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.

[P350] A case of adenoid type basal cell carcinoma on philtrum : Very rare histopathological variant

( Won Choi ),( Kyoung Geun Lee ),( Byoung Yong Koh ),( Ki Bum Myung ),( Seung Hyun Cheong ),( Hyung Jin Hahn ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.1

Basal cell carcinoma (BCC) has been described as the most common malignant skin tumor usually seen in head and neck region. It has various histological variants and constitues about 65% of epithelial tumors. Known variants of BCC include as cystic, nodular, adenoid, morpheaform and miscellaneous forms. Of these, adenoid type BCC is regarded as a low grade malignancy compared to other types. A recent study reported the adenoid BCC incidence of 1.3%. Adenoid type of BCC has no site predilection and have been reported at various sites including forehead, inner canthus of eye, chin, trunk and extremities. A 78-year-old woman presented with a slow growing, pigmented, 0.8cm sized nodule located on the philtrum for seven years, along with an ulcerative hemorrhagic erosion lesion and rolled up edges. Skin biopsy specimens were taken by punch biopsy. Multiple cyst-like structures with strands of basaloid cells presenting with lacelike pattern, and mucoid-patterned stroma were seen. On immunohistochemical staining, SMA, CK19, C-kit were found negative while CD 10, CK5/6, p63 and p53 were positive. Also, Ki-67 was 70 %. After 18 days, excisional biopsy with skin-fat composite graft was taken from philtrum and left side of cheek. Thereafter, patient was diagnosed with adenoid BCC based on histological finding and was treated with wide biopsy with skin-fat composite graft for cosmetic aspect. Herein we report a rare case of adenoid BCC.

[P349] A case of squamous cell carcinoma arising from epidermal cyst on buttock

( Won Choi ),( Kyoung Geun Lee ),( Byoung Yong Koh ),( Ki Bum Myung ),( Seung Hyun Cheong ),( Hyung Jin Hahn ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.1

Epidermal cysts are common benign tumor of the skin. They are slow growing, round, firm intradermal or subcutaneous tumor and occur most commonly on the trunk, face and scalp. Interestingly, when an epidermal cyst ruptures and its contents are released into the dermis, foreign body reaction occurs. As a result, multinucleated giant cells may form a keratin granuloma and lead to a pseudocarcinomatous hyperplasia, which is thought to be a stimulant of squamous cell carcinoma (SCC) formation. From a review of the literature, malignant transformation of epidermal cysts is very rare and its incidence rate is known to be 0.011 -0.045%. An 82-year-old woman presented with painful, 2cm-sized subcutaneous nodule on left buttock for two years. Excisional biopsy specimens were taken from the skin lesion on buttock. In microscopic view, numerous keratinous materials were released from ruptured cysts. The specimen was consisted of well-differentiated squamous cells with atypical nucleus and mitotic figures. In mid dermis, horn pearl and the numerous multinucleated giant cells were also seen. On immunohistochemical staining, CK5/6 were positive. Also, Ki-67 and p53 were largely confined to basal portion of epithelium. The patient was diagnosed with a rare case of SCC arising from epidermal cyst based on histological finding and was later treated with complete excisional biopsy. Herein we report a rare case of SCC arising from epidermal cyst.

Clinicopathological and molecular analysis of multinodular and vacuolating neuronal tumors of the cerebrum

Choi, Euno,Kim, Seonk-Ik,Won, Jae-Kyung,Chung, Chun Kee,Kim, Seung Ki,Choi, Seung-Hong,Choi, Seongmin,Han, Bome,Ahn, Bokyung,Im, Sun-Wha,Park, Sung-Hye Elsevier 2019 Human pathology Vol.86 No.-

<P><B>Summary</B></P> <P>Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a recently recognized rare neuronal tumor, and its pathogenesis is unclear. We analyzed 7 cases of histologically typical MVNT: 6 were adults (mean age, 43.0 years [range, 23-56 years]) and 1 was a child (age, 10 years). The most common symptoms were seizures (n = 4) and headache (n = 2). The tumors were supratentorial (temporal, 5; frontal lobes, 2) in origin as reported. Vacuolated tumor cells were robustly positive for α-INA and Olig2 and at least partly positive for synaptophysin and MAP2, but negative for Neu-N, nestin and CD34. GFAP and vimentin were expressed in reactive astrocytes but not in tumor cells. Negative results were obtained for p53, IDH-1, BRAF<SUP>V600E</SUP>, H3 K27M, EGFR, Lin28A, and L1CAM. ATRX, BRG1, INI-1, and TMHH were retained. The Ki-67 labeling index was very low (<1%), and pHH3 revealed no mitotic figure. Ultrastructural features of tumor cells were comparable with those of immature neuronal cells, with several intracytoplasmic myelin-like autophagosomes and pericellular vacuolization. No <I>IDH1</I>/<I>IDH2</I> and <I>BRAF</I> <SUP> <I>V600E</I> </SUP> mutations were found upon direct sequencing. Whole-exome sequencing revealed <I>FGFR2</I>-<I>ZMYND11</I> gene fusion in 1 case. After gross total resection, all patients were alive without seizures. There was no tumor recurrence during an average period of 68 months (range, 23-101 months). The analysis of 7 typical cases of MVNT suggested that these lesions may be clonal tumors because <I>FGFR2</I>-<I>ZMYND11</I> fusion was found (1 case).</P> <P><B>Highlights</B></P> <P> <UL> <LI> “MVNT” of the cerebrum is a recently recognized rare epileptogenic neuronal tumor. </LI> <LI> Whole-exome sequencing revealed <I>FGFR2</I>-<I>ZMYND11</I> gene fusion in one of our MVNT cases. </LI> <LI> The tumor cell is robustly positive for α-INA and Olig2, but negative for Neu-N. </LI> <LI> Ultrastructurally, tumor cells have autophagolysosomes with pericellular vacuolization. </LI> <LI> There was no tumor recurrence during an average period of 68 months. </LI> </UL> </P>

