Purpose: Centromere protein H (CENP-H) and Ki67 are overexpressed in some malignancies, but whether they are predictors of survival after primary resection for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Methods: We assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens collected between March 2003 and March 2005 for analysis by clinical characteristics. The Kaplan-Meier method was used to analyze relapse-free survival and logistic multivariate regression to determine risk factors of relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H in HSCC cells. Results: Overall, 50 (44.6%) HSCC specimens showed upregulated CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein level was associated with advanced cancer stage and alcohol history (P=0.012 and P=0.048, respectively) but an increased Ki67 protein level only with advanced cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short relapse-free survival (P<0.001 or P=0.009, respectively) and were independent predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell apoptosis in vitro. Conclusions: Upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in HSCC. These factors may be predictors of a relapsing phenotype in HSSC cases.
Min Hyun-Jung;Kim Kyung-Rae;Park Chul-Won;Lee Hyung-Seok;Paik Seung-Sam;Oh Young-Ha;Tae Kyung
Korean Journal of Head & Neck Oncology
/
v.22
no.1
/
pp.8-14
/
2006
Objectives: The p53 tumor suppressor gene has a key role in cellular control mechanisms involving apoptosis and DNA repair, leading to the G1 arrest following DNA damage. Its mutation is one of the most frequent alterations in human cancers. Ki-67 is identified in replicating cells of both benign and malignant lesions, so it can be the predictor of proliferative activity. The aim of this study is to evaluate the expression of p53 and Ki-67 in salivary gland tumors. Materials and Methods: Immunohistochemical analysis was used to detect expression of p53 and Ki-67 in paraffin-embedded samples from 31 benign and 27 malignant salivary gland tumors. Results were analyzed between benign and malignant tumors and compared with the clinical parameters such as stage and recurrence in malignant tumors. Results: p53 overexpression was detected in 19.6% of benign tumors and 40.7% of malignant tumors, but there was no statistical significance. p53 was significantly expressed in Warthin's tumor(45.5%) compared with pleomorphic adenoma(5.9%). Only 5.9% of pleomorphic adenoma were positive for p53, while 60% of carcinoma ex pleomorphic adenoma were positive for p53. Ki-67 was expressed in 3.2% of benign tumors and 51.9% of malignant tumors, which showed significant higher expression in malignant tumors. In malignant tumors, p53 and Ki-67 expressions bore no correlation to stage and recurrence. Conclusion: p53 overexpression is not associated with the progression of malignant tumors, and Ki-67 overexpression can be used as biologic indicator of malignant salivary gland tumors.
We investigate the effect of phosphorous content on the microstructure and magnetic properties of Fe83.2Si5.33-0.33xB10.67-0.67xPxCu0.8 (x = 1-4 at.%) nanocrystalline soft magnetic alloys. The simultaneous addition of Cu and P to nanocrystalline alloys reportedly decreases the nanocrystalline size significantly, to 10-20 nm. In the P-containing nanocrystalline alloy, P atoms are distributed in an amorphous residual matrix, which suppresses grain growth, increases permeability, and decreases coercivity. In this study, nanocrystalline ribbons with a composition of Fe83.2Si5.33-0.33xB10.67-0.67xPxCu0.8 (x = 1-4 at.%) are fabricated by rapid quenching melt-spinning and thermal annealing. It is demonstrated that the addition of a small amount of P to the alloy improves the glass-forming ability and increases the resistance to undesirable Fex(B,P) crystallization. Among the alloys investigated in this work, an Fe83.2Si5B10P1Cu0.8 nanocrystalline ribbon annealed at 460℃ exhibits excellent soft-magnetic properties including low coercivity, low core loss, and high saturation magnetization. The uniform nanocrystallization of the Fe83.2Si5B10P1Cu0.8 alloy is confirmed by high-resolution transmission electron microscopy analysis.
Objective : We conducted this study with the aim of predicting the biological behavior of meningiomas, and determining the benefits of associating histological subtype and grade with the expression of proliferative markers and tumor suppressor proteins. Methods : The study included 29 patients with primary intracranial and intraspinal meningioma diagnosed in the pathology laboratory of Konya City Hospital between January 2014 and December 2020. Clinicopathological characteristics of the patients including parameters such as age and gender were obtained from the hospital records. Histopathological findings were obtained by re-evaluating the preparations stained with Hematoxylin-Eosin, which were extracted from the archive, and by evaluating new sections obtained from paraffin blocks of patients stained with Ki67, p53, and p57 immunohistochemical stains. Results : A moderate correlation was found between tumor size and Ki67 proliferation index (PI) (p=0.003, r=0.530). There was no significant difference between grade I and grade II tumors in terms of p53 (p=0.184) and p57 (p=0.487) expressions. There were higher levels of Ki67 PI in grade II tumors. The histological subtypes of the tumor had no significant difference with Ki67 PI (p=0.018), p53 (p=0.662), and p57 (p=0.368) expressions. Conclusion : In order to obtain more definitive results, there is a need for studies, which are conducted with a greater number of patients and in multiple centers, and in which a long prospective follow-up is planned. The combination of histological, surgical, and imaging markers could make a more sensitive tool for predicting recurrence, and this could also be tested in future studies.
