• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3065-3070
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• 2014

Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is the second most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous. This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained from NB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blocks were constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMA sections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression of these markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB, one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%) tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High and moderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it was positively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI (mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relative correlation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapy was correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as a valuable marker for the prognosis of this tumor type.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3595-3600
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• 2016

Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

• Journal of Korean Neurosurgical Society
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• v.65 no.4
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• pp.499-506
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• 2022

Objective : We conducted this study with the aim of predicting the biological behavior of meningiomas, and determining the benefits of associating histological subtype and grade with the expression of proliferative markers and tumor suppressor proteins. Methods : The study included 29 patients with primary intracranial and intraspinal meningioma diagnosed in the pathology laboratory of Konya City Hospital between January 2014 and December 2020. Clinicopathological characteristics of the patients including parameters such as age and gender were obtained from the hospital records. Histopathological findings were obtained by re-evaluating the preparations stained with Hematoxylin-Eosin, which were extracted from the archive, and by evaluating new sections obtained from paraffin blocks of patients stained with Ki67, p53, and p57 immunohistochemical stains. Results : A moderate correlation was found between tumor size and Ki67 proliferation index (PI) (p=0.003, r=0.530). There was no significant difference between grade I and grade II tumors in terms of p53 (p=0.184) and p57 (p=0.487) expressions. There were higher levels of Ki67 PI in grade II tumors. The histological subtypes of the tumor had no significant difference with Ki67 PI (p=0.018), p53 (p=0.662), and p57 (p=0.368) expressions. Conclusion : In order to obtain more definitive results, there is a need for studies, which are conducted with a greater number of patients and in multiple centers, and in which a long prospective follow-up is planned. The combination of histological, surgical, and imaging markers could make a more sensitive tool for predicting recurrence, and this could also be tested in future studies.

• Journal of Korean Neurosurgical Society
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• v.65 no.4
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• pp.558-571
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• 2022

Objective : The primary objective of this study was to identify predicting factors for local control (LC) of atypical meningioma, and we validated them with comparing the predicting factors for recurrence-free survival (RFS). We also examined the rate of LC after surgical resection with or without adjuvant treatment and RFS. Methods : Clinical and radiological records of patients with atypical meningiomas diagnosed at two institutes from January 2000 to December 2018 were reviewed retrospectively. Histopathological features were also reviewed using formalin-fixed paraffin embedded samples from pathological archives. Results : Of the 99 atypical meningiomas eligible for analysis, 36 (36.4%) recurred during the follow-up period (mean, 83.3 months; range, 12-232 months). The rate of 3-year LC and 5-year LC was 80.8% and 74.7%, respectively. The mean time-to-recurrence was 49.4 months (range, 12-150). The mean RFS was 149.3 months (95% confidence interval, 128.8-169.8 months) during the mean follow-up duration of 83.3 months (range, 12-232 months). Multivariate analysis using Cox proportional-hazard regression model showed that the extent of resection (hazard ratio [HR], 4.761; p=0.013), Ki67 index (HR, 8.541; p=0.004), mitotic index (HR, 3.275; p=0.044), and tumor size (HR, 3.228; p=0.041) were independently associated with LC. These factors were also statistically associated with RFS. In terms of radiotherapy after surgical resection, the recurrence was not prevented by immediate radiotherapy because of the strong effect of proliferative index on recurrence. Conclusion : The present study suggests that the extent of resection, proliferative index (according to Ki67 expression) and mitotic index, and tumor size are associated with recurrence of atypical meningiomas. However, our results should be further validated through prospective and randomized clinical trials to overcome the inborn bias of retrospective nature of the study design.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.557-564
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• 2009

Purpose: To evaluate the relationship between F-18 FDG uptake of tumor in PET/CT scan and pathological or immunohistochemial parameters of colorectal cancer. Materials and Methods: 147 colorectal cancer patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The pathologic results such as site, size, depth of invasion (T stage), growth pattern, differentiation of primary tumor, lymph node metastasis and Dukes-Astler & Coller stage and immunohistochemical markers such as expression of EGFR, MLH1, MSH2 and Ki-67 index were reviewed. Results: 146 out of 147 PET/CT scans with colorectal cancer showed perceptible focal FDG uptake. SUVmax showed mild positive linear correlation with size of primary tumor (r=0.277, p=0.001) and Ki-67 index (r=0.226, p=0.019). No significant difference in F-18 FDG uptake was found according to site, depth of invasion (T stage), growth pattern, differentiation of primary tumor, presence of lymph node metastasis, Dukes-Astler & Coller stage and expression of EGFR. Conclusion: The degree of F-18 FDG uptake in colorectal cancer was associated with the size and the degree of Ki-67 index of primary tumor. It could be thought that FDG uptake of primary tumor has a correlation with macroscopic and microscopic tumor growth.

