Comparison of Proliferative Activity in Each Histological Subtypes of Benign and Atypical Intracranial Meningiomas by PCNA and Ki-67 Immunolabeling

최승진,장은덕,권성오,계대곤,박춘근,이상원,강준기,Choi, Seung Jin,Chang, Eun Deok,Kwon, Seung Oh,Kye, Dae Kon,Park, Choon Keun,Lee, Sang Won,Kang, Joon Ki The Korean Neurosurgical Society 2000 Journal of Korean neurosurgical society Vol.29 No.9

목 적 : 양성 뇌수막종에 비하여 이형성 및 악성 뇌수막종이 나쁜 임상적인 예후 및 양상을 보이는 것은 잘 알려져 있으나, 양성 뇌수막종에 있어서 각각의 병리조직학적 아형에 따른 생물학적 양상의 차이에 대해서는 잘 알려지지 않거나 일부 논란이 되고있다. 본 연구에서는 이형성 뇌수막종 및 양성 뇌수막종의 각각의 병리조직학적 아형에 따른 증식능의 차이여부를 알아보고자 PCNA와 Ki-67표지지수를 분석하였다. 방 법 : 본원에서 뇌수막종으로 수술을 시행하여 얻은, 재발을 보여 재수술을 시행한 2례를 포함하여, 파라핀에 포매시킨 27개의 조직을 대상으로 병리학적인 증식능을 분석하기 위해, PCNA에 대한 단일항체 및 MIB-1 단일항체를 이용한 면역조직화학적 염색을 시행하였다. 조직학적 분류상 meningothelial type이 8례, transitional type이 9례, fibroblastic type이 5례였으며, 이형성 수막종이 5례였다. 결 과 : PCNA표지지수의 평균값은 양성 수막종에서 meningothelial type이 $4.82{\pm}5.10%$, transitional type이 $9.01{\pm}4.25%$, fibroblastic type이 $5.66{\pm}5.32%$를 보였으나 이형성 수막종에서는 $27.62{\pm}19.67%$의 높은 지수를 나타냈고, Ki-67 표지지수의 평균값은 양성 수막종의 아형에서 각각 $0.43{\pm}0.85%$, $0.44{\pm}1.08%$, $0.24{\pm}0.18%$를 보이고, 역시 이형성 수막종에서는 $0.84{\pm}0.59%$의 높은 지수를 보였다. 즉, 양성 수막종에서 각각의 아형에 따른 PCNA 및 Ki-67 표지지수는 통계학적으로 의미있는 차이는 없었으나(p>0.05), 이형성 수막종에서는 의미있는 높은 표지지수를 보여(p<0.05) 양성 수막종에서 보다 높은 증식능을 보임을 알 수 있었다. 결 론 : PCNA 및 Ki-67 표지지수를 이용한 증식능의 비교결과, 양성 뇌수막종에서는 각각의 아형에 따른 생물학적 양상이나 예후는 차이가 없을것으로 생각되나, 이형성 수막종에서는 높은 증식능을 보여 이에 대한 예후를 예상할 수 있을것으로 생각되며, 또한 이러한 표지지수가 병리조직학적으로 양성과 이형성의 감별에 많은 도움이 될것으로 사료된다. Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

담낭암의 발생에서 담췌관합류이상의 역할 규명과 암화과정에 관한 연구

한기준,송시영,정재복,이세준,김호근,강진경 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.32 No.4

The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Kim, Seung Tae,Lee, Su Jin,Lee, Jeeyun,Park, Joon Oh,Park, Young Suk,Lim, Ho Yeong,Kang, Won Ki Grune & Stratton 2017 Journal of clinical oncology Vol.35 No._suppl15

<P> e15686 </P><P> Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs. </P>

Reversal cell proliferation by exercise in the hippocampal dentate gyrus of offspring born from the stress-exposed maternal rats during pregnancy

