Percentage Of MIB-1 Positive Cells Research Articles

Correlation of Ki67 Expression with Hormone Receptors, Human Epidermal Growth Factor Receptor-2 (HER-2) Status, P53 Mutation and Clinicopathological Characteristics in Pathologic Specimens of Breast Cancer Patients

Background: Breast cancer is the main cause of cancer in women and the second cause of ma­lignancy deaths. Ki-67 is one of the molecular markers used to evaluate cancer prognosis along with other factors such as age, tumor size, lymph node involvement, estrogen receptor (ER), progesterone receptor (PR), P53, human epidermal growth factor receptor-2 (HER-2), histolog­ical and nuclear grades. This study was aimed to evaluate the correlation of KI-67 expression with some biomarkers and clinico-pathological characteristics in breast cancer patients. Mate­rials and Methods: A total of 513 cases (all female) aged 40- 80 years, were randomly selected from patients who were admitted in two centers affiliated with Tehran University of Medical Sciences (Buo-alli and Kasra hospitals) over a 7-year period (2010-2015). Assessment of tumors for HER-2, P53, ER PR, pathological type and histologic grade was performed. Ki-67 labelling index (Ki-67LI) was defined as the percentage of MIB1-positive cells among a total number of 1,000 malignant cells at high-power magnification (×400). Results: Our study showed that age, ER and PR status were negatively correlated with Ki-67LI (P<0.05). Moreover, number of lymph nodes involved, HER-2, P53 and nuclear grades had a positive correlation with Ki-67LI (P<0.05), whereas, tumor size and histological grade showed no significant correlation with Ki-67LI (P =0.195 and P=0.721, respectively). Conclusion: Results of our study and other studies confirm that the expression of Ki-67 is significantly associated with ER, PR, HER-2 and P53 status. On the other hand, Ki-67 relationship with clinical characteristics such as age, tumor size and lymph node metastasis is not completely established and needs further research.[GMJ.2016;5(2):90-97]

18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair

BackgroundWe observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the ‘excess’ uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL).MethodsWe performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed.Results18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively.ConclusionsThis is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.

Prognostic relevance of MAPK expression in glioblastoma multiforme

The objective of this study was to determine the immunoexpression pattern of the mitogen-activated protein kinase (MAPK), and related signalling proteins [protein kinase C (PKC), phospholipase Cgamma (PLCgamma)], in glioblastoma multi-forme, and to investigate their prognostic value. Paraffin-embedded biopsy samples from 26 patients [13 patients with long-term survival (LTS; N=13; median 28 months, range 13-76 months), and, for comparison, 13 patients with short-term survival (STS; N=13; median 7 months, range 1-12 months)] were investigated for the immunoexpression of MAPK, the activated pMAPK, PKC, PLCgamma, EGFR, and PTEN. Additionally, the MIB-1 proliferation index was determined. The immunoexpression pattern were related to clinical data, including analysis of their prognostic value using the Cox-proportional hazard model. No significant differences were found between STS and LTS in terms of age, Karnofsky performance status, and treatment. Whereas EGFR expression did not differ between STS and LTS and does not influence survival, expression of MAPK and activated pMAPK was significantly correlated with survival time. The percentage of pMAPK expressing cells correlated strongly with the percentage of MIB-1 positive cells. Furthermore, survival in patients with tumors expressing PKC or PLCgamma was significantly shorter. No differences were found for PTEN expression. Our findings indicate that the MAPK pathway is correlated with proliferation in gliomas, and that patient subgroups exist, in which expression of MAPK-related signalling proteins (PKC, PLCgamma) is associated with poorer prognosis. These patient subgroups may benefit from additional chemotherapeutic agents which specifically inhibit these signalling proteins.

Effects of oral contraceptives on breast epithelial proliferation.

