Ki‑67 Expression in Oral Potential Malignant and Malignant Lesions and Correlation of Mitotic Index with MIB‑1 Labeling Index

Introduction: Oral cancers are the most serious health issues in underdeveloped countries such as India and considered as the main cause of death. Among them, oral squamous cell carcinoma is the most common type (90%) of all malignancies. Various oral potential malignant lesions (OPMLs) can transform into malignancies. This study was conducted to determine the significance of Ki‑67 expression in oral potential malignant and malignant lesions (MLs) as well as correlation of mitotic index (MI) with MIB‑1 labeling index (LI) in these lesions. MaterialsandMethods: The study was performed on 60 cases in a tertiary care center over a period of 2 years. Ki‑67 expression, MI and MIB‑1 LI were calculated and correlated. Results: In the studied population, there were 49 (81.7%) males and 11 (18.3%) females. The mean age was 46.60 ± 9.94 (23–68 years), with majority of patients in 41–60 years of age group (46/60 cases). Anterior 2/3rd tongue is the most affected site, presented ulcer as the most common lesion. Smoking, tobacco, and betel nutchewing addiction were presented in 72% of the patients. Among 60 cases, 45 (75%) were OPMLs, while 15 (25%) cases were MLs. MI increases in OPMLs and MLs and comparison was significant (P < 0.01). MIB‑1 LI was significant (P < 0.01) on comparison to dysplasia III and MLs. A positive correlation (0.01) was established between MI and MIB‑1 LI of OPMLs and MLs. Conclusion: Ki‑67 expression was found correlated with the progression of disease from OPMLs to MLs. Therefore, it is considered a proliferative marker that corresponds with disease progression. Both proliferative indices (MI and MIB‑1 LI) are positively correlated

Role of Ki 67 Labelling Index as an Adjunct to Histopathological Diagnosis for Grading of CNS Tumours

The Central Nervous System tumours are unique as they arise from specialized tissue. CNS tumours constitute a wide range of neoplasm that differs in their location, age distribution, extent of invasiveness, morphological features and tendency for progression. We wanted to evaluate the traditional morphological data with knowledge on the prognostication marker Ki 67 antibody in evaluating tumour grade and prognosis of CNS neoplasm.METHODSThis is a cross section study carried out between March 2015 and September 2016 in histopathology department of Dhiraj Hospital on 50 cases of CNS tumours. Immunolabelling of all biopsies was done by horse radish peroxidase technique using rabbit monoclonal antibody to Ki 67 (clone SP 6) (Thermo Scientific, USA). Ki 67 immune positive labelling index was obtained for each tumour and correlated with mitotic labelling index obtained by conventional morphological grading as per WHO 2007 classification.RESULTSIn our study of CNS tumours, all age groups were studied. The mean Ki 67 labelling index (LI) values +/-SD for WHO Grade I tumours were- meningiomas (10) 3.85 (+/1.97) %, schwannoma (3) -3.0 (+/-2.97) %, pituitary adenoma (1) 0.6, craniopharyngioma (1) -1.1% and ependymoma (6) 2.62 (+/-0.60) %. WHO Grade II tumours- atypical angiomatous meningioma (1) -2%, atypical mucinous meningioma (2) -6.15 (+/-1.06) %, gemistocytic astrocytoma (1) -12; pleomorphic xanthoastrocytoma (2) -4.3 (+/-0.99) %, astrocytoma grade ii (2) -3.3 (+/-0.71) %, oligodendroglioma grade ii (4) - 3.9 (+/-0.88) %. WHO grade III tumours- anaplastic astrocytomas (5) -6.82 (+/-2.17) %, anaplastic oligoastrocytoma grade iii (1) -10.8 %. who grade iv-glioblastomas (7) -18.44 (+/-3.97) %; medulloblastomas (1) 20%, metastatic tumour (3) -36 (+/- 22.16) %. In our study, the mean Ki 67 LI (± SD) values for grade II, III and IV glioma is as follows: 4.76 (+/-2.83) %, 7.48 (+/-2.53) % and 18.44 (3.97) % respectively.CONCLUSIONSThis study shows that Ki 67 LI serves as an essential clinical prognostic proliferation marker of particular importance in cases with lower grade histology of Grade II & Grade III astrocytomas, Grade II & Grade III oligodendrogliomas. Ki 67 LI is important in determining benign, atypical and malignant meningiomas, non-invasive and invasive pituitary adenomas.