Cell proliferation and neuroblast differentiation in the rat dentate gyrus after intrathecal treatment with adipose-derived mesenchymal stem cells.

Choi, Jung Hoon,Chung, Jin Young,Yoo, Dae Young,Hwang, In Koo,Yoo, Ki-Yeon,Lee, Choong Hyun,Yan, Bing Chun,Ahn, Jin Ok,Youn, Hwa Young,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2011 Cellular and molecular neurobiology Vol.31 No.8

<P>Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin (DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma. However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain.</P>

Focal adhesion kinase and src expression in premalignant and malignant skin lesions

( Ju Yeon Choi ),( Jae Yun Lim ),( Han Saem Kim ),( Jung Min ),( Jung In Kim ),( Hyun Min Seo ),( Sang Hyeon Hwang ),( Chong Won Choi ),( Yoon Hwan Kim ),( Jin Hee Sohn ),( Hyunjoo Lee ),( Won Serk Ki 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Focal adhesion kinase (FAK) and Src are non-receptor tyrosine kinases. FAK and Src play a critical role in inducing malignant transformation in tumor cells. Objectives: We performed immunohistochemical staining for total and phosphorylated forms of FAK and Src, to evaluate the role of FAK and Src in the development of premalignant and malignant skin lesions. Methods: A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen``s diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Methods: A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen``s diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Results: Cells positive for t-Src, p-Src-y530, t-FAK and pFAK-s722 were detected in premalignant intra-epithelial lesions (PELs) and squamous cell carcinomas (SCCs), but not in the perilesional skin. There was a tendency towards high correlation between Ki-67 and t-FAK or pFAK-s722, suggestive of the active role of FAK in cell proliferation. Conclusion: Our findings of higher t-Src and p-Src-y530 positive cells in PELs, as compared to SCCs (with higher Ki-67 level), are suggestive of the other role of Src in tumor formation and progression, which requires further investigation.

Effects of Streptozotocin-Induced Type 1 Diabetes on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus : Correlation with Memory Impairment

Jung Hoon Choi,In Koo Hwang,Sun Shin Yi,Ki-Yeon Yoo,Choong Hyun Lee,Hyung-Cheul Shin,Yeo Sung Yoon,Moo-Ho Won 대한해부학회 2009 Anatomy & Cell Biology Vol.42 No.1

We examined the effects of steptozotocin (STZ)-induced type 1 diabetes on cell proliferation and neuroblasts in the subgranular zone of the hippocampal dentate gyrus (SZDG) of male Wistar rats. Change in memory function was also investigated using the passive avoidance test. In the SZDG, Ki67 (a marker for cell proliferation) positive nuclei were significantly decreased at 2 and 3 weeks and slightly decreased at 4 weeks after STZ treatment. Doublecortin (DCX, a marker for neuronal differentiation)-immunoreactive (+) neuroblasts with tertiary dendrites were significantly decreased in the STZ-treated group compared to those in the vehicle-treated group. However, DCX+ neuroblasts without tertiary dendrites were abundant at 4 weeks after STZ treatment. In addition, retention latency time in STZ-treated group was similar to that of vehicle-treated group at 2 and 3 weeks after STZ treatment. However, the retention latency time was significantly decreased at 4 weeks after STZ treatment. These results suggest that STZ significantly reduced cell proliferation and neuroblasts at 2~3 weeks after STZ treatment, but not at 4 weeks after STZ treatment although memory impairment was detected at 4 weeks after STZ treatment. The gradual reduction of DCX+ neuroblasts with tertiary dendrites may be associated with the impairment of hippocampus-related memory function.

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>

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.

Effects of High Cholesterol Diet on Newly Generated Cells in the Dentate Gyrus of C57BL/6N and C3H/HeN Mice

KIM, Il Yong,HWANG, In Koo,CHOI, Ji Won,YOO, Ki-Yeon,KIM, Yo Na,YI, Sun Shin,WON, Moo-Ho,LEE, In Se,YOON, Yeo Sung,SEONG, Je Kyung Japanese Society of Veterinary Science 2009 The Journal of veterinary medical science Vol.71 No.6

<P>In this study, we observed and compared the effects of a high cholesterol diet (HCD) on cell proliferation and differentiation in the subgranular zone of the dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant strain) mice. Ki67 (a marker for cell proliferation) positive cells) were significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H mice. These results suggest that B6 strains are sensitive to HCD, which impairs cell proliferation and differentiation.</P>