Background and objectives; Esophageal cancer is one of the most malignant tumors and has a poor prognosis. Many clinical studies have been tried for improving prognosis of esophageal cancer. Some clinical studies used molecular markers as the predictor of prognosis & the indicator for the choice of multimodality treatments. We investigated the relationship between some molecular markers, including p53 mutation, expression of bc12, Ki67 index, expression of E-Cadherin and the prognosis of esophageal cancer, Materials and Method; The materials used in this study were the tumor specimens from 72 esophageal cancer patients who underwent esophagectomy from 1987 to 2002 in our institute. The mutation of p53, expression of bc12, Ki67 index, and expression of E-cadherin were examined by using the tissue array and immunohistochemical staining method. The patients were subgrouped into higher Ki67 index group if the index was higher than 30. The patients were also subgrouped into grade 1(>90%), grade 2(50∼90%), grade 3 (10∼50%), and grade 4(<10%) according to the rate of E-Cadherin expression. We studied the relationship between the rates of immunohistochemical staining and the survival rate. Results: Seventy two tumor specimens from 72 patients were studied. (mean age ; 59.6 years, male female = 69 : 3) The histologic type of the specimens was all squamous cell carcinoma. The patient's number of stage IIA, IIB, and Ⅳ was 30, 37, and 7 respectively, Thirty patients were alive and overall 5 year-survival rate was 28%. The mutation of p53 was shown in 54.2% of the patients. Five year survival rates of negative and positive groups were 29% and 28% respectively.(p=0.4) Expression of bc12 gene was found in 13.9% of the specimens. Five year survival rates of negative and positive groups were 30% and 21%.(p=0.3) Higher Ki67 index was correlated to poorer differentiation.(p=0.05) Five year survival rates of higher and lower groups of Ki67 index were 47% and 30%.(p=0.15) Higher expression rate of E-Cadherin showed better differentiation.(p=0.04). However we couldn't find any survival differences between these 4 groups.(p=0.23) Conclusion; We could not find any molecular markers meaningful in the prognosis of esophageal cancer patients. We just found the tumor markers correlated to the differentiation of esophageal cancer. However, we knew that we need further study with some more samples to stratify other important prognostic factors of esophageal cancer.
Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is the second most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous. This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained from NB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blocks were constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMA sections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression of these markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB, one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%) tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High and moderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it was positively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI (mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relative correlation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapy was correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as a valuable marker for the prognosis of this tumor type.
Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.
The respiratory burst oxidase of neutrophils is a multicomponent enzyme, domant in resting cells, that catalyzes the reduction of oxygen to $O_{2}^{-}$ at the expense of NADPH. In the resting neutrophil, some of the components of the oxidase, including proteins p47 and p67, are in the cytosol, while the rest are in the plasma membrane. Recent evidence has suggested that at least some of the cytosolic oxidase components exist as a complex. The cytosolic complex with a molecular weight of ~240 kDa was found to bind to blue-agarose and 2',5'-ADP-agarose, which recognize nucleotide requiring enzymes. In order to identify the nucleotide binding component of the cytosolic complex we purified recombinant p47 and p67 fusion proteins using the pGEX system. Pure recombinant p47 was retained completely on 2',5'-ADP-agarose, whereas pure recombinant p67 did not bind to these affinity beads. On the basis of these results, we infer that p47 may contain the nucleotide binding site.
The objective of this study was to evaluate the acid and bile tolerance, bile salt hydrolase (BSH) activity, and cholesterol assimilation ability of lactic acid bacteria isolated from mustard leaf kimchi. MLK11, MLK22, MLK27, MLK41, and MLK67 were relatively acid- and bile-tolerant strains, with more than $10^5$ CFU/ml after incubation in simulated gastric juice and intestinal fluid, while MLK53 was the most sensitive strain to acid and bile. Strains MLK22 and MLK67 deconjugated the highest level of sodium glycocholate with more than 3.5 mM of cholic acid released, while deconjugation was lowest by strains MLK13 and MLK41 which released only 1.35 mM and 1.16 mM, respectively. Specially, strains MLK22 and MLK67 showed higher deconjugation of sodium glycocholate compared to sodium taurocholate and conjugated bile mixture. Although strains MLK22 and MLK67 exhibited maximal BSH activity at the stationary phase, MLK22 had somewhat higher total BSH activity compared to MLK67 towards both sodium glycocholate and sodium taurocholate. Meanwhile, cholesterol removal varied among tested strains (p<0.05) and ranged from 5.22 to 39.16 ${\mu}g$/ml. Especially, MLK67 strain assimilated the highest level of cholesterol in media supplemented with 0.3% oxgall, cholic acid, and taurocholic acid (p<0.05). According to physiological and biological characteristics, pattern of carbohydrate fermentation, and 16S rDNA sequence, strain MLK67 that may be considered as probiotic strain due to acid and bile tolerance and cholesterol-lowering effects was identified as Pediococcus pentosaceus MLK67.
Ameloblastoma is a common odontogenic benign tumor of the jaw bone. However, it might be albe to infiltrate into the adjacent tissue, causing bony destruction and high recurrent rate. The aim of the study is to understand the biologic behavior of recurred ameloblastoma through immunohistochemical study. The PCNA, Ki-67, p53 and cytokeratin 17, cytokeratin 18 antibody staining were used. There was significant difference of positive reaction between non-recurred ameloblastoma and recurred ameloblastoma in PCNA and cytokeratin 17. There were no significant difference of positive reaction between non-recurred ameloblastoma and recurred ameloblastoma in p53, Ki-67 and cytokeratin 18. From the above results, it is suggested that the recurrence of ameloblastoma is related to positive reactions of PCNA and cytokeratin 17 and the progonsis of the recurrence of ameloblastoma is able to be predicted by using PCNA and cytokeratin 17.
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