Ki-67 labeling index as a prognostic marker in advanced stomach cancer

Sang Hyuk Seo,Kwang Hee Kim,Sang Hoon Oh,Yunseon Choi,Ki Jung Ahn,Ji Young Lee,Sang Min Lee,박지선,Woo Gyeong Kim 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.1

Purpose: Proliferation marker Ki-67 is widely used in cancer prognosis prediction. We tried to investigate the role of Ki-67 as a prognostic factor in stomach cancer after surgery in this study. Methods: We retrospectively evaluated 251 patients who underwent curative resection for gastric cancer from 2010 to 2015. In pathologic examination, Ki-67 labeling index was defined as the percentage of Ki-67 antigen positive cells. Prognostic significance of Ki-67 for gastric cancer was evaluated. Disease-free survival (DFS) was assessed as a primary end-point. Results: The median follow-up period was 28.0 months. Thirty-one patients (12.4%) showed Ki-67 labeling index (LI) lower than 25%. Sixty-eight patients (26.6%) showed recurrence during follow-up period. Recurrence was associated with Ki- 67 LI level (≤25%, P = 0.016), and lymph node metastasis status (P = 0.002). High Ki-67 LI level (>25%) was also related to p53 positivity (P < 0.001) and poorly cohesive type (P = 0.002). The 3-year DFS was 69.4%. Low Ki-67 LI level (≤25%) was related with low DFS (47.6% vs. 72.6%, P = 0.016). T stage (P < 0.001), N stage (P = 0.006), lymphovascular invasion (P = 0.010), and neuronal invasion (P = 0.001) also affected the DFS. In addition, T stage (P = 0.03) and Ki-67 LI (P = 0.035) were independent prognostic factors for DFS. In patients treated with adjuvant chemotherapy (n = 239, 93.4%), low Ki-67 (≤25%) was a poor prognostic factor for DFS (P = 0.013). Conclusion: Low Ki-67 LI predicts high rate of progression and low DFS of stomach cancer. Ki-67 LI can be a predictive marker in resected stomach cancer treated with surgery and adjuvant chemotherapy.

위 아전절제술 후 십이지장 위 역류성 위염에서 p53 및 Ki-67 단백 발현 양상

최석채 ( Suck Chei Choi ),김용성 ( Yong Sung Kim ),김기훈 ( Ki Hoon Kim ),김헌수 ( Hun Soo Kim ),윤기중 ( Ki Jung Yun ) 대한소화기기능성질환·운동학회 2007 Journal of Neurogastroenterology and Motility (JNM Vol.13 No.2

Background/Aims: Duodenogastric reflux of bile and other contents of duodenum is one of the main etiologic fators in chronic gastritis, and chronic inflammation has been recognized as a risk factor of human cancer. The aim of this study was therefore to evaluate the expression of p53 and Ki-67 protein in duodenogastric reflux gastritis. Methods: To evaluate the proliferation activity and tumor suppressor gene expression, 16 cases of duodenogastric reflux gastritis and 16 cases of control gastric tissue after subtotal gastrectomy were examined immunohistochemically using the monoclonal antibodies to Ki-67 and p53 protein. Results: The mean duration of follow-up endoscopic biopsy after subtotal gastrectomy was 607 days in duodenogastric reflux gastritis and 556 days in control groups. The mean intensity of Ki-67 in duodenogastric reflux gastritis was significantly higher than that of control tissues (3.0 vs 2.0). The mean intensity of p53 protein in duodenogastric reflux gastritis was significantly higher than that of control tissues (2.0 vs 1.0). Conclusions: The high expressions of Ki-67 and p53 protein in duodenogastric reflux gastritis may be one of the main mechanisms in the development of gastric stump carcinoma. (Kor J Neurogastroenterol Motil 2007;13:118-122)

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

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.

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.