The association between oral contraceptive (OC) use and breast cancer is not fully understood. Estrogen is a known mitogen to breast epithelial cells, but there is still a controversy about the effect of added progestogens. Fine needle aspiration (FNA) biopsies were used to assess epithelial proliferation in normal breast tissue from 106 healthy premenopausal women with and without oral contraceptives. In 26 women biopsies were performed before and after 2 months of OC use. Proliferation, expressed as percentage of Ki-67/MIB-1 positive cells, was correlated to endogenous progesterone, androgenic/anabolic compounds and exogenous progestogen. We found a higher proliferation (p = 0.03) in OC users compared to non users, with mean values of 4.8% and 2.2%, respectively. There was a positive correlation between proliferation and progesterone levels in non-users and with serum levonorgestrel concentrations in women using OCs containing this progestogen (rs = 0.43, p = 0.02). Women using OCs had significantly lower serum androgen levels compared to naturally cycling women and free testosterone levels displayed an inverse relation to breast epithelial proliferation. There was a marked variation in the response to exogenous sex steroids. In certain women after 2 months of OC use, the percentage of MIB-1 positive cells was as high as 40-50%. The results add to the growing evidence that progestogens may be mitogenic in breast tissue. Increased proliferation during hormonal contraception should be regarded as an unwanted and potentially hazardous side effect. Efforts should be made to define hormonal contraceptive regimens which minimize breast epithelial proliferation and to identify those women with the most pronounced proliferative response.

Evaluation of apoptosis as a prognostic factor in myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hypercellular bone marrow. This is thought to be as a result of the apoptosis of haematopoietic bone marrow cells resulting in ineffective haematopoiesis. To clarify the relationship between prognosis and apoptosis and/or cell proliferation in the bone marrow, we studied 51 cases with MDS. Bone marrow biopsies were stained immunohistochemically for MIB-1 (marker for proliferating cells) and CD34 (marker for stem cells). Apoptosis was visualized by detection of DNA fragmentation using TdT incorporation of nucleotides on 3' ends of DNA (TUNEL technique) and expressed as the apoptotic rate. MDS patients included 32 with refractory anaemia (RA), one RA with ringed sideroblasts (RARS) patient, seven RA with excess of blasts (RAEB) patients, eight patients with RAEB in transformation (RAEB-t) and three patients with chronic myelomonocytic leukaemia (CMMoL). In addition, we also studied six cases with acute myeloid leukaemia (AML) arising from MDS (AML-MDS) and ten control subjects. Fatal pancytopenia was the cause of death in 19 out of 51 patients. The apoptotic rate was higher in MDS patients (5.5%) than in control subjects (0.6%) and AML-MDS patients (0.4%). The percentage of MIB-1 positive cells was higher in MDS and AML-MDS than in control. The percentage of CD34-positive cells was higher in AML-MDS, RAEB, RAEB-t and CMMoL patients than control subjects and RA patients. Our findings indicate the activation of both the proliferative and apoptotic rates in MDS. Poor prognosis correlated significantly with higher apoptotic rates, but not with percentages of MIB-1 and CD34-positive cells. Our results suggest that apoptosis might be a useful prognostic factor and inhibition of apoptotic mechanisms may induce leukaemic transformation in MDS.

Proliferation assessment in breast cancer: a double-staining technique for AgNOR quantification in MIB-1 positive cells especially adapted for image cytometry

There are two ways of measuring the cell proliferation. The first one consists of quantifying the number of cycling cells with the help of antibodies directed against cells either in G1, S, G2 or M phase. The second way is to assess the cell cycle duration by the quantification of AgNOR proteins. Measuring both the features on the same slide represents an attractive way to tackle the proliferating activity of a cell culture or a tumor. Here, we propose a MIB-1 and AgNOR double staining method especially adapted to image cytometry measurement, using MIB-1 antibody coupled to FITC in order to avoid the thresholding problems encountered with such a multilabeling technique. We have applied this new method on a series of 39 breast cancer cases, with at least 4 years follow-up, in order to determine the prognosis significance of this measurement. MIB-1 alone is not linked to prognosis, while the global mean AgNOR area is significantly linked to prognosis in terms of development of visceral metastasis or death. However, the global mean AgNOR area is insufficient to determine the time limit of appearance of metastasis or relapse. Our results clearly demonstrate that a high mean AgNOR area within a cell population having a high MIB-1 index can discern tumors with a high metastatic potential. By multiplying AgNOR area by the percentage of MIB-1 positive cells we calculate the proliferative activity, P, which brings very important information concerning the time limit of relapse.

