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.

Human Papillomavirus 16/18 Expression of Endocervical Glandular Lesions: Relationship with p53 and MIB-1 Expressions

The pathogenesis of endocervical glandular lesions are not clearly understood. The aims of this study are to evaluate the etiologic role of human papillomavirus (HPV) 16/18 and the relationship of HPV 16/18, p53 and MIB-1 expressions in endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma. The materials included 14 endocervical adenocarcinoma and 5 AIS and 18 high grade EGD and 39 low grade EGD. Immunohistochemistry for p53 and MIB-1, and in situ PCR for HPV 16/18 were done. HPV 16/18 positivity was 84.2%, 16.7% and 17.9% in malignant glandular lesion (adenocarcinoma and AIS), high grade EGD and low grade EGD, respectively. P53 protein expression rates of malignant glandular lesions, high grade EGD and low grade EGD were 31.6%, 11.1%, and 0%, respectively. High MIB-1 labelling index was found in 73.7% of malignant glandular lesions, but in only 5.7% and 3.6% of high and low grade EGD, respectively. There were statistically significant differences in HPV 16/18, p53 and MIB-1 expressions between malignant endocervical glandular lesions and EGD, but no significant difference in p53 and MIB-1 expressions in relation to HPV 16/18 expression. In malignant endocervical glandular lesions, HPV 16/18 infection may be a major causative factor, but not be related to p53 and MIB-1 expressions.

Correlation between p53 and MIB1 Index Expression of Primary Tumor and Metastatic Lymph Node in Breast Cancer / 한국유방암학회지

PURPOSE: This study was designed to elucidate the biology of cancer metastasis and differences in the biologic status between primary tumors and metastatic lymph nodes of invasive breast cancer by comparing the well known prognostic factors p53 gene mutation, p53 protein expression and the MIB-1 index. An additional goal was to investigate the p53 mutational pattern of breast cancer patients. METHODS: We used the PCR-SSCP method to detect p53 gene mutation and immunohistochemical staining to establish p53 protein expression and the MIB-1 labelling index in 25 primary tumors and metastatic lymph nodes from breast cancer patients. We then made a comparison the between primary tumors and the metastatic lymph nodes. RESULTS: The results indicated a correlation between histologic grade and p53 gene mutation as well as p53 protein expression, but showed no correlation to MIB-1 labelling index. The concordance rates of p53 gene mutation and p53 protein expression between the primary tumors and metastatic lymph nodes were 72% and 100%, respectively.Three cases showed a different mutated exon number between the primary tumors and the metastatic lymph nodes. Some cases showed p53 gene mutation only in the primary tumors, but while other cases only in the metastatic lymph nodes. The MIB-1 labelling index increased with tumor grade. The p53 altered group show a higher mean MIB-1 index than the non altered group's in both the primary tumors and metastatic lymph nodes. CONCLUSION: p53 gene mutation is not consistent with p53 protein expression and there are some differences in p53 gene mutation between primary tumors and metastatic lymph nodes in breast cancer. Therefore, metastatic tumor have different characteristics from those of primary tumors. In breast cancer, metastasis is regulated not only by an up- regulating mechanism but also by a down-regulating mechanism.

Correlation between p53 and MIB1 Index Expression of Primary Tumor and Metastatic Lymph Node in Breast Cancer / 한국유방암학회지

PURPOSE: This study was designed to elucidate the biology of cancer metastasis and differences in the biologic status between primary tumors and metastatic lymph nodes of invasive breast cancer by comparing the well known prognostic factors p53 gene mutation, p53 protein expression and the MIB-1 index. An additional goal was to investigate the p53 mutational pattern of breast cancer patients. METHODS: We used the PCR-SSCP method to detect p53 gene mutation and immunohistochemical staining to establish p53 protein expression and the MIB-1 labelling index in 25 primary tumors and metastatic lymph nodes from breast cancer patients. We then made a comparison the between primary tumors and the metastatic lymph nodes. RESULTS: The results indicated a correlation between histologic grade and p53 gene mutation as well as p53 protein expression, but showed no correlation to MIB-1 labelling index. The concordance rates of p53 gene mutation and p53 protein expression between the primary tumors and metastatic lymph nodes were 72% and 100%, respectively.Three cases showed a different mutated exon number between the primary tumors and the metastatic lymph nodes. Some cases showed p53 gene mutation only in the primary tumors, but while other cases only in the metastatic lymph nodes. The MIB-1 labelling index increased with tumor grade. The p53 altered group show a higher mean MIB-1 index than the non altered group's in both the primary tumors and metastatic lymph nodes. CONCLUSION: p53 gene mutation is not consistent with p53 protein expression and there are some differences in p53 gene mutation between primary tumors and metastatic lymph nodes in breast cancer. Therefore, metastatic tumor have different characteristics from those of primary tumors. In breast cancer, metastasis is regulated not only by an up- regulating mechanism but also by a down-regulating mechanism.

Assessment of MIB1 (Ki-67) Labeling Index and Correlation with Other Well Established Prognostic Factors in Breast Cancer

PURPOSE: The MIB1 labeling index is new method utilizing a monoclonal antibody against Ki-67 antigen and useful for evaluating the proliferation rate in breast cancer due to its ease of use and reliability. We compared the MIB1 labeling index to other, well established prognostic factors and assessed the prognostic value of MIB1 in 564 breast cancers. METHODS: The MIB1 (Ki-67 equivalent monoclonal antibody) proliferation rate, MIB1 labeling index, was determined in formalin-fixed, paraffin-embedded tissue specimens of 564 primary breast cancer patients who underwent surgery between March 1998 and February 2000 at Seoul National University Hospital. The clinicopathologic characteristics of the primary tumor such as age, tumor size, histologic type, nuclear grade, histologic grade, hormone receptor status and various tumor markers (p53, c-erbB-2, bcl-2) were compared with the value of the MIB1 labeling Index. RESULTS: The mean value of MIB1 labeling index was 6.9. MIB1 labeling index was correlated to younger age (p= 0.011), histologic types, low nuclear grade (p=0.0001), high histologic grade (p=0.0001), p53 positive (IDC) (p=0.0001), c-erbB-2 positive (DCIS) (p=0.01), comedo type (DCIS) (p= 0.001) and inversely correlated to hormone receptor positivity (p=0.0001), bcl-2 positive (IDC) (p=0.001). No correlation was found in tumor size, lymph node status and c-erbB-2 positive (IDC). CONCLUSION: The MIB1 labeling index correlated well with well-established poor prognostic factors. The MIB1 labeling index may be an important prognostic determinant in breast cancer.