Ki-67 Immunoexpression Research Articles

The Correlation of Nottingham Prognostic Index with Immunoexpression of ER, PR, HER2, and Ki67 in Breast Cancer Tissue

Abstract Background In the underdeveloped and developing countries, the application of immunohistochemistry (IHC) to assess the status of oestrogen receptor (ER), progesterone receptor (PR), HER2 receptor, and Ki67 proteins in formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma is utterly hindered by high cost, long procedure, and need for both skilled operator and pathologist. The objective of this study was to evaluate the correlation of Nottingham prognostic index (NPI) with immunoexpression of ER, PR, HER2, and Ki67 proteins in the formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma. The ethical approval reference number is IRBRTA 306/2560. Methods Two hundred and forty primary invasive breast carcinoma cases were determined their NPI which was calculated as [0.2 × maximum tumour diameter in cm] + tumour grade + axillary lymph node score. Tumour grade was given a score 1 to 3 based on the Nottingham Combined Histologic Grade system (Elston-Ellis modification of Scarff-Bloom-Richardson grading system) of primary invasive breast carcinoma. Axillary lymph node metastasis (ALNM) was given a score 1 if no ALNM, a score 2 if 1 to 3 metastatic nodes, and a score 3 if at least 4 nodal involvement. The correlation between NPI and the IHC status of ER, PR, HER2, and Ki67 was analysed at the 95% confidence interval. Results The NPI had a significant association with the immunoexpression of ER, PR, and Ki67 proteins. There was no correlation with HER2 immunohistochemical reactivity. The proposed NPI score less than 4.5 will significantly correlate with positive immunoexpression of ER and PR. The NPI score greater than or equal to 4.5 will correlate with high Ki67. Conclusion The NPI might have a role in predicting the results of ER, PR and Ki67 expression in the formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma, if immunohistochemical method is unavailable.

Computerized Evaluation of the Immunoexpression of Ki-67 Protein in Odontogenic Keratocyst and Dentigerous Cyst.

Evaluation and comparison of odontogenic keratocysts and detigerous cysts immunoexpression and immunostaining intensities of Ki-67 antigen by assessing the whole extent of the epithelium (all epithelium layers in combination) and each layer individually. Ki-67 immunoexpression was evaluated in 15 odontogenic keratocysts and 6 dentigerous cysts using automated methods and the Aperio Technologies Inc. computer system. No statistically significant differences were observed in immunoexpression nor in immunostaining intensities between both lesions. Also, no statistically significant differences were found between odontogenic keratocysts from maxilla versus mandible nor primary versus recurrent. However, odontogenic keratocyst showed a significantly higher cellular proliferation index in the suprabasal layers compared to the basal layer. Assessment of the cellular proliferation index through a computerized system enabled the evaluation of all epithelial tissue without field selection. The increased Ki-67 immunoexpression in suprabasal layers of odontogenic keratocyst suggests a different biological behavior and more aggressive proliferation potential when compared to dentigerous cyst. The same result was found in recurrent odontogenic keratocysts when compared with primary ones. The odontogenic keratocysts of the maxilla and mandible have similar Ki-67 immunoexpression. The evaluation of cellular proliferation only by immunohistochemical analysis with Ki-67 antigen does not provide enough data to elucidate the biological behavior of odontogenic keratocyst.

Polyphenol rich fruit attenuates genomic instability, modulates inflammation and cell cycle progression of offspring from fatty acid intake maternal

The aim of this study was to investigate the effect of juçara (Euterpe edulis Mart.) supplementation on the maternal trans fatty acids intake in the livers of 21-day-old offspring. In order for this to happen, histopathological analysis, cytogenetic status, inflammation (COX-2 and TNF-alpha) and cell cycle progression were investigated in this setting. On the first day of pregnancy, female rats were distributed into four groups, as follows: control diet (C), control diet with 0.5 % juçara supplementation (CJ), diet enriched with hydrogenated vegetable fat, rich in TFAs (T), or T diet supplemented with 0.5 % juçara (TJ) during pregnancy and lactation. Juçara pulp induced liver regeneration in newborns exposed to maternal trans fatty acids. A significant decrease in the number of micronucleated hepatocytes was observed in animals exposed to trans fatty acids and treated with juçara. COX-2 and TNF immunoexpression was reduced in animals treated with juçara pulp. Furthermore, a decrease of Ki-67 immunoexpression was detected after treating trans fatty acids intake with juçara. Taken together, our results demonstrate that juçara pulp is able to prevent tissue degeneration and mutagenicity because it decreases inflammation and cell cycle control induced by maternal trans fatty acids in liver cells of rat offspring.