Notch signaling in the collecting duct regulates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction in mice

BACKGROUND/AIMS: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. METHODS: Mib1-floxed mice (Mib1f/f ) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice (Mib1f/f :AQP2-Cre+). Unilateral ureteral obstruction (UUO) was performed, and mice were sacrificed 7 days after UUO. RESULTS: After performing the UUO, renal tubulointerstitial fibrosis and the expression of transforming growth factor β were markedly enhanced in the obstructed kidneys of Mib1f/f mice compared with the sham-operated kidney of Mib1f/f mice. These changes were shown to be even more pronounced in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in those of the Mib1f/f mice . Furthermore, the number of TUNNEL-positive cells in renal collecting duct was higher in the obstructed kidneys of Mib1f/f :AQP2-Cre+ mice than in the kidneys of Mib1f/f mice. CONCLUSIONS: Notch signaling in the renal collecting duct plays an important role in the regulation of renal tubulointerstitial fibrosis and apoptosis after UUO.

Research progress on hyalinizing trabecular tumor / 中国肿瘤临床

Hyalinizing trabecular tumor (HTT) is a primary thyroid tumor discovered 20 years ago. This tumor is usually misdi-agnosed as papillary thyroid carcinoma because of their many similar nuclear features. Although controversy has focused on the malig-nant potential of HTT, results show that this tumor has a favorable clinical prognosis. Improving the preoperative diagnosis of HTT can reduce the scope of operation because misdiagnosis before or during surgery may lead to unnecessary total thyroidectomy. This study re-viewed the pathology, diagnosis, therapy, and prognosis of HTT.

Clinical Features and Treatment Outcome of Chordoid Meningiomas in a Single Institute

OBJECTIVE: Meningioma is the second most common primary central nervous system neoplasm. In contrast, chordoid meningioma is rare; due to the paucity of cases, little is known about its clinical features or treatment outcomes. The objectives of this study were to describe the clinical characteristics and outcomes for patients with chordoid meningioma. METHODS: In total, 16 patients, with newly diagnosed chordoid meningioma who underwent surgical excision between 1999 and 2012 were included. We retrospectively evaluated the medical records, radiological findings, and pathological findings. The median follow-up period was 56.5 (range, 3-170) months. The MIB-1 labeling index ranged from 1 to 26.60% (median, 5.04). RESULTS: Simpson grade I, II, and III resections were performed in four, nine, and three patients, respectively. The overall recurrence rate was 37.5%. Overall progression-free survival (PFS) after resection was 94.7 months (95% CI=62.9-126.6). Of the 4 patients with Simpson grade I resection, recurrence occurred in one patient. Among the Simpson grade II and III resection groups, eight patients underwent adjuvant radiation therapy and they showed significantly longer PFS (121 months, 95% CI=82.1-159.9) than the patients who underwent surgery alone (40.5 months, 95% CI=9.6-71.3) by the log-rank test (p<0.05). CONCLUSION: Chordoid meningiomas are difficult to manage and have a high rate of recurrence. Complete resection of the tumor is a key determinant of better outcomes. Adjuvant radiation therapy is recommended, eparticulary when Simpson grade I resection was not achieved.

Immunohistochemical expression of MIB-1 and PCNA in precancerous and cancerous lesions of uterine cervix.

BACKGROUND AND OBJECTIVE: The present study was done to analyze the immunoexpression of diagnostic markers (MIB-1: molecular immunology borstel and PCNA: proliferating cell nuclear antigen) in grading cervical intraepithelial lesion (CIN) and squamous cell carcinoma (SCC) in cervix. SETTING AND DESIGN: Total 150 cervical biopsies were divided into four groups respectively; Group I-Normal (n = 32), Group II- CIN (n = 60), Group III- SCC (n = 44), Group IV- CA cervix (n = 14) respectively. MATERIALS AND METHODS: These biopsies were stained with monoclonal antibodies by streptavidin-- biotin method. Mean labeling index was calculated and grading was performed using the I--III scoring system. STATISTICAL ANALYSIS: Findings were correlated with age and menopausal status. Statistical analysis was done by using student sample‘t’ test and analysis of variance (ANOVA) by SPSS 10 package. RESULTS: MIB-1 immunostaining was positive in 112/150 (74.6%) cases and PCNA in 118 /150 (78.6%) cases. Labeling indices showed linear progression from normal to CIN to SCC to cancer lesion. Few cases of low-grade CIN lesion had high proliferative index. A significant positive correlation was found between age and PCNA and MIB-1 values (P < 0.05) when comparison was made for all the cases. CONCLUSION: These markers may be useful in identifying low-grade CIN lesion with high proliferative index. These cases should be kept for follow up studies so that proper intervention can be taken at an early stage. This method is simple and cost effective and can easily be done in formaline-fixed paraffin embedded tissues in a clinical laboratory for grading CIN and SCC lesions in cervix.