Joon-Ki Park,Sam-jun Lee 한국스포츠학회 2015 한국스포츠학회지 Vol.13 No.4

임신중 소음스트레스를 받은 어미 쥐로부터 태어난 새끼 쥐의 뇌의 해마 치상회에서 세포분화의 표식인자인 Ki-67 과 세포분화 촉진요소인 NPY의 발현에 운동이 미치는 영향을 연구하기 위한 목적으로 교미중의 어미 쥐에서 스트레스에 노출시켜 태어난 새끼 쥐를 4집단으로 (통제군, 운동군, 스트레스군, 스트레스 및 운동군)으로 분류하여 각각 집단별 10마리로 분류를 하여 트레드밀 운동을 1주간 실시를 하였다. 운동은 태어난지 3주에서 일주일동안 시키고 희생을 시켰다. 분석은 면역조직화학법을 이용하여 분석을 하였으며, 운동은 1회 30분, 일주일로써 최초 5m/min으로 5분, 다음 8m/min으로 5분 이후 마지막으로 10m/mim으로 20분 동안 경사 없이 중정도의 강도로 실시를 하였다. 통계적인 분석은 일원변량분석을 실시하였으며, 유의수준은 .05로 설정하였다. 결과로는 통제군과 스트레스군보다 운동군과 스트레스 및 운동을 복합한 집단에서 Ki-67 및 NPY의 발현에서 유의한 차이를 보였다. 이러한 유의한 차이가 의미하는 것은 운동이 스트레스를 받고 태어난 새끼 쥐의 뇌의 세포분화의 감소를 운동을 통하여 억제시킴으로써 운동의 긍정적인 효과를 주는 것으로 볼 수가 있다.

원발성 피부 CD30 양성/ALK 음성 퇴형성 대세포 림프종 1예

이은주,김협,서영준,서기범,이증훈,박장규,김유찬,김춘옥 대한피부과학회 2003 大韓皮膚科學會誌 Vol.41 No.5

Primary cutaneous CD3O(Ki-1) Positive anaplastic large cell Iymphoma(ALCL) is a rare subset of cutaneous Iymphoma. with a much better prognosis. ALCL is a heterogeneous process that may have a T-cell, B-cell, or indeterminant(null) phenotype and which may or may not express the anaplastic Iymphoma kinase(ALK) oncoprotein. We report a case of ALCL in a 72 year old man. About 4 months ago, multiple erythematous firm ulcerative mass and satellite nodules developed on the right lower leg. The skin lesions rapidly increased in number and size. Some lesions became painful and centrally ulcered. The histologic findings showed a diffuse infiltrate of large Iymphocytes with large nuclei, prominent and multiple nucleoli, and ample cytoplasm. Immunohistochemical stainings for CD3O, CD5 were positive but stainings for LCA, CD3, CD45RO, CD2O, cytokeratin, EMA, and ALK were negative. Therefore, we diagnosed our case as CD+/30ALK- ALCL (Korean J Dermatol 2003;41(5) : 666~669)

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

Bing Chun Yan,Ki-Yeon Yoo,Joon Ha Park,Choong Hyun Lee,Jung Hoon Choi,Moo-Ho Won 대한해부학회 2011 Anatomy & Cell Biology Vol.44 No.3

Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2’-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 ㎎/㎏ EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice.

Therapeutic Effects of Recombinant Human Epidermal Growth Factor (rhEGF) in a Murine Model of Concurrent Chemo- and Radiotherapy-Induced Oral Mucositis

RYU, Seung-Hee,KANG, Ki Mun,MOON, Soo Young,CHAI, Gyu Young,HONG, Joon Pio,CHO, Kyoung-Oh,KANG, Mun-Il,CHOI, Eun Kyung,LEE, Sang-wook Journal of Radiation Research Editorial Committee 2010 JOURNAL OF RADIATION RESEARCH Vol.51 No.5

<P>Concurrent chemotherapy with radiotherapy (CCRT) has been applied for the treatment of advanced stage of head and neck cancer patients. However CCRT is associated with several complications including mucositis, dermatitis, stomatitis, etc. This study was conducted to evaluate the therapeutic effect of systemically administrated recombinant human epidermal growth factor (rhEGF) in CCRT-induced oral mucositis in a mouse model. Oral mucositis was induced in male BALB/c mice through combination treatment with cisplatin (11 mg/kg, i.p.) and irradiation (17 Gy) of the head and neck area. rhEGF (1.0 mg/kg/day for consecutive 3 days) was administered systemically, and the therapeutic effect was determined by histological evaluation of the oral mucosa. To elucidate optimal dose of rhEGF on CCRT-induced mucositis, various concentrations (0.04–3 mg/kg) of rhEGF were injected for 3 days. Systemic rhEGF administration accelerated the recovery of body weight. Histologically, rhEGF-treated mice showed significantly increased epithelial cell layer thickness, basal cell number, and expression of Ki-67 compared to control mice. Most effective dose was 1 mg/kg among other doses tested. Systemic administration of 1 mg/kg of rhEGF reduces the severity of oral mucositis induced by CCRT in a mouse model, suggesting that rhEGF can be used for treating CCRT-induced mucositis during the cancer treatment.</P>

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus.

