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

Diagnosis experience of sarcomatoid renal cell carcinoma / 中华泌尿外科杂志

Objective Explore the diagnosis experience of sarcomatoid renal cell carcinoma (SRCC).Method There were 5 cases of SRCC from April 2011 to June 2013,3 of them were females and 2 were males,with a mean age of 49 (27-71).All the patients were presented with pain accompanied with other symptoms such as hematuria,fever and polyuria.CT urography suggested renal occupied lesions,withuneven density and enhancement,and malignancy was highly suspected.The mean diameter of tumors was 9.2 cm(4-18 cm).Radical nephrectomy was performed on all patients,tumors were located in renal parenchymal,and with adherence to other tissues.One patient with lung metastasis was found before surgery.Result Pathologic findings of the resected tissues after operation noted SRCC.Under the microscope,a large number of spindle shaped cells were seen,and Vimentin and PCK were all positive in immunohistochemical.Three patients with metastases were found after surgery (adrenal gland,liver,pancreas).Postoperative pathological stages were one T2N0M1,three T4N0M1 and one T3N0M0.One patient received IL-2 immunotherapy.All patients died within 9 months after surgery with a median survival of 3.8 months.Immunohistochemistry in the postoperative,there were four patients with the level of Ki-67 LI ＞ 50％,with distant metastasis and survival time was 1-4 moths.Conclusion The disease develops rapidly,and the prognosis of the patients is very poor.The Ki-67 LI may be considered as a prognosis marker and the patients with sarcomatoid differentiation can benefit little from surgery alone.

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.

Peritumoral Brain Edema in Meningiomas : Correlation of Radiologic and Pathologic Features

OBJECTIVE: The primary objective of this study was to perform a retrospective evaluation of the radiological and pathological features influencing the formation of peritumoral brain edema (PTBE) in meningiomas. METHODS: The magnetic resonance imaging (MRI) and pathology data for 86 patients with meningiomas, who underwent surgery at our institution between September 2003 and March 2009, were examined. We evaluated predictive factors related to peritumoral edema including gender, tumor volume, shape of tumor margin, presence of arachnoid plane, the signal intensity (SI) of the tumor in T2-weighted image (T2WI), the WHO histological classification (GI, GII/GIII) and the Ki-67 antigen labeling index (LI). The edema-tumor volume ratio was calculated as the edema index (EI) and was used to evaluate peritumoral edema. RESULTS: Gender (p=0.809) and pathological finding (p=0.084) were not statistically significantly associated with peritumoral edema by univariate analysis. Tumor volume was not correlated with the volume of peritumoral edema. By univariate analysis, three radiological features, and one pathological finding, were associated with PTBE of statistical significance: shape of tumor margin (p=0.001), presence of arachnoid plane (p=0.001), high SI of tumor in T2WI (p=0.001), and Ki-67 antigen LI (p=0.049). These results suggest that irregular tumor margins, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI can be important predictive factors that influence the formation of peritumoral edema in meningiomas. By multivariate analysis, only SI of the tumor in T2WI was statistically significantly associated with peritumoral edema. CONCLUSION: Results of this study indicate that irregular tumor margin, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI may be important predictive factors influencing the formation of peritumoral edema in meningiomas.

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.

Correlation of Ki-67, nm23-H1 and the VEGF Expression with the Clinicopathological Variables for Distant Recurrence after Curative Surgery for Carcinoma of the Ampulla of Vater