• Journal of Korean Neurosurgical Society
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• v.52 no.3
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• pp.250-253
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• 2012

We report a rare case of cerebellar liponeurocytoma with an unusually aggressive histopathology. A 49-year-old man presented with a four-month history of headache, vertigo, and progressive swaying gait. Magnetic resonance imaging showed a $3{\times}3.5cm$ sized relatively well-demarcated round mass lesion in the fourth ventricle, characterized by high signal intensity on T2-weighted images. Postcontrast images revealed strong enhancement of the solid portion and the cyst wall. The patient underwent suboccipital craniectomy and tumor removal. The pathologic diagnosis was cerebellar liponeurocytoma. Adjuvant radiotherapy was offered due to concerns related to the high proliferative index (Ki-67, 13.68%) of the tumor. At the last routine postoperative follow-up visit (12 months), the patient complained of no specific symptom and there was no evidence of tumor recurrence. However, longterm follow-up and the analysis of similar cases are necessary because of the low number of reports and the short follow-up of cases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.2
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• pp.101-106
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• 2006

Purpose: The purpose of this study is to evaluate the value of proliferation factors, Ki67 and PCNA, as prognostic markers predicting the survival and neck metastasis in patients with oral cancer. Methods: 101 patients with HNSCCs, were followed retrospectively for a median period of 60 months(from 16 to 82 months). All tumors were resected surgically and examined by conventional light microscopy, immunohistochemistry. The age, sex, tumor location, clinical stage(size), metastasis, proliferative activity index(assessed by proliferating cell nuclear antigen(PCNA) and Ki67 immunoreactivity) were considered as potential prognostic factors and were correlated with patient survival. Results: Ki67 staining results ranged from 5% to 80% of tumor cell nuclei, with a median of 25%. PCNA staining results ranged from 1% to 90% with a median of 50%. With a cut-off point of 25%, patients with lower Ki67 scores showed survival advantages over those with higher Ki67 scores (p=0.0089). With cut-off point of 50%, patients with lower PCNA scores showed survival advantages over those with higher PCNA scores (p=0.0104). Pathologically neck node positive patients(n=27) showed higher PCNA expression(p=0.02) than pathologically negative neck node patients(n=39). Conclusions: The lower expressions of Ki67 and PCNA were associated with favorable prognosis such as higher survival rate and lower neck node metastasis.

• Journal of Korean Neurosurgical Society
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• v.49 no.5
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• pp.292-295
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• 2011

A rare case of intraventricular meningioma that arose in the atrium of the left lateral ventricle was identified in a 51-year-old woman. Gross total removal was performed by transcortical approach. Histopathological findings showed meningothelial meningioma with a focal atypical area which had 8% of Ki-67 labeling index (LI). A large recurrence extending into the ipsilateral quadrigeminal cistern and opposite medial occipital lobe developed approximately 41 months after the first operation. The specimens obtained from the second resection showed atypical meningioma with 20% of Ki-67 LI but there were no anaplastic area. The patient underwent fractionated stereotactic radiotherapy. However, multiple local distant metastases were found in the occipital and cerebellar cortex suggesting cerebrospinal fluid dissemination apparently 24 months after the second operation. This report presents chronological progression of a rare intraventricular atypical meningioma with more aggressive transformation.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.231-240
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• 2007

It has been reported the higher incidence rate of gastric cancer in our country. Helicobacter pylori (H. pylori), that exhibited a higher infection rate among Korean people, has been known as a cofactor to cause cancer. Therefore, the aim of this study was to identify correlations among overexpressions of COX-2 (Cyclooxygenase-2) gene, p53 mutation and cell proliferation index related to H. pylori. Taking 28 cases of gastric cancer with H. pylori detection, immunohistochemical staining for COX-2, p53 and Ki-67 were performed. In the H. pylori positive group, the well differentiated type and diffuse type of gastric cancer were distributed in larger area and the expression rate of COX-2 was revealed high. The H. pylori negative group showed higher p53 expression than that of the positive group. However, the statistical correlation between H. pylori and histopathological factors was not observed. The significantly higher expression of COX-2 had were observed in both well differentiated type and the intestinal type of gastric cancer. Although there were no statistical significances, this showed a higher inclination of manifest in the early gastric cancer. p53 exhibited a higher tendency of expression in the well differentiated, moderately differentiated and the intestinal type of gastric cancers including the early gastric cancer. Ki-67 was expressed in a significantly higher fashion along with the increase of age. In addition, it was significantly expressed in well differentiated type and intestinal type of gastric cancer. Therefore, these results suggest that H. pylori, COX-2, p53, and Ki-67 influences on the new occurrence of gastric cancer and its development procedures. In the future, the more researches would be required to focus on a larger category relative to gene expressions in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.