Yan, Bing Chun,Yoo, Ki-Yeon,Park, Joon Ha,Lee, Choong Hyun,Choi, Jung Hoon,Won, Moo-Ho Korean Association of Anatomists 2011 Anatomy & Cell Biology Vol.44 No.3

<P>Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 mg/kg EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice.</P>

담낭암 발생에서 담췌관합류이상의 역할 규명과 암화과정에 관한 연구

강진경,한기준,이세준,송시영,정재복,김호근 대한소화기학회 1998 대한소화기학회지 Vol.32 No.4

Baekground/Aims: To clarify the careinogenesis of gallbladder cancer (GBC) in patients with anomalous pancreaticobiliary ductal union (APBDU), we investigated the expression of mutated p53 protein and c-erbB2, the cell proliferation indices of Ki-67 and the histopathologic changes in gallbladder carcinoma and noncaneeraus mucosa which are associated with APBDU. Methods: In the clinical review, we analysed 62 patients (27 patients of GBC with APBDU and 35 patients of GBC without APBDU) who were diagnosed in Sevrance Hospital from January, 1992 to December, 1994. Immunohistochemical staining and histologic examination were performed on the specimens obtained from surgically resected gallbladders from the patients. For comparative study, the specimens were grogped as follows: 5 cases of carcinoma with APBDU, 4 eases of noneancerous mucosa with APBDU associated with GBC, 11 cases of noncancerous mucosa with APBDU not associated with GBC, 19 cases of carcinoma without APBDU and 7 cases of chronic inflammatory mucosa of gallbladder stones as controls. Results, GBC developed in 33.3% of patients with APBDU (especially, 66.7% of PC type) and showed no gallbladder stones. The frequency of papillary carcinoma was higher and depth of invasion was less in GBC with APBDU than in GBC without APBDU. Among 15 cases of noncancerous mucosa with APBDU, isolated dysplasia and adenomyomatous hyperplasia were noted in 10 cases and 4 cases, respectively. In one case of APBDU with GBC, the expression of p53 protein was noted in the focal area of low grade dysplasia. Cell proliferation indices of Ki-67 were stepwise increased with the progression of histologic findings from inflammation, papiUary hyperplasia, metaplasia and adenomyomatous hyperplasia to dysplasia. Particularly, remarkable increase was observed in adenomyomatous hyperplasia and dysplasia. Conclusions: The high incidence of isolated dysplasia and adenomyoma accompanying with increased cell proliferative indices seems to be closely related to th carcinogenesis of GBC in patients with APBDU. Additionally, the mutation of p53 may contribute to early event of carcinogenesis in some patients with APBDU.

Systemic administration of low dosage of tetanus toxin decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

Bing Chun Yan,In Hye Kim,Joon Ha Park,Ji Hyeon Ahn,Jeong-Hwi Cho,Bai Hui Chen,Jae-Chul Lee,Jung Hoon Choi,Ki-Yeon Yoo,Choong Hyun Lee,Jun Hwi Cho,Jong-Dai Kim,Moo-Ho Won 한국실험동물학회 2013 Laboratory Animal Research Vol.29 No.3

In the present study, we investigated the effect of Tetaus toxin (TeT) on cell proliferation and neuroblast differentiation using specific markers: 5-bromo-2-deoxyuridine (BrdU) as an exogenous marker for cell proliferation, Ki-67 as an endogenous marker for cell proliferation and doublecortin (DCX) as a marker for neuroblasts in the mouse hippocampal dentate gyrus (DG) after TeT treatment. Mice were intraperitoneally administered 2.5 and 10 ng/kg TeT and sacrificed 15 days after the treatment. In both the TeT-treated groups, no neuronal death occurred in any layers of the DG using neuronal nuclei (NeuN, a neuron nuclei maker) and Fluoro-Jade B (F-J B, a high-affinity fluorescent marker for the localization of neuronal degeneration). In addition, no significant change in glial activation in both the 2.5 and 10 ng/kg TeT-treated-groups was found by GFAP (a marker for astrocytes) and Iba-1 (a marker for microglia) immunohistochemistry. However, in the 2.5 ng/kg TeT-treated-group, the mean number of BrdU, Ki-67 and DCX immunoreactive cells, respectively, were apparently decreased compared to the control group, and the mean number of each in the 10 ng/kg TeT-treated-group was much more decreased. In addition, processes of DCX-immunoreactive cells, which projected into the molecular layer, were short compared to those in the control group. In brief, our present results show that low dosage (10 ng/kg) TeT treatment apparently decreased cell proliferation and neuroblast differentiation in the mouse hippocampal DG without distinct gliosis as well as any loss of adult neurons.