Cell proliferation markers in the transplanted canine transmissible venereal tumor / Marcadores de proliferação celular no tumor venéreo transmissível canino transplantado

Adult male mongrel dogs were subcutaneously transplanted with the canine transmissible venereal tumor (TVT) on the hypogastric region. Twelve specimens of tumors were collected, half during the proliferative phase and the other half during the regressive phase. Fragments of the tumor were fixed in 10 percent buffered formalin and routinely processed for light microscopy. Sections of 4µm were stained by Schorr or AgNOR or either immunostained for MIB1 (Ki67). Schorr stain, AgNOR and MIB1 showed an increased proliferative activity through mitotic index, nuclear argyrophilic protein stain and cycling tumoral cells in the growing tumors, respectively. All of the three cell proliferation markers were able to distinguish the TVT in both evolution phases. MIB1 monoclonal antibody was the best in the morphologic evaluation of growth and regression of TVT. This resulted in higher values than AgNORs counting and mitotic index. MIB1 immunostaining was the most effective parameter of the proliferative activity of TVT. However, a significant correlation has been detected only between mitosis counting and AgNORs.

Cães machos, adultos, mestiços, foram transplantados com células do tumor venéreo transmissível canino (TVTC), na região hipogástrica. Foram coletados doze espécimes do TVTC, sendo metade durante a fase proliferativa e metade durante a fase regressiva. Fragmentos do tumor foram fixados em formol a 10 por cento, tamponado e processado rotineiramente para microscopia de luz. Secções de 4µm foram coradas pelo Shorr, ou pela AgNOR, ou ainda, imunocorado para MIB 1 (Ki67). As colorações pelo Shorr, AgNOR, ou MIB 1 mostraram um aumento do índice mitótico, coloração da proteína argirofílica nuclear e células tumorais ciclando em tumores em crescimento, respectivamente. Todos os três marcadores de proliferação celular foram capazes de distinguir o TVTC em ambas as fases de evolução. O anticorpo monoclonal MIB 1 foi o melhor na avaliação morfológica, de crescimento e regressão do TVTC. Isto resultou em um valor maior que a contagem de AgNOR e do índice mitótico. A imunomarcação com MIB1 foi o parâmetro mais efetivo da atividade proliferativa. No entanto, só foi observada uma correlação positiva entre a contagem de mitose e a AgNOR.

Frequency of Ki-67 (MIB-1) and P53 expressions among patients with prostate cancer.

Context: Prostate cancer is the most common malignant tumor in men. Tumor grade is one of the most important prognostic factors of prostate cancer. P53 and Ki-67 expressions have also been considered to be prognostic factors. Aims: This study was performed to investigate the frequency of these proteins expression and compare the obtained results with Gleason's grading. Settings and Design: In this cross-sectional study, 49 paraffin blocks of prostate cancers were assessed. Tumor grade was determined according to the Gleason's criteria. Materials and Methods: Ki-67 and P53 expressions were determined by immunohistochemical staining. Statistical Analysis: The obtained results were analyzed and evaluated using Spearman's statistical test (SPSS version 15). Results: Three out of 49 (6.1%) cases were well differentiated, 21 (43%) moderately differentiated and 25 (51%) were poorly differentiated. P53 was negative in all well-differentiated cases. Ki-67 was negative in 14 cases (28%) including all well-differentiated tumors. Among moderately and poorly differentiated tumors Ki-67 was negative in eight (38%) and three (12%) of cases, respectively. A statistically significant relation was observed between the increased Ki-67 labeling index (LI) and increased Gleason's grade. Conversely, no statistically significant relation was found between P53 expression and increased Gleason's grade. Conclusions: According to the findings of this study, it seems that Ki-67 can be used as a prognostic factor for prostate cancer. On the other hand, the probable relation between P-53 and prostate cancer prognosis requires further studies.