Morphological development of the human cochlear nucleus

Morphological studies in developing brain determine critical periods of proliferation, neurogenesis, gliogenesis, and apoptosis. During these periods both intrinsic and extrinsic pathological factors can hamper development. These time points are not available for the human cochlear nucleus (CN). We have used design-based stereology and determined that 18–22 weeks of gestation (WG) are critical in the development of the human CN. Twenty-three fetuses and seven postnatal brainstems were processed for cresyl violet (CV) staining and immunoexpression of NeuN (neurons), GFAP (astrocytes), Ki-67 (proliferation) and TUNEL (apoptosis) and 3-D reconstruction. The volume of CN, total number of neurons selected profiles and the volume of neurons and their nuclei were estimated. Data were grouped (G) into: G1:18-20 WG, G2: 21–24 WG, G3: 25–28 WG and G4 >29 WG. The dimensions of morphologically identified neurons were also measured. The CN primordium was first identifiable at 10WG. Definitive DCN (Dorsal cochlear nucleus) and VCN (ventral cochlear nucleus) were identifiable at 16 WG. There was a sudden growth spurt in total volume of CN, number of neurons and astrocytes from 18 WG. We also observed an increase in proliferation and apoptosis after 22 WG. The number of neurons identifiable by CV was significantly lower than that by NeuN-immunostaining till 25 WG (p = 0.020), after which, both methods were equivalent. Eight morphological types of neurons were identifiable by 26 WG and could be resolved into four clusters by volume and diameter. The CN changed orientation from small, flat and horizontal at 10–16 WG to larger and oblique from 18WG onwards. Prevention of exposure to noxious factors at 18–22 WG may be important in preventing congenital deafness.

The Expression Analysis of Intestinal Cancer Stem Cell Marker Lgr5 in Colorectal Cancer Patients and the Correlation with Histopathological Markers.

Cancer stem cells (CSCs) have frequently been utilized in the cell characterization and identified responsible for tumor development, metastasis, recurrence, and chemoresistance. CSC surface markers function in cancer cell signaling and are indicated as potential biomarkers for cancer diagnosis and prognosis. As well, dysregulation of cancer-related signaling pathways could promote CSC development and progression. Our aim was to evaluate the expression of colorectal CSC markers and their correlation with cancer proliferation and angiogenesis. In this case-control study, total RNA was extracted from a total of 74 colorectal tumors and 74 adjacent normal tissue biopsies. Then, using a quantitative real-time PCR, the relative expression levels of Lgr5 and Lrig1 were measured in all malignant and healthy samples. Also, immunohistochemical (IHC) staining of tumor tissues was performed for Ki-67 (proliferation) and CD34 (angiogenesis) markers, and the immunoexpression staining scores were obtained. The diagnostic value of the genes was evaluated using receiver operating characteristic (ROC) curve. Possible correlation between CSC markers and immunohistochemical markers in CRC was analyzed by Pearson's correlation test and linear regression. The expression level of Lgr5 in tumor samples showed a significant increase compared with normal samples (p < 0.001) with a fold change of 2.54 (± 0.182). However, there was no significant difference in the relative expression of Lrig1 gene in tissue samples of healthy subjects and patients. The analysis of the ROC showed an AUC of 0.92 for Lgr5 and sensitivity 80% and specificity 96%. Further analysis revealed a significant correlation between mRNA levels of Lgr5 and immunoexpression of Ki-67 (r2 = 0.680, p < 0.001). The high expression levels of Lgr5 found in tumor tissues were correlated with histological parameters, indicating a significant role in CRC development and diagnosis.