PURPOSE: Not a few patients show early distant recurrence after curative resection for carcinoma of the ampulla of Vater, and this recurrence is not just related to the clinicopathological factors. This study was performed to determine the correlation of the clinicopathological and biological characteristics with early distant recurrence after surgery for carcinoma of the ampulla of Vater. METHODS: Of the 158 patients who underwent curative resection for carcinoma of the ampulla of Vater at the Samsung Medical Center between December 1994 and August 2004, 38 patients (the recurrence group) with distant recurrence within a year after surgery and 32 patients (the non-recurrence group) without recurrence for more than 3 years after surgery were retrospectively analyzed. Evaluation of their clinicopathological characteristics and their immunohistochemical staining for Ki-67 antigen, nm23-H1 protein and vascular endothelial growth factor (VEGF) were carried out. RESULTS: Of the recurrence group, 24 patients (63.2%) had multiple recurrence sites and 10 (26.3%) were TNM stage I after surgery. The TNM stage was significantly advanced in the recurrence group. Both the Ki-67 labeling index (LI) (10.2% vs. 5.8%, respectively) and positive rate (50.0% vs.18.8%, respectively) according to the cut-off value of Ki-67 LI (i.e. 9%) were significantly higher in the recurrence group. The immunoreactivity for nm23-H1 protein and VEGF was not different between the two groups. Only lymph node metastasis was statistically significant on the multivariate analysis for early distant recurrence after surgery. CONCLUSION: The recurrence group showed an advanced TNM stage and increased Ki-67 LI. Lymph node metastasis was the single independent poor indicator for early distant recurrence after curative resection for carcinoma of the ampulla of Vater.

Proliferative Markers of Breast Cancer / 한국유방암학회지

PURPOSE: The mitotic index (MI) and Ki-67 labeling index have been used as cell proliferative markers in the various tumors. Topoisomerase II alpha (Topo II alpha) is also expressed in proliferating cells. The aim of this study was to evaluate the correlations between the MI, Ki-67, and Topo II alpha expression as proliferative markers of breast cancer. METHODS: The cell proliferative activity of 181 breast cancers was measured using MI, Ki-67 labeling index and Topo II alpha expression. The correlation between the measured markers was also analyzed. RESULTS: The MI, Ki-67, and Topo II alpha were significantly correlated with each other(p < 0.000). The MI and Ki-67 labeling index were associated with high histological grade, and absence of hormone receptor (p < 0.000). Topo II alpha expression was correlated with high histological grade (p < 0.000), absence of hormone receptor and HER-2/neu overexpression (p < 0.043). The MI, Ki-67, and Topo II alpha were not associated with any other clinical variables, such as age, tumor size, and lymph node status. CONCLUSION: The three proliferative indices were significantly associated with aggressive features of breast cancer, and significantly correlated with each other.

Malignant Variant of the Central Neurocytoma

Central neurocytoma is a rare, well-differentiated neuronal tumor and is usually located in the lateral or third ventricle of young adults. Its overall prognosis is excellent with a low proliferative index. The majority of previously reported malignant variants rarely did recurred after tumor removal and regarded as benign tumor despite of histopathological malignant feature. Nevertheless, we experienced a case of malignant variant of the central neurocytoma with high proliferative index(Ki-67 labeling index >30%), which showed recurrence immediately after surgery and died within 3 months POD. Here, we describe the case with a review of the literatures.

Correlation of Clinical Stage and Presumptive Prognostic Factors in Renal Cell Carcinoma

Renal cell carcinoma is the most common primary cancer of the kidney. The tumor stage is a reliable prognostic marker in renal cell carcinoma which is significantly associated with patient survival. But assessment of other prognostic factors has produced varying and often conflicting results. We reevaluated the significance of varied prognostic parameters in 33 cases of renal cell carcinoma; clinical stage, cell type, histologic pattern, DNA ploidy, Ki-67 labeling index, and bcl-2 oncoprotein expression. We could not statistically prove that DNA ploidy and bcl-2 expression were related to any examined parameters. Cell type was not related to clinical stage nor nuclear grade but there was a significant correlation (p=0.002) between cell type and histologic pattern. Nuclear grade (p=0.007) and Ki-67 labeling index (p=0.036) were significantly related to clinical stage, suggesting their value as complementary prognostic markers for renal cell carcinoma.