Practical value of MIB-1 index in predicting behavior of astrocytomas.

Background : The MIB-1 labeling index (LI) has proved to be useful in assigning grading and prognosis to astrocytomas. The purpose of our study was to analyze the utility of MIB-1 LI in differentiating astrocytomas of varying grades and the possible relationships of MIB-1 LI with clinical parameters like age and sex. We also wanted to study the prognostic role of MIB-1 index in predicting behavior of astrocytomas. Materials and Methods : Our study included 145 patients with astrocytic tumors of varying grades. Immunolabeling for all patients was done using MIB-1 antibody. Survival data could be obtained for 64 patients. A Mann-Whitney U test was used to test the difference in MIB-1 LI between different histological grades. The univariate analysis was done by the Kaplan-Meier method, and the multivariate analysis for survival was performed using the Cox proportional hazard model. Results : Significant differences were noted in mean MIB-1 LI of high-grade and low-grade diffuse astrocytomas. MIB-1 LI did not vary significantly with age and sex. Univariate analysis showed favorable prognostic factors for low histopathological grade, young patient age and low MIB-1 LI; however, multivariate analysis showed that only histopathological grade had independent prognostic significance. Conclusions : Our study proves that MIB-1 LI is not dependent on factors like age and sex and is solely dependent on histological grade. Though the average level of MIB-1 LI varies considerably in the different grades of astrocytomas, considerable overlap can be observed between them. MIB-1 LI is a very useful adjunct to the histopathological diagnosis and can be of great help in situations where the clinical and radiological findings do not correlate with histological diagnosis.

Multi-focal Myxopapillary Ependymoma in the Lumbar and Sacral Regions Requiring Cranio-spinal Radiation Therapy: A Case Report

Ependymomas are uncommon tumors that arise in the brain, spinal cord or cauda equina. Myxopapillary ependymomas is located exclusively in the conus medullaris or cauda equina, or film terminale region. In most myxopapillary ependymomas, the histological examination reveals low mitotic activity that is associated with a low MIB-1 labeling index (LI). The prognosis is generally favorable, when the appropriate treatment, including a total resection, is performed. The authors encountered a 39-year-old man with multifocal type of myxopapillary ependymomas compressing the cauda equina from the L2 to L3 level and L5-S1 level. A subtotal resection of the tumor was carried out. The histological examination revealed extremely high mitotic activity with a MIB-1 LI of 9.1%. Therefore, cranio-spinal radiation was added after surgery. The postoperative course was uneventful over the 3.5 year follow-up period.

p16INK4A and MIB-1: An immunohistochemical expression in preneoplasia and neoplasia of the cervix.

Aim: To evaluate the potential of p16INK4A and MIB-1 and to compare the expression and interrelationship of these markers in cervical preneoplasias and neoplasias. Materials and Methods: Immunohistochemical analysis of p16 and MIB-1 was performed in n = 63 tissue sections and by matching the corresponding Papanicolaou smears. Staining intensity for p16 was determined using the 0-3 grading system. For MIB-1, labelling indices (LI) were calculated and grading was performed using the I-III scoring system. Results: No positive staining of p16 was observed in the normal cervical epithelium. With increasing severity of cervical intraepithelial neoplasias (CIN), the p16 expression increased progressively. Significant up-regulation of p16 was observed in carcinoma cervix. MIB-1 LI was observed to increase with increasing grades of CIN, and significant overexpression of MIB-1 was observed in carcinoma cervix. Correlation between grades of p16 and that of MIB-1 among cervical neoplasias showed an increasing p16 expression with consistently increasing MIB-1 LI in the groups of increasing severity. Conclusion: This pattern of overexpression of p16 and MIB-1 demonstrate their use as a diagnostic marker for cervical neoplastic lesion. Therefore, p16 and MIB-1 markers in tissue sections can be used as an adjunct to definitively diagnose preneoplastic and neoplastic lesions in the cervix.

