location, staging, the presence of B symptoms, pretreatment lactate dehydrogenase levels, and β2-microglobulin levels were not associated with the prognosis of ENKTCL (P > 0.05). However, multivariate analyses showed that the treatment approach and all the immune markers were not independent prognostic factors for ENKTCL. ConclusionGranzyme B, perforin, and Bcl-2 expression and Ki-67 overexpression (≥50%) might be adverse prognostic factors for ENKTCL, whereas PDGFRA-positivity suggested a better disease prognosis. In addition, different treatment approaches might be closely related to patient prognosis.

Immunohistochemical Expression of Ki67 and HER2 in Colorectal Cancer Compared to Adenomatous and Normal Samples

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. Due to the high rate of mortality in advanced metastatic stages, finding new detecting techniques seems to be necessary. Objectives: This study aimed to investigate the immunohistochemical expression of Ki67 and human epidermal growth factor receptor 2 (HER2) in colorectal cancer compared to adenomatous and normal samples. Methods: This case-control study was conducted to evaluate Ki67 and HER2 protein immunohistochemical (IHC) expressions in 137 colorectal formalin fixed paraffin-embedded tissue blocks. The blocks were classified into 3 groups; normal (n = 36), adenomatous (n = 38), and adenocarcinoma (n = 63). All tissue blocks were selected through convenience sampling method from the archive of pathology in Ali-Ebne-Abitaleb Hospital, Zahedan, Iran from 2010 to 2015. The sections were evaluated, using semi-quantitative scoring. Ki67 and HER2 expressions were reported as negative and positive. Clinicopathological characteristics were also assessed. The data was analyzed by Kruskal-Wallis and Chi-square or Fisher tests. The significance level set as P < 0.05. Results: The expression of Ki67 in CRC, adenomatous, and normal colorectal tissues were 79.30%, 44.80%, 25.00%, and in HER2 were 54.00%, 36.80%, and 19.40%, respectively. Ki67 and HER2 overexpressions were significantly higher in CRC than the adenomatous and normal tissues (P < 0.05). Ki67 overexpression was significantly correlated with differentiation grade of tumor (P = 0.0002) and also HER2 expression was significantly associated with tumor type (P = 0.003). Conclusions: Considering the significant overexpression of Ki67 and HER2 in CRC, it seems that these biomarkers can be used as useful predictors in primary screening and identifying of CRCs. Further research should be conducted on this matter.

Is Ki-67, keratin 16, involucrin, and filaggrin immunostaining sufficient to diagnose inflammatory linear verrucous epidermal nevus? A report of eight cases and a comparison with psoriasis vulgaris.

Inflammatory linear verrucous epidermal nevus and linear psoriasis are sometimes hard to differentiate clinically and pathologically. Although immunohistochemical expression of keratin 10 (K10), K16, Ki-67, and involucrin may be useful for differentiating both entities, these results have been reported in only a few cases. We collected data from 8 patients with inflammatory linear verrucous epidermal nevus, 11 with psoriasis vulgaris, and 8 healthy controls and evaluated immunohistochemical expression of Ki-67, K16, involucrin, and filaggrin among them. Ki-67 and K16 overexpression was similar in inflammatory linear verrucous epidermal nevus and psoriasis vulgaris compared with normal skin. Although staining for involucrin showed discontinuous expression in parakeratotic regions in 4 inflammatory linear verrucous epidermal nevus cases, it was continuous in the other 4 cases and in all psoriasis vulgaris cases. Filaggrin expression was present in hyperkeratotic regions but scarce in parakeratotic areas in both inflammatory linear verrucous epidermal nevus and psoriasis vulgaris. The immunostaining pattern of Ki-67, K16, involucrin, and filaggrin may be insufficient to discriminate inflammatory linear verrucous epidermal nevus from psoriasis vulgaris.

Clinicopathological and prognostic significance of Ki-67 immunohistochemical expression in gastric cancer: a systematic review and meta-analysis

The prognostic significance of Ki-67 in patients with gastric cancer (GC) remains controversial. The aim of our meta-analysis is to evaluate its association with clinicopathological characteristics and prognostic value in patients with GC. PubMed, EMBASE, and Web of Science were systematically searched up to May 2017. Twenty-two studies including 3,825 patients with GC were analyzed. The meta-analysis indicated that the incidence difference of Ki-67 expression in GC patients was significant when comparing the older group to younger group (odds ratio [OR] =1.44, 95% confidence interval [CI] 1.19, 1.75), lymph node positive group to negative group (OR =1.49, 95% CI 1.20, 1.84), the large size tumor group to the small size tumor group (OR =1.27, 95% CI 1.24, 1.68) and the TNM stage III+IV group to TNM stage I+II group (OR =2.28, 95% CI 1.66, 3.12). However, no statistical differences existed in gender. The detection of Ki-67 significantly correlated with the overall survival of patients (hazard ratio =1.51, 95% CI 1.31, 1.72). Our study suggested that Ki-67 overexpression was associated with poor prognosis in GC patients. Ki-67 positive rates may be associated with age, lymph node metastasis, tumor size, and TNM staging system in GC patients.

Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors: A systematic review and meta-analysis.

Background:Ki67 is a good marker of cell proliferation in a variety of tumors. High ki67 levels are usually associated with poor prognosis. However, the relationship between Ki67 expression and the risk of malignancy of gastrointestinal stromal tumors (GISTs) is still poorly defined. The current meta-analysis was initiated to address this issue.Methods:Studies reporting Ki67 expression and the risk of malignancy in GIST were found by searching Cochrane Library, PubMed, Medline, and Embase until October 31, 2016. A total of 9 studies involving 982 patients were included. Pooled odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated using a fixed-effect model.Results:Meta-analysis showed no significant difference in the incidence of Ki67 overexpression between the very low NIH group and the low NIH group (OR: 0.66, 95% CI: 0.25–1.76; P = .41, Pheterogeneity = .25). However, the incidence of Ki67 overexpression gradually increased from the low NIH group to the high NIH group (OR: 0.46, 95% CI: 0.27–0.80; P = .005, Pheterogeneity = .13) and (OR: 0.22, 95% CI: 0.15–0.34; P < .00001, Pheterogeneity = .33).Conclusions:There were more GIST patients with Ki67 overexpression in the intermediate and high NIH groups than in the low NIH group. Ki67 overexpression may be a useful marker of the risk of malignant GIST transformation.