광선각화증, 보웬병, 편평상피세포암에서 Ki-67, Cyclin A, p53, p16의 발현 양상

이효진 ( Hyo Jin Lee ),신동훈 ( Dong Hoon Shin ),최종수 ( Jong Soo Choi ),김기홍 ( Ki Hong Kim ) 대한피부과학회 2012 대한피부과학회지 Vol.50 No.4

Background: Actinic keratosis (AK) and bowen`s disease (BD) are pre-cancerous diseases, and are regarded as an early squamous cell carcinoma (SCC). AK and BD can be progressed into SCC. In this process, tumor suppressor and cell proliferative proteins may play important roles. Objective: To investigate the differences of expression patterns of the immunohistochemical (IHC) staining and useful markers for differential diagnosis in AK, BD and SCC. Methods: Biopsy had proven 17 cases of AK, 20 cases of BD and 17 cases of SCC, which were all selected. IHC staining for Ki-67 and cyclin-A, as cell proliferative markers, p53 and p16 as tumor suppressor markers, were performed. Labeling index (LI) and distribution pattern of IHC expressions were measured. Results: LI of Ki-67 in AK, BD and SCC were 30.6%, 60.2% and 54.8%, respectively. LI of cyclin-A in AK, BD and SCC were 9.2%, 24.4% and 24.1%, respectively. LI of p53 in AK, BD and SCC were 20.7%, 37.9%, and 39.9%, respectively. LI of p16 in AK, BD and SCC were 10.6%, 38.3% and 39.9%, respectively. Lower 1/3 was the most frequent distribution pattern in AK in all IHC stains, full thickness lower 2/3 were the most frequent distribution pattern in BD and SCC in all IHC stains. Conclusion: LI and distribution pattern of Ki-67, cyclin-A, and p16, as well as the distribution pattern of p53 may be useful markers to differentiate AK from BD and SCC. Higher degree and full-thickness distribution pattern IHC expressions in all stains may be helpful in the diagnosis of BD, rather than AK. (Korean J Dermatol 2012;50(4):290∼298)

Ki - 1 임파종 1 예

강민모(Min Mo Kang),김경재(Kyoung Jae Kim),이지현(Ji Hyun Lee),최석문(Seog Mun Choi),안기성(Ki Sung Ahn),황기석(Kee Suk Whang),김용진(Yong Jin Kim),박재복(Jae Bok Park) 대한내과학회 1993 대한내과학회지 Vol.45 No.4

A 60-year-old man was admitted to our hospital complaining of fever with chillness and anarexia for 12 weeks. Physical examination revealed supraclavicular lymphadenopathy and left inguinal lymphadenopathy. Abdominal CT scan showed the evidence of maked lymphadenopathy on retraperitoneal, external iliac, obturator, left inguinal, and celiac lymph nodes. A pathologic diagnosis of Ki-1(+) lymphoma was made by the biopsed supraclavicular lymph node because the node consisted of large cells with pleomorphic nuclei, scanty cytoplasm, large basophilic nucleoli, atypical vacuoli and large cells were positive for leukocyte common antigen, Ber-H2, marker, and B-cell marker.

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>

The Conjugated Double Bond of Coniferyl Aldehyde Is Essential for Heat Shock Factor 1 Mediated Cytotoprotection

Choi, Seul-Ki,Mun, Gil-Im,Choi, Eun,Kim, Seo-Young,Kwon, Youngjoo,Na, Younghwa,Lee, Yun-Sil American Society of Pharmacognosy 2017 Journal of natural products Vol.80 No.8

<P>Coniferyl aldehyde (1) is previously reported as a potent inducer of heat shock factor 1 (HSF1). Here, we further examined the active pharmacophore of 1 for activation of HSF1 using the derivatives coniferyl alcohol (2), 4-hydroxy-3-methoxyphenylpropanal (3), and 4-hydroxy-3-methoxyphenylpropanol (4). Both 1 and 2 resulted in increased survival days after a lethal radiation (IR) dose. The decrease in bone marrow (BM) cellularity and Ki67-positive BM cells by IR was also significantly restored by 1 or 2 in mice. These results suggested that the vinyl moiety of 1 and 2 is necessary for inducing HSF1, which may be useful for developing small molecules for cytoprotection of normal cells against damage by cytotoxic drugs and radiation.</P>