Utility of tissue microarrays MIB-1 for profiling prognostic biomarkers in clinically localized prostate cancer / Expressão imuno-histoquímica do MIB-1 como fator prognóstico em pacientes com adenocarcinoma de próstata localizado

INTRODUCTION AND OBJECTIVE: To analyze the immuno-histochemical expression of MIB-1 marker as a prognostic factor in patients with localized prostate neoplasia. METHODS: Analysis of 100 cases of patients with localized prostate neoplasia who underwent curative surgery from January 2000 to December 2006. The customary histological preparation was carried out, followed by immunohistochemical reaction to detect MIB-1 protein accumulation and statistical analysis. RESULTS: There was a larger proportion of negative expression for MIB-1 marker (63.0 percent, p < 0.0001). Patients with positive expression (MIB-1 positive) had higher PSA (PSA > 10 ng/dl) (p = 0.010), higher Gleason score (> 7) (p = 0.0003) and pathological stage pT2c (p = 0.001). In the comparison of variables, it was noticed that patients with positive expression had a higher mean PSA (p = 0.031), higher Gleason score (p < 0.0001), longer follow-up (p = 0.037), larger area of vascular proliferation (p < 0.0001) and higher proportion of tumor in relation to normal area (p = 0.012). CONCLUSION: MIB-1 proved to be a prognostic factor comparable to PSA, Gleason and staging.

INTRODUÇÃO E OBJETIVO: Analisar a expressão imuno-histoquímica do marcador MIB-1 como fator prognóstico em pacientes com neoplasia de próstata localizada. MÉTODOS: Análise de cem casos de pacientes portadores de neoplasia prostática localizada submetida a cirurgia curativa no período de janeiro de 2000 a dezembro de 2006. Realizou-se o preparo histológico habitual seguido de reação imuno-histoquímica para a detecção do acúmulo da proteína MIB-1 e análise estatística. RESULTADOS: Obteve-se maior proporção de expressão negativa ao marcador MIB-1(63 por cento, p < 0,0001). Os pacientes com expressão positiva (MIB1 positivo) apresentaram antígeno prostático específico (PSA) mais elevado (PSA > 10 ng/dl) (p = 0,01), escore de Gleason mais alto (> 7) (p = 0,0003) e estádio patológico pT2c (p = 0,001). Na comparação das variáveis observou-se que os pacientes com expressão positiva apresentaram PSA médio mais elevado (p = 0,031), escore de Gleason mais alto (p < 0,0001), maior tempo de seguimento (p = 0,037), maior área de proliferação vascular (p < 0,0001) e maior proporção de tumor em relação à área normal (p = 0,012). CONCLUSÃO: O MIB-1 mostrou-se um fator prognóstico comparável a PSA, Gleason e estádio.

Assessment of cell proliferation and prognostic factors in canine mammary gland tumors / Avaliação da proliferação celular e fatores prognósticos em tumores mamários caninos

Three methods for the analysis of cell proliferation, mitotic index/10 high-power fields (10 HPF), mitotic index/four sets of 10 HPF (40 HPF), and MIB-1 index were evaluated in a series of canine mammary gland tumors, as well as the possible correlation between them. Fifty-six canine mammary gland tumors, including 23 benign and 33 malignant, were studied. In addition, the prognostic impact of mitotic index/10 HPF, and histological malignancy grade were evaluated in 17 malignant tumors, being seven ductal and 10 metaplastic carcinomas. The three methods used to evaluate cell proliferation were correlated with the prognostic impact of mitotic index/10 HPF and histological malignancy grade. The results showed a strong association between mitotic figure counts and MIB-1 index (P<0.0001). A correlation was observed between mitotic count per 40 HPF and MIB-1, and between mitotic index per 10 HPF and 40 HPF (P<0.05). Moreover, histological malignancy grade and mitotic figure counts were excellent prognostic factors during three-year follow-up (P<0.05). There was a correlation between the three methods used for the evaluation of cell proliferation and prognostic factors as observed in human breast cancer studies.