Immunoexpression of Ki-67 in determining prognosis of oral cavity squamous cell carcinoma

Introduction: Several researchers have been stated that the right prognosis of oral squamous cell carcinoma (OSCC) can be achieved through assessment of tumor clinical staging and tumor histopathological grading as well. The use of biomarker in histopathological grading is obviously helpful to ensure the prognosis. Objective of this study was to determine the correlation between expression of Ki-67 and histopathological grading of OSCC. Methods: A retrospective study was conducted by assessing 20 cases of paraffin-embedded OSCC derived from the Department of Pathology Anatomy of Hasan Sadikin Hospital Bandung in 2013. The OSCC performing was stained by hematoxylin-eosin. While, antibodies Ki-67 was used in immunohistochemistry reaction to determine the relation of expression of Ki-67 with histopathologic grade of OSCC for predicting a prognosis. Results: The result show that distribution of Ki-67 expression were vary from 20% to 80% in each case. Ki-67 intensity was also distributed from weak, moderate and strong. Conclusion: There is a significant correlation between Ki-67 immunoexpression and the histopathological grading of squamous cell carcinoma (p &lt; 0.01), thus, Ki-67 can be used to predict a prognosis.Keywords: Immunoexpression, Ki-67, prognosis, oral cavity squamous cell carcinoma

Immunoexpression of Ki-67 and Cyclooxygenase-2 in Odontogenic Keratocyst and Dentigerous Cyst: A Comparative Study

Aims: To evaluate the expression of Cyclooxygenase-2 (COX-2) in odontogenic keratocyst (OKC) and dentigerous cyst and correlate it with Ki-67 expression in these lesions.Material and Methods: This study was carried out on 32 paraffin embedded specimens of dentigerous cyst and OKC. 16 samples obtained from healthy mucosa served as controls. Slides prepared from paraffin-embedded sections were immunohistochemically stained for Ki-67 and COX-2 and immunoreactivity of the two markers was evaluated using index of positivity and staining intensity. Statistical analysis was performed using Mann-Whitney and Spearman’s correlation tests.Results: Ki-67 and COX-2 expression in OKC and dentigerous cyst was found to be significantly higher than those observed in healthy mucosa groups (p < 0.05). The expression of the two markers was significantly higher in OKC than in dentigerous cyst. A positive correlation was found between the two markers in both lesions.Conclusions: Increased expression of Ki-67 and COX- 2 in OKC is an indicator of the high mitotic activity of these lesions compared with dentigerous cyst. COX-2 is implicated in odontogenic epithelial proliferation in OKC and dentigerous cyst.

Expression of p-16, Ki-67 and p-53 markers in dysplastic and malignant lesions of the oral cavity and oropharynx.

Background:Understanding the markers for predicting degree of dysplasia and progression to malignancy can help early identification and prompt treatment of patients with oral cancers. In this study, we aim to identify and characterize different tumor suppressor genes such as p-53 and p-16 and proliferation marker Ki-67 in defining stages of dysplasia of oral mucosa and grading of tumor.Settings and Design:Oral biopsy tissues (for neoplastic lesions) received for histopathological evaluation were included in the study. The sections were processed for H&E staining, and 112 cases were chosen for immunohistochemical study. The data were analyzed by Chi-square and z-tests using software SPSS.Results:We found significant correlation between degree of dysplasia and p-16 immunoexpression with 16.7% of cases showing positivity in oral intraepithelial neoplasia (OIN) I cases as compared to 25% in OIN II and 77.8% in OIN III. Ki-67 immunoexpression correlated significantly with both histological type and grade of tumor with increased expression and intensity seen in malignant cases (66.3%) as compared to benign (10%) and premalignant cases (37%) and higher Ki-67 immunoexpression in poorly differentiated tumors (75%) than well-differentiated tumors (12.2%). Regarding p-53 immunoexpression, positive staining was seen in only malignant cases and premalignant cases.Conclusions:Ki-67 and p-16 can be useful as a marker of degree of dysplasia and transformation to malignancy. Ki-67 can also serve as a marker of degree of differentiation of tumors. Hence, they can serve as important ancillary markers to analyze the transition to carcinoma, dysplasia and progression of tumor.