Gelatin 액화세균의 생장억제에 관한 연구

이기성,崔榮吉,趙賢淑 漢陽大學校 環境科學硏究所 1983 環境科學論文集 Vol.4 No.-

Gelatin 을 재료로 이용하는 식품의 폐기물에서 gelatin 을 액화시키는 능력이 특히 뛰어난 4종의 세균을 분리·동정하였으며, 배지내에 NaCI, KI·I₂, CuSO₄등의 억제제를 농도별로 처리했을때 나타나는 4균주의 생존도 및 액화능의 변화를 비교·검토하였고, 생존도에 미치는 pH의 영향도 조사하였다. 또한 MIC(Minimal Inhibitory Concentration) Test를 시행하여 항생제에 대한 4균주의 MIC도 조사하였다. 그 결과는 다음과 같다. 1. 4균주중 H strain은 Serratia liquefaciens로, Y₁strain은 Enterobacter속으로, Y₂와 Y₃strain 은 Pseudomonas 속으로 동정되었다. 2. 배지내에 억제제로 NaCl을 처리했을 경우, 7% 농도에서 생장이 100% 억제되었으며, KI·I₂처리시에는 20ppm 에서부터 생장이 억제되기 시작하여 100ppm에서는 4개의 균주 모두 100% 생장이 억제되었다. CuSO₄처리시에는 100ppm에서부터 억제효과를 나타내기 시작하여 300ppm에서는 거의 100% 억제 효과를 보였다. 생존도에 미치는 pH의 영향을 살펴본 결과, pH 5.0, 5.5, 6.0에서는 대조군과 동일한 생존도를 나타냈으나 pH 4.0, 4.5 에서는 100% 생장이 억제되었다. 분리 균주들의 액화능 비교에 있어서는 H strain 이 가장 뛰어난 액화능을 나타내었다. CuSO₄와 KI·I₂를 각각 3ppm, 10ppm의 저농도로 처리했을 경우 4균주의 액화능은 대체로 10∼20% 감소되었다. 3. 액화 능력이 가장 뛰어난 H strain 의 MIC 는 Penicillin G; 1∼5 ㎍/ml, Spectinomycin; 12.5∼25㎍/ml, Ampicillin; <0.05㎍/ml, Cefobid; <1㎍/ml, Claforan; 0.02∼0.3㎍/ml, Tetra-cycline; >10㎍/ml로 나타났다. Tetracycline을 제외한 5가지 항생제에 대하여 H strain이 Y strain들에 비해 민감한 것으로 나타났다. 그러나 Tetracycline의 경우에는 H strain이 Y strain들에 비하여 저항성을 갖는 것으로 나타났다. Four strains of gelatin-liquefying bacteria were isolated from the sewage of the food using gelatin as the material. Treated with various concentration of NaCl, KI-I₂and CuSO₄in the culture medium and with various gradient of pH, viability of the four strains was examined and compared with each other. And also, gelatin liquefying ability was investigated in the normal culture condition and in accordance with the concentration of the inhibitor. Morever, MIC(Minimal Inhibitory Concentration) test for these strains was also carried out. The results were as follows: 1. Of the four isolated strains, the H strain was identified as Serratia liquefaciens, Y₁as the genus Enterobacter, Y₂and Y₃strains as the genus Pseudomonas. 2. Treating the culture medium with NaCl as the growth inhibitor, 7% concentration of NaCl inhibited completely the viability of all the isolated strains. Adding KI-I₂solution to the medium at the level of 20ppm, viability began to decrease and the inhibitory effect was shown 100% at 100ppm. Treated with CuSO₄at the level of 10ppm, viability began to decrease, and at 300ppm growth inhibition showed almost 100%. There was no significant difference in viability according to the pH gradient at the range of 5.0-6.0. However, at pH 4.0 and 4.5, 100% inhibitory effect on the growth was shown. Considered with the ability of gelatin liquefaction, the H strain among the four strains had the most rapid and strong ability in gelatin liquefaction. (That is, about 23 times more effective in gelatin liquefaction than that of Y₁strain) 3. Considered the MIC test, the H strain was more sensitive to Penicillin G(1-5 ㎍/ml), Spectinomycin(12.5-25㎍/ml), Ampicillin(<0.05㎍/ml), Cefobid(<1㎍/ml) and Claforan (0.02-0.3㎍/ml) than to those of the strains. Compared with the other strains, the H strain was more insensitive up to the level of 10㎍/ml to the minimal inhibitory concentration of Tetracycline.

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.