Avaliaram-se três métodos de proliferação celular, índice mitótico/10 campos de grande aumento (10 CGA), quatro vezes 10 CGA (40 CGA) e índice de marcação por MIB-1, em uma série de tumores mamários caninos, e as possíveis correlações entre estes métodos. Foram estudados 56 tumores mamários caninos, 23 benignos e 33 malignos. Foi também avaliado o impacto prognóstico do índice mitótico (10 CGA) e o grau histológico maligno em 17 tumores malignos, sete carcinomas ductais e 10 carcinomas metaplásicos. A correlação entre os três métodos para avaliar a proliferação celular e o impacto prognóstico do índice mitótico por 10 CGA e o grau histológico maligno foi realizada. Os resultados mostraram que existe uma forte associação entre contagem de mitose e o índice de marcação por MIB-1(P<0,0001) e correlação entre contagem de mitoses em 40 CGA e índice de marcação por MIB-1 e entre índice mitótico em 10 CGA e 40 CGA (P<0,05). Observou-se correlação entre os três métodos de avaliação da proliferação celular e os fatores prognósticos semelhante aos estudos de câncer de mama humano.

Pathologic and clinical features of central neurocytoma:Analysis of 15 cases / 重庆医科大学学报

Objective:Central neurocytomas are uncommon tumors ofthe central nervous system.In order to get better recognition ofcentral neurocytoma and diminish misdiagnosis,15 cases of central neurocytoma were analyzed by retrospective study.Methods:All cases of central neurocytoma were analyzed for their clinical symptoms,pathologic changes,immunohistochemical staining,prognosis and differential diagnosis.Clinical follow-up was available for 11 patients.Results:There were 8 males and 7 females whose ages ranged from 10 to 64 years(median 32.93 years).The most common presenting symptoms were those related to increased intracranial pressure(ICP), including headache(100%),papilledema(93%)and vomiting(80%).All tumors were located in the ventricular system.The tumors were composed of uniform cells with round nuclei and a fine chromatin pattern and small cells with perinuclear halo in some areas can be seen.In particular,a fine fibrillary matrix(neuropi)lin the anuclear areas can be seen.Nuclear atypia and vascular proliferation showed in two cases,respectively.Focal necrosis could be seen in one case.Immunohistochemical findings included expression of synaptophysin (15/15),neuron specific enolase(12/15)and glial fibrillaryacidic protein(3/15).While MIB-1 proliferation indexranged from0.8% ～12.5%,and were more than 2%in 3 of 15 cases assessed.Follow-up information was available for eleven patients.Conclusion:Central neurocytomas have a favorable prognosis in general,but the clinical course of some cases could be aggressive.Increase of GFAP positivity,proliferation index and vascular proliferation might suggest a more malignant process.

A Study about Peritumoral Brain Edema in Meningiomas using Angiographic Pattern and MIB-1

OBJECTIVE: Peritumoral brain edema(PTBE) accounts for approximately 60% of meningiomas. It has not been identified why vasogenic edema, frequently shown in intra-axial tumors is also developed in extra-axial tumor such as meningiomas. Therefore, the authors assess the peritumoral brain edema of meningiomas with a focus on the angiographic pattern and expression of MIB-1 to clarify their correlation. METHODS: A total 32 cases of meningioma was studied. The authors attempted to identify 1) the location of PTBE and the edema index (EI), 2) the location and dominancy of pial supply compared with meningeal supply, 3) the biological activity of meningiomas indicated by the MIB-1 LI (labeling index), 4) their interaction. RESULTS: No PTBE was observed in the meningiomas without pial arterial supplement from internal carotid artery (ICA) and vertebral artery (VA). The PTBE of meningiomas with pial supply was developed intensely along the pial arterial supplement, and increased statistically in proportion to the extent of pial supply from ICA or VA rather than meningeal supply. Also, the MIB-1 LI in meningiomas tended to be larger in the tumors of the larger EI and the dominancy of pial supply. CONCLUSION: A strong correlation is found between the extent of PTBE in meningiomas and the dominancy of pial supply. The MIB-1 LI also tend to be associated with the PTBE. Therefore, the MIB-1 LI in benign meningiomas may represent not only the proliferative potential of the tumor, but also the biological activity like angiogenesis.