Correlation of Clinical Stage and Presumptive Prognostic Factors in Renal Cell Carcinoma

Renal cell carcinoma is the most common primary cancer of the kidney. The tumor stage is a reliable prognostic marker in renal cell carcinoma which is significantly associated with patient survival. But assessment of other prognostic factors has produced varying and often conflicting results. We reevaluated the significance of varied prognostic parameters in 33 cases of renal cell carcinoma; clinical stage, cell type, histologic pattern, DNA ploidy, Ki-67 labeling index, and bcl-2 oncoprotein expression. We could not statistically prove that DNA ploidy and bcl-2 expression were related to any examined parameters. Cell type was not related to clinical stage nor nuclear grade but there was a significant correlation (p=0.002) between cell type and histologic pattern. Nuclear grade (p=0.007) and Ki-67 labeling index (p=0.036) were significantly related to clinical stage, suggesting their value as complementary prognostic markers for renal cell carcinoma.

Proliferative Activity of Thyroid Lesions Evaluated by Mitotic Count and Proliferating Cell Nuclear Antigen (PCNA)

To evaluate the clinical and histopathological significance of the proliferative activity in neoplastic and non-neoplastic thyroid lesions, we analyzed the mitotic count and the proliferating cell nuclear antigen labeling index (PCNA-LI) by immunohistochemistry as the proliferation- related markers. In this study included were surgically removed normal thyroid tissue (27 cases), adenomatous goiter (15 cases), Hashimoto's thyroiditis (5 cases), follicular adenoma (13 cases), follicular carcinoma (7 cases), papillary carcinoma (44 cases), poorly differentiated carcinoma (2 cases) and undifferentiated carcinoma (3 cases). The median PCNA-LI was 0 in normal thyroid tissue, 0.5 in adenomatous goiter, 6.2 in Hashimoto's thyroiditis, 1.2 in follicular adenoma, 4.8 in follicular carcinoma, 8.5 in papillary carcinoma, 60.8 in poorly differentiated carcinoma, and 55.2 in undifferentiated carcinoma (p=0.0001). Although PCNA-LI was exceptionally high in Hashimoto's thyroiditis, it was suggested that PCNA-LI could be used as a marker differentiating benign lesions from malignant neoplasm. Also, it could differentiate follicular adenoma from follicular carcinoma. Except clinical stage (p=0.0397), PCNA-LI was not related with sex, size, histologic subtype, and lymph node metastasis in papillary carcinoma. The presence of mitosis differentiated the neoplastic thyroid lesions from the non-neoplastic lesions (p<0.05), however, it could not divide benign and malignant neoplasm. These results suggest that an evaluation of the proliferative activity can help to differentiate the thyroid lesions. In addition, there was no significant correlation between the value of PCNA-LI and the presence of mitosis. It can be recommended to evaluate both the mitotic count and the PCNA-LI for determining the proliferative activity of the thyroid lesions.