Utility of proliferation-associated marker MIB-1 in evaluating lesions of the uterine cervix.

Various cervical lesions at times may be difficult to distinguish from one another on routine hematoxylin and eosin stains, and immunostaining for the proliferation-associated antigen Ki-67, using monoclonal antibody MIB-1, can aid their distinction. The reduced MIB-1 expression in atrophy and increased MIB-1 expression in dysplasia permits easy distinction between these conditions. Presence of MIB-1 in more than 15% of basal cells and/or in surface half of the epithelium favor a diagnosis of condyloma over squamous metaplasia or inflammatory changes. Normal endocervix shows MIB-1 positivity in less than 10% of the cells, but usually in more than 20% of cells in cervical adenocarcinoma. With increasing grade of dysplasia, the percentage of MIB-1 positive cells is increased, and positive cells are seen in the higher levels of the epithelium. Presence of more than 20% MIB-1 positive cells in Pap smears showing atypical cells of uncertain significance is associated with a diagnosis of dysplasia on subsequent biopsies. Cauterized tissues with dysplasia show MIB-1 expression similar to adjacent noncauterized dysplastic areas. MIB-1 expression is, therefore, useful in evaluating various cervical lesions.

Mitotic granuloma annulare: a clinicopathologic study of 20 cases.

The finding of mitotic figures in granuloma annulare (GA) has not been emphasized in the literature. We describe 20 cases of a cellular, mitotically active variant of GA; we defined this group as cases having > or = 1 mitosis per 10 hpf. Clinically, the lesions could not be distinguished from typical, localized GA: there were 9 males and 11 females with a mean patient age of 49 +/- 15 years (mean +/- SD), compared to 45 +/- 20 years in a randomly selected control group of 60 patients with GA, and no unusual sites of predilection were noted. Histologically, a classic, palisading granuloma pattern predominated (18/20 cases). Lesions were located in the mid-dermis and tended to be more cellular than typical GA. The histiocytes comprising the lesion often had enlarged nuclei and prominent nucleoli. The number of mitoses per 10 hpf was 3.0 +/- 1.5 (range 1.0-7.2), control group 0.3 +/- 0.5; occasional atypical mitotic figures were observed. The proliferative nature of these lesions was confirmed using MIB-1 staining; the percentage of MIB-1 positive cells ranged from 5%-29% (mean 15 +/- 6%). Mitotic GA must be distinguished histologically from neoplastic processes, in particular epithelioid sarcoma. We conclude that histiocytes in clinically typical GA can exhibit an increased mitotic rate. Recognition of this variant is important in order to avoid overdiagnosis of a malignant condition.

664 Flow cytometrically determined S-phase fraction is a stronger prognostic factor in node-negative breast cancer than immunohistochemically detected MIB1 (KI-67)

The proliferation markers, S-phase fraction (SPF) and MIB1, were evaluated in 90 primary node-negative breast carcinomas. SPF was determined flow cytometrically using an improved Hedley protocol for release of pure nuclei from formalin-fixed, paraffin-embedded sections. SPF analysis was performed using the ModFit software program (Verity, Maine, U.S.A.). MIB1 immunostaining (Dianova, Hamburg, Germany) was performed on adjacent paraffin sections using APAAP. The percentage of MIB1 positive cells was calculated in 500 randomly chosen tumor cells. Median follow-up was 34 (9–72) months. An optimal cutoff of 8% SPF was found using isotonic regression analysis: 61 (68%) tumors had low (≤ 8%) and 29 (32%) high (> 8%) SPF. The optimal cutoff for MIB1 was 25%: 75 (83%) tumors had a low (≤ 25%) and 15 (17%) a high (> 25%) MIB1 staining percentage. MIB1 was significantly correlated to grading (P = 0.018) and medullary histological tumor type (P