Evaluation of the Chemopreventive Activity of Grape Skin Extract Using Medium-term Oral Carcinogenesis Assay Induced by 4-Nitroquinoline 1-Oxide.

The aim of this study was to evaluate the chemoprotective potential of grape skin extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). Male Wistar rats were distributed into four groups (n=5, per group): Control Group: free access to commercial diet and drinking water for 12 weeks; 4NQO Group: received 4NQO diluted in drinking water daily, for 12 weeks; Grape Skin Extract Group: free access to water and received grape skin extract incorporated with diet for 12 weeks; 4NQO + Grape Skin Extract Group: received 4NQO in drinking water daily and grape extract incorporated with diet for 12 weeks. Animals treated with grape skin extract revealed a significant reduction in epithelial dysplasia. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and ki-67 immunoexpression was reduced in animals treated with grape skin extract. Western blot analysis showed a significant decrease of p-NFκB p50 and MyD88 protein expression in the groups treated with grape skin extract. Copper-zinc superoxide dismutase, manganese superoxide dismutase, and catalase gene expression did not present any statistically significant differences (p>0.05). Grape skin extract displayed chemopreventive activity in oral carcinogenesis assays as depicted by its antioxidant, anti-proliferative and anti-inflammatory properties.

Histological Evaluation of the Emerging Role of Adipose Stem Cells-Derived Exosomes in Cutaneous Wound Healing in Albino Rats

Prolonged healing and scar formation are two major challenges in treating wounds, resulting in physical, mental and socioeconomic burden to the affected subjects. Exosomes (Exos) are naturally secreted vesicles playing a vital role in the transfer of RNA to neighboring or distant recipient cells and there are numerous on-going studies on their role of in tissue regeneration and wound healing.Aim of the work: Evaluation of the efficiency of Exos derived from adipose stem cells on cutaneous wound healing in adult male albino rats.Materials and Methods: Thirty-four rats were divided into three groups; Group I: control. Group II: a dorsal cut wound (1.5 × 1.5 cm) was done to each rat. Group III: the same wound was done and rats were injected with 200μ PKH26-labeled Exos intravenously. Rats were sacrificed after 21 days. Skin sections were subjected to hematoxylin and eosin (HandE), Mallory's trichrome and orcein stains, alpha smooth muscle actin (α-SMA) and Ki67 immunohistochemical stains.Results: Skin sections from group II showed scar formation, lost epidermal layers and hair follicles. There was significant increase in collagen fibers and α-SMA immunoreaction, with significant decrease in elastic fibers and Ki67 immunoexpression compared to the control. In group III, the skin revealed almost normal histology, significant decrease in collagen fibers and α-SMA, with significant increase in elastic fibers and Ki67 immunoreaction compared to group II.Conclusion: Exos injection has demonstrated a beneficial effect on cutaneous wound healing and could prevent scar formation in adult male albino rats.

The Role of Ki-67 Immunoexpression in Predicting the Biological Behavior of Retinoblastoma Tumor in Tanzania

The Role of Ki-67 Immunoexpression in Predicting the Biological Behavior of Retinoblastoma Tumor in Tanzania

Histopathological Study of Prostatic Carcinoma in Relation to Gleason Grade, Serum PSA and Ki67 Immunomarker