Telomerase activity and Expression of MIB-1, Fas and Fas Ligand in Placentas from Women with and without Intrauterine Growth Retardation

BACKGROUND: The placenta from a pregnancy that is complicated by intrauterine growth retardation (IUGR) tends to be smaller than that from a normal pregnancy. To investigate this difference, we analyzed the telomerase activity, the proliferative activity and the mRNA levels of apoptosis mediators in placentas. METHODS: In 20 placentas from normal third-trimester pregnancies and 22 placentas form pregnancies that were complicated by IUGR, the telomerase activity was detected by a telomeric repeat amplification protocol assay. The proliferative activity was assessed by immunohistochemical staining using the MIB-1 monoclonal antibody. The expression of the apoptosis mediator was evaluated by semi-quantitative reverse transcription-polymerase chain reactions for fas and fas ligand. RESULTS: Telomerase activity was detected in 2 (10%) of 20 normal placentas, whereas it was not observed in all tested 13 placentas that were associated with IUGR. The proliferative activity was significantly low in the placentas that were associated with IUGR (7.44+/-2.96%), compared with the normal placentas (11.0+/-3.48%, p=0.002). There was no statistically significant difference in the mRNA levels of fas or fas ligand between two groups. CONCLUSIONS: Low telomerase and proliferative activities in the placenta may play a role in the pathogenesis of IUGR.

Apoptosis in Uterine Cervical Intraepithelial Neoplasia and Cervical Carcinoma: Relationship with p53, MIB-1 and bcl-2 Expression / 대한산부인과학회잡지

OBJECTIVES: Apoptosis may play a major role in determining the growth and progression of the tumors. Certain oncogenes and tumor supressor genes are known to modulate apoptosis. The aim of study was to investigate whether apoptosis is related to the degree of differentiation, MIB-1 indicies, and expression of mutated p53 and bcl-2 in cervical neoplasms. MATERIALS AND METHODS: We examined 57 samples of normal, premalignant(i.e. mild, moderate and severe dysplasia and carcinoma in situ), malignant cervical tissue to evaluate whether differences in the apoptotic activity. Apoptotic cells and bodies were visualized by 3' end labelling. Simultaneously, quantitative immunostaining was performed for bcl-2 and p53, two known regulators of apoptosis. RESULTS: The cell proliferation index as determined by MIB-1 immunohistochemistry increased with progression from normal to cervical intraepithelial neoplasm and invasive cancer. The apoptotic index(AI) also increased with grade of lesion and was significantly associated with cell proliferation. However, the extent of apoptosis did not correlate with the expression of p53 and bcl-2. CONCLUSIONS: These results suggest that the elevation of AI in cervical neoplasm is associated with cell proliferation activity but is independent of the expression of p53 and bcl-2. It is likely that the effects on apoptosis of bcl-2 and p53 are countered by those of other oncogene products and/or additional factors that regulate apoptosis in vivo.

Expressions of MIB-1, p53 and CEA in Endocervical Glandular Lesions

BACKGROUND: Endocervical glandular lesions include glandular atypia (GA), endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS), and invasive adenocarcinoma (IA). The diagnosis of malignant glandular lesions is occasionally difficult to distinguish from benign mimickers, and the morphologic features of EGD remain unsettled. METHODS: Immunohistochemical stains for MIB-1, p53 and CEA were performed on 81 cases of paraffin-embedded endocervical glandular lesions including 22 IA, 15 AIS, 15 EGD, 13 GA, 8 microglandular hyperplasia (MGH) and 8 tubal metaplasia (TM). RESULTS: The MIB-1 labelling index of IA was 59.68%, 69.53% for AIS, 26.60% for EGD, 16.03% for benign. p53 overexpression was noted in 4 (18%) cases of IA, 3 (20%) of AIS, but none of EGD and benign lesions. It was Interesting to note that one case of MGH showed p53 staining in low intensity. Diffuse strong cytoplasmic CEA positivity was present in all of IA and AIS, whereas seven (47%) of 15 EGD and 12 (41%) of 29 benign lesions showed focal cytoplasmic CEA positivity. There were significant differences in MIB-1 and CEA immunostainings among the adenocarcinoma, EGD, and benign glandular lesions. Adenocarcinoma was closely related to p53 overexpression, although occurring in a low percentage of the cases. CONCLUSION: MIB-1 immunostaining can be useful in differentiating among endocervical adenocarcinoma, endocervical glandular dysplasia and benign glandular lesions. p53 overexpression might be helpful in the diagnosis of adenocarcinoma.