Aberrant Expression of p53, MCM2 Protein and Proliferative Activity in Glioma

In gliomas, the most frequently studied tumor suppressor gene is the p53 gene which has been found to be mutated in a considerable fraction of astrocytomas and glioblastomas. Mutations that alter the function of the p53 gene product are thought to play a critical role in glial tumorigenesis. The murine double minute 2(MDM2) gene has been shown to code for a cellular protein that forms a complex with the p53 tumor suppressor gene product and inhibits its function. The fact that MDM2 can negatively regulate p53 suggests MDM2 could function as an oncogene when overexpressed. We investigated the expression of p53, MDM2 and proliferative activity of the tumor cells in 71 cases of gliomas(17 cases of differentiated astrocytomas. 25 cases of anaplastic astrocytomas and 29 cases of glioblastomas). Their paraffin-embedded tissue sections were immunostained with monoclonal antibody(p53 and PCNA, proliferating cell nuclear antigen) and polyclonal antibody(MDM2) for detection of p53, MDM2 and PCNA respectively. The results were as follows: The p53 staining was positive in 28 cases(39.4%) and MDM2 staining in 5 cases(7.0%) of 71 gliomas. The p53 positive-staining was detected in 2 cases(11.8%) of 17 differentiated astrocytomas, 9 cases(36.0%) of 25 anaplastic astrocytomas and 17 cases(58.6%) of 29 glioblastomas. The p53 expression was associated with malignancy grade(p<0.005) and proliferative activity was strongly associated with malignancy grade(p=0.0001). The p53 expression was closely associated with proliferative activity : p53-positive tumors had significantly higher median PCNA-labeling index than p53-negative tumors(40.6+/-10.1% versus 19.6+/-15.0%)(p=0.0001). But, MDM2 expression was not associated with proliferative activity(p=0.4575). The proportion of p53 immunoreactivity had significant association with proliferaive activity: the more the proportion of p53 immunoreactivity increased, the higher PCNA-labeling index elevated(p=0.0001). None of the tumors with MDM2 expression showed immunoreactivity for p53. These results suggest that the mutation of p53 gene plays a critical role in malignant transformation in glioma and it could be the prognostic factor for histologically same grade gliomas and that a subset of human gliomas escapes from p53-regulated growth control by amplification and overexpression of MDM2. Therefore gene study targeting these genes may be useful for the management of human glioma as a diagnostic modality.

Expression of brdU in BBN induced rat bladder tumor / 대한비뇨기과학회지

We labeled-S-phase cell in BBN induced rat bladder tumors using anti-bromodeoxyuridine anti- body. The thymidine analogue, bromodeoyuridine (BrdU), was incorporated into DNA during the S -phase or the cell cycle. Anti-BrdU monoclonal antibody can be detected by the immunohistochemical method for an in vivo labeling study. Sequential cellular change (normal, simple hyperplasia, nodular or papillary hyperplasia, and transitional cell carcinoma-Ta, T1) was observed in rat urinary bladder according to the duration of BBN administration. The BrdU labeling index, S phase fraction, was determined by counting the number of BrdU labeled cells in the tissue section. The average labeling index obtained using this method in normal, simple hyperplasia(SH), nodular or papillary hyperplasia(NPH), and bladder tumor (Ta. T1) was 1.7, 5.6, 11.2, and 18.9 (14.9, 21.9), respectively. Also, the higher S phase fraction was found in grade II than in grade I .The higher S phase fraction indicated greater biological malignancy based on the fact that mean labeling index progressively increased with tumorigenesis. However, mean labeling index at NPH did not significantly differ from that of Ta, which implies that NPH might represent the similar cellular characteristics.

Cell kinetics of human transitional cell carcinoma of the bladder by in vitro bromodeoxyuridine labeling / 대한비뇨기과학회지

We labeled S-phase cell in human bladder tumors using anti-bromodeoxyuridine (BrdU) antibody. The thymidine analogue, BrdU, was incorporated into DNA synthesis phase by in vitro labeling technique. Separate samples of 27 transitional cell bladder cancers were labeled, fixed with 7O per cent ethanol, embedded in paraffin, sectioned and stained by an immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index (LI), S phase fraction, was determined by counting the number of bromodeoxyuridine labeled cells in the tissue sections. The average LI in normal and bladder tumors were 2.99% and 11.8% respectively. All grade I and grade II tumors had a LI lower than 10%. while the average LI in grade III tumors was 2l.46%. The average LI for noninvasive (Ta and T1) and invasive tumors were 7.75 % and 26% respectively. The average LI in recurrent tumors were 15.37% compared to 7.76% in initial tumors. The high labeling index in tumors tissue appears to indicate a more malignant potential and thus a poor prognosis. Although further studies are required for its full significance, the measurement of BrdU labeling index by in vitro method may be a quantitative assay of biological potential of individual tumors and has practical value in the management of transitional cell carcinoma of the bladder.