Introduction- Carcinoma of prostate (CaP) is the second most common cancer in men.Gleason’s score (GS) and pretreatment serum prostate specific antigen (sPSA) levels are important parameters in diagnosis and therapeutic decision making. Recent studies have found that GS tends to undergrade tumors and sPSA levels are not cancer specific. The present study highlights correlation between immunomarker Ki67, GS and sPSA which provides a objective method of grading tumors and helps in better prognostication of patients. Objectives- 1. To study histopathology of prostate carcinoma and its variants and assign them Gleason score as per the Gleason grading system. 2. To study Ki-67 immunoexpression in prostate carcinoma. 3. To correlate Ki-67 expression, Gleason scoring and serum prostate specific antigen levels in prostate carcinoma Methods -A retro-prospective study was done on 100 specimens of prostate carcinoma from the year 2010-2015 in Department of Pathology of ESIC Medical College and PGIMSR, Rajajinagar, Bangalore for a period of 18 months(November2013-April2015).Each case was assigned Gleason score and subjected to immunohistochemistry for Ki67 expression. Results of Ki67 expression was correlated with Gleason score and PSA levels. Results-Out of the 100 cases studied, all case were of acinar/usual adenocarcinoma-WHO type. 40 cases were moderately differentiated, 39 cases were high grade tumors and 21 cases were intermediate grade tumors. Serum PSA levels increased with increase in GS. Ki67 labelling index showed a proportionate increase with increase in GS and serum PSA which was statistically significant. Conclusion- Ki67 is a new emerging biomarker which is significantly associated with tumor grade and pretreatment PSA levels and can be used as an additive parameter or a substitution to known prognostic variables to aid in therapeutic interventions.

Mast cells and immunoexpression of FGF-1 and Ki-67 in rat subcutaneous tissue following the implantation of Biodentine and MTA Angelus.

To compare the formation of fibrous capsules around Biodentine and MTA Angelus implants as well as the participation of fibroblast growth factor-1 (FGF-1) and mast cells in the tissue response to these endodontic materials. Sixty polyethylene tubes filled with Biodentine or MTA, and empty tubes (control group) were implanted into the dorsal subcutaneous tissues of male rats. After 7, 15, 30 and 60days, the specimens were embedded in paraffin and the number of fibroblasts and mast cells was quantified in the sections stained with Masson's trichrome or Alcian Blue, respectively. FGF-1 and Ki-67 were detected by immunohistochemistry, and the number of immunolabelled cells was computed. The collagen content was estimated in the picrosirius red-stained sections. The data were subjected to two-way ANOVA followed by Tukey's test (P≤0.05). The capsules were associated with a significant increase (P<0.0001) in the number of fibroblasts and mast cells, and in the collagen content over time. A significant decrease (P<0.0001) in the immunoexpression of FGF-1 and Ki-67 was observed in all groups from the 7th-60th day. At 60days, the number of fibroblasts (P=0.0226) and the collagen content (P<0.0001) were significantly greater in MTA than Biodentine specimens, while the greatest number of mast cells and FGF-1-immunolabelled cells was observed in Biodentine specimens (P<0.0001). A significant difference in Ki-67 immunoexpression was not detected between specimens of Biodentine and MTA. The collagen-rich capsule formed slowly around Biodentine in comparison with MTA. FGF-1 and mast cells participated in capsule remodelling, stimulating fibroblast proliferation and subsequent collagen production, in response to subcutaneous implants.

Treponema denticola chymotrypsin-like proteinase is present in early-stage mobile tongue squamous cell carcinoma and related to the clinicopathological features.

Certain periodontopathogenic bacteria have been linked to cancers. Treponema denticola (Td) is associated with severe periodontitis. Chymotrypsin-like proteinase (CTLP), a major virulence factor of Td, can degrade various host proteins and peptides, and modulate inflammatory responses. However, the role of Td in the tongue carcinogenesis remains unknown. This study aimed to investigate the presence of Td-CTLP in early-stage mobile tongue squamous cell carcinoma (MTSCC) and its relation to clinical and pathological characteristics. The immunopositivity of Td-CTLP was assessed in samples obtained from 60 patients with MTSCC and associated with their clinicopathological data. Additionally, Td-CTLP expression was compared with immunoexpression of matrix metalloproteinases (MMP-8 and MMP-9), toll-like receptors (TLR-2, TLR-4, TLR-7 and TLR-9), c-Myc, Ki-67, Bmi-1 and Snail. Treponema denticola-chymotrypsin-like proteinase was present in 95% of MTSCC tumours of which many (40.4%) showed high immunopositivity. Td-CTLP positivity was significantly associated with invasion depth, tumour diameter and the expression of TLR-7, TLR-9 and c-Myc. High Td-CTLP immunopositivity in younger patients (≤ 60 years old) predicted early relapse. Our data indicate that Td and its CTLP are present in early-stage MTSCC carcinoma and may contribute to carcinogenesis, and therefore provide novel perspectives into intervention and therapeutic measures of MTSCC.