Prognostic Implications of the MIB-1 Labeling Index in Astrocytic Tumors

OBJECTIVE: The proliferative potential of intracranial glioma affects the histological malignancy and prognosis of patients with these tumors. In this study, we present the relationship between MIB-1 labeling index(LI) and clinical variables which might play the major role in determining the prognosis of patient with astrocytic tumors. PATIENTS AND METHODS:Excised tumor specimens from a total of 52 patients were stained to detect monoclonal MIB-1-Ki-67 antibody by avidin-biotin complex immunohistochemistry. The MIB-1 LI was evaluated with histological grades, demograpghic data, and survival time. The statistical significance of their correlation was analyzed by Pearson correlation test. RESULTS: The 52 patients included 30 male patients and 22 female patients. The tumors according to the criteria of the World Health Organization(WHO) classification were verified as pleomorphic xanthoastrocytoma in one, pilocytic astrocytomas 4, astrocytomas 1, anaplastic astrocytomas 3, and glioblastomas 31. MIB-1 LI in astrocytic ttumors showed no correlation with age and gender. However, the patients under 10 years had the longest survival time, whereas short survival time was observed in the older patients. The mean MIB-1 LI of different tumor grades were as follows:pleomorphic xanthoastrocytoma, 4.40+/-0.00;pilocytic astrocytoma, 4.53+/-3.09; astrocytoma, 5.50+/-6.03; anaplastic astrocytoma, 12.68+/-12.50; Glioblastoma, 21.31+/-19.63. Although the levels of MIB-1 LI were varied in individual tumors, the MIB-1 LI was increased in parallel with the histological grades. Glioblstomas showed significantly higher MIB-1 LI compared with that of anaplastic astrocytomas and low grade astrocytomas (p = 0.001). The mean survival time of entire group of patients was also well correlated with MIB-1 LI in astrocytic tumors(p = 0.015). Moreover, the mean survival time of the entire group of patients with Lis or= 10 was 60.71+/-62.58 weeks. This difference was also statistically significant(p = 0.004). CONCLUSION: The results of this study suggest that MIB-1 LI correlates with histological grades and might play a significant role in predicting the survival of patients with astrocytic tumors.

Significance on the Expression of Cyclin, MIB-1 in Benign and Malignant Papillary Lesion of the Breast / 한국유방암학회지

PURPOSE: It is difficult at times to differentiate between a papillary carcinoma and benign papilloma of the breast, and papillomas can undergo malignant transformation. The authors investigated the expression of cyclin D1 and MIB-1 to assess the diagnostic value of these markers in distinguishing papillary carcinomas from papillomas of the breast, and in determining the clinical relevance of these markers as prognostic predictors. METHODS: The medical records of 38 patients treated for benign and malignant papillary lesions of the breast at Inje University Pusan Paik Hospital between January 1992 and December 1997 were reviewed. Immunohistochemical stains for cyclin D1 and MIB-1 were performed in 30 cases of papilloma and eight cases of papillary carcinoma of the breast. The authors performed a statistical analysis of the relationship between cyclin D1 and MIB-1 with respect to the size of tumors, pathologic lymph nodes, and postsurgical residual lesions, and the recurrence and survival rates. RESULTS: Breast cancer or ADH was associated with six cases (15.79%) of papillary lesions of the breast. The incidence of postsurgical residual lesions and their recurrence were 2.63% and 2.63% in all the patients with papillary lesions of the breast. The labeling index of cyclin D1 was significantly higher in the eight papillary carcinomas (36.7+/-27.0) than in the 30 papillomas (3.5+/-4.2) (P=0.001). There was a statistically significant difference betweenn the MIB-1 labeling index of the eight papillary carcinomas (4.9+/-5.9) and that of the 30 papillomas (0.4+/-1.4) (P=0.0225). The cyclin D1 and MIB-1 expressions of the single intraductal papillomas and multiple papillomas were not different. In addition, there was no statistically significant difference of cyclin D1 and MIB-1 in the eight papillary carcinomas with respect to the associated pathologies, size, positive lymph nodes, recurrence or survival. CONCLUSION: These results suggest that cyclin D1 and MIB-1 might be useful markers for distinguishing papillary carcinomas from papillomas of the breast.