Protective effects of purple carrot extract (Daucus carota) against rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

The aim of this study was to evaluate the chemopreventive potential of purple carrot extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). For this purpose, histopathological analysis, proliferative status, antioxidant activity and inflammatory status were investigated in this setting. A total of 20 male rats were distributed into four groups as follows (n = 5 per group): Group 1-free access to water and commercial diet for 12weeks; Group 2-received 4NQO at 50ppm dose in drinking water daily and commercial diet for 12weeks; Group 3-free access to water and received diet supplemented with purple carrot extract (0.1g/kg) for 12weeks; and Group 4-received 4NQO at 50ppm dose in drinking water daily and diet supplemented with purple carrot extract (0.1g/kg) for 12weeks. Histopathological analysis revealed that animals treated with purple carrot extract reduced the oral lesions such as dysplasia and squamous cell carcinoma. Animals with oral pre-neoplastic lesions and treated with purple carrot extract decreased ki-67 and 8-OHdG immunoexpression. Moreover, pNFκBp50 and MyD88 protein expressions were decreased after purple carrot treatment associated or not with 4NQO exposure. SOD-Mn mRNA levels increased with treatment with purple carrot extract as well. In conclusion, our results demonstrated that purple carrot extract was able to protect oral lesions induced by 4NQO in Wistar rats as a result of antioxidant activity, anti-inflammatory potential and antiproliferative and antimutagenic actions.

BRCA1, Ki67, and β-Catenin Immunoexpression Is Not Related to Differentiation, Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian Carcinoma.

The purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and β-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival. For this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included. BRCA1, Ki67, and β-catenin expression was assessed using tissue microarray-based immunohistochemistry. Women with HGSOC were significantly more likely to have advanced-stage disease (P < 0.001), higher CA125 levels (P < 0.001), postsurgery residual disease (P < 0.01), and higher rates of disease progression and recurrence (P = 0.001). The percentage of women with HGSOC whose tumors expressed Ki67 was significantly higher compared with women with LGSOC (P < 0.001). The expression of BRCA1 and β-catenin did not differ between LGSOC and HGSOC (P = 0.12 and P = 1.00, respectively). The clinicopathological features and the response to platinum-based chemotherapy did not differ according to the BRCA1, Ki67, and β-catenin expression in either group. In HGSOC, only International Federation of Gynecology and Obstetrics stage was independently associated with poor survival (PFS and OS). Ki67 expression was significantly higher in HGSOC. BRCA1 and β-catenin expression did not differ between LGSOC and HGSOC samples. BRCA1, Ki67, and β-catenin expression was neither related to clinicopathological features, response to platinum-based chemotherapy, nor survival. Only International Federation of Gynecology and Obstetrics stage remained associated with poor survival in women with HGSOC.

MCM3: A Novel Proliferation Marker in Oral Squamous Cell Carcinoma.

The present study sought to evaluate and compare the immunoexpression of proteins minichromosome maintenance (MCM) 3 and Ki-67 in oral squamous cell carcinoma (OSCC) to assess the potential of these proteins as markers of cellular proliferation. Twenty-eight cases of OSCC, 9 of tumor-free resection margins (TM), and 4 of non-neoplastic oral mucosa (NNM) were subjected to immunohistochemistry to detect the expression of proteins MCM3 and Ki-67. All OSCCs demonstrated positivity for both proteins. In these tumors, greater MCM3 immunoreactivity was observed in comparison with Ki-67, whereas TMs and NNMs exhibited greater Ki-67 expression compared with MCM3. The immunoexpression of Ki-67 seemed to be influenced by the inflammatory process, particularly in TM and NNM. Our findings indicate that although both MCM3 and Ki-67 represent reliable markers of cellular proliferation in OSCC, as MCM3 expression does not appear to be influenced by external factors, this protein may emerge as a novel marker of cellular proliferation in these types of tumors.

Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs.

BackgroundMismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the development of this odontogenic neoplasm.Material and MethodsImmunohistochemical assays to determine the presence of proteins hMSH2, hMLH1 and Ki-67 were performed in 80 ameloblastomas (40 solid and 40 unicystic) and five tooth germs.ResultsUnicystic ameloblastomas showed higher MMRP expression (hMLH1: 62.5 ± 43.4; hMSH2: 83.3 ± 47.8) than did solid ameloblastomas (hMLH1: 59.4 ± 13.5; hMSH2: 75.8 ± 40.2). Additionally, the cell proliferation index assessed by Ki-67 was inversely proportional to the expression of MMRP. Comparison between tooth germs and ameloblastoma revealed significantly higher expression of hMLH1, hMSH2 and Ki-67 in tooth germs (p=0.02).ConclusionsThe differences of MMRP and Ki-67 immunoexpression between ameloblastomas and tooth germ suggest that alterations in the MMRP mechanisms could participate in the biological behavior of ameloblastomas. Key words:hMLH1, hMSH2, Ki-67, Ameloblastomas, Tooth germs.

Proliferative Index (Ki67) for Prediction in Breast Duct Carcinomas

Background and objectives: To date, many tumor markers have been used to predict prognosis and therapeutic response in patients with breast cancer. The well established and routinely applied tumor markers are the estrogen-receptor, progesterone-receptor and Her2/neu-receptor. In the current study, we aimed to highlight any association of the proliferation index (Ki67) in breast infiltrative duct carcinoma with the tumor grade, tumor size and nodal status in addition to hormone receptor status. Tissue sections were stained immunohistochemically for Ki67 nuclear antigen, estrogen, progesterone and Her2/neu receptors using an automated Dako machine (Dako Denmark. There was a significant inverse relationship of Ki67 levels with ER and PR, while values were directly proportional to the tumor grade and Her2/neu status. No significant association was found between Ki67 and size of tumor or nodal status. Ki67 immunoexpression may offer an independent predictive tumor marker and for routine application in cases of breast cancer.

High immunoexpression of Ki67, EZH2, and SMYD3 in diagnostic prostate biopsies independently predicts outcome in patients with prostate cancer

IntroductionOvertreatment is a major concern in patients with prostate cancer (PCa). Prognostic biomarkers discriminating indolent from aggressive disease in prostate biopsy are urgently needed. We aimed to evaluate the prognostic value of Ki67, EZH2, LSD1, and SMYD3 immunoexpression in diagnostic biopsies from a cohort of PCa patients with long term follow-up. Materials and methodsA series of 189 consecutive prostate biopsies diagnosed with PCa (1997–2001) in a cancer center was included in the study, with follow-up last updated in November 2016. Biopsies were reviewed and graded according to 2016 WHO criteria. Immunohistochemistry was performed in the most representative block. Nuclear staining was assessed using digital image analysis. Study outcomes included disease-specific, disease-free, and progression-free survival. Statistical analysis was tabulated using SPSS version 22.0. Survival curves and hazard ratios (HRs) were estimated using Kaplan-Meyer and Cox-regression models, respectively. Statistical significance was set at P<0.05. ResultsThe proportion of patients who completed the study was 177/189 (94%). In univariable analysis, high Ki67, EZH2, and SMYD3 immunoexpression associated with significantly worse disease-specific survival (HR = 1.86, 95% CI: 1.05–3.29; HR = 1.87, 95% CI: 1.10–3.27; HR = 2.68, 95% CI: 1.02–7.92). In multivariable analysis, the 3 biomarkers displayed significantly worse DSS adjusted for CAPRA score (HR = 1.78, 95% CI: 1.01–3.16; HR = 1.93, 95% CI: 1.12–3.32; HR = 2.71, 95% CI: 1.04–7.10). Among patients with low/intermediate risk CAPRA score, high Ki67 immunoexpression identified those more prone to experience disease recurrence (HR = 9.20, 95% CI: 1.27–66.44) and progression (HR = 2.97, 95% CI: 1.05–8.43). ConclusionsHigh Ki67, EZH2, and SMYD3 immunoexpression, adjusted for standard clinicopathological parameters, independently predicts outcome in patients with PCa, at diagnosis. This might assist in discriminating indolent from aggressive PCa, improving treatment selection.