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.

소화불량(消化不良)과 과심상(過心傷)의 상관성(相關性)에 대(對)한 고찰(考察) -스트레스, 기울(氣鬱), 비병증(脾病證)의 평가(評價)를 통(通)해-

김진성,윤상협,류봉하,류기원,이상욱,Kim, Jin-Sung,Yoon, Sang-Hyub,Ryu, Bong-Ha,Ryu, Ki-Won,Lee, Sang-Wook 대한한방내과학회 2004 大韓韓方內科學會誌 Vol.25 No.4

Background & Object : Dyspepsia for which no organic causes are disclosed is referred to as functional dyspepsia. Functional dyspepsia is here studied in connection with a biopsychosocial model. From the aspect of individual response to external environment, in connection with stress response, functional dyspepsia is studied by both the psychology department and the internal medicine departments. The disease is taken as approachable from the aspect of internal injury due to seven emotions and stress as differentiated by Oriental medicine. Materials and Methods : Targeted at 223 patients underwent medical checks and endoscopy at Kangnam Korean Hospital, Kyunghee University. They agreed to join this clinical experiment. Stress response inventory, GARS (global assessment of recent stress scale), GSRS (gastrointestinal symptom rating scale), diagnostic scores for Ki-depression, and Spleen Disease Differentiation of Syndromes were all measured and evaluated. The test group was comprised of functional dyspepsia patients. The control group was comprised of nonsymptomatic chronic gastritis patients who were found to suffer from chronical gastritis in endoscopy and thus could be diagnosed with functional dyspepsia if symptoms would arise, but did not complain of subjective symptoms. Results showed these corelations: Functional dyspepsia patients were found to have more serious Ki-depression compared to nonsymptomatic chronic gastritis patients. The more serious Ki-depression the more serious the dyspepsia symptoms. The higher the stress response inventory the more serious the dyspepsia. Deficiency of spleen Eum, and Deficiency and Sinking of spleen Gi were found to coincide with serious Ki-depression.

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

목적 : 십이지장 위 역류성 위염은 위절제 등에 의해서 발생하는 것으로 후에 암종이 발생할 가능성이 높은 것으로 알려져 왔다. 그러나 사람에서 십이지장 내용물의 역류와 암종 발생 사이의 병인론적 연구가 흔하지 않다. 이에 십이지장 위 역류성 위염을 보이는 환자의 조직과 대조군 환자의 조직을 대상으로 Ki-67 및 p53 단백 발현 정도를 측정하여 상피 세포증식 유도 및 암억제 유전자의 발현 정도를 비교 연구하였다. 대상 및 방법 : 위암종으로 위아전절제술을 받은 총 57예 중 내시경 및 조직학적으로 십이지장 위 역류성 위염으로 진단된 16예의 내시경 조직과 대조군 16예의 내시경 조직을 대상으로 하여 Ki-67 및 p53 단백 발현을 면역조직화학적 염색을 하였고 그 강도를 점수화하였다. 결과 : 십이지장 위 역류성 위염 소견을 보인 환자의 내시경적 추적 기간은 평균 607일, 대조군 556일 그리고 57예의 평균은 471일로 유의한 차이는 없었다. 십이지장 위 역류성 위염 환자의 Ki-67 발현 강도의 중간값은 3.0로 대조군 중간값 2.0보다 의미있게 높았으며, p53 단백의 발현 강도 중간값도 2.0으로 대조군 중간값 1.0 보다 의미있게 높았다. 결론 : 십이지장 위 역류성 위염은 담즙 등이 점막의 상피세포 증식을 유도하고 유전자 이상을 초래할 가능성이 높아 시간 경과 후 암종이 발생할 가능성이 대조군에 비해서 높을 수 있음을 알 수 있었다. 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)

Large cell acanthoma의 임상 및 병리 조직학적 소견과 Ki-67 발현 양상

정해홍(Hae Hong Jeong),서기석(Ki Seuk Suh),김상태(Sang Tae Kim) 대한피부과학회 1999 대한피부과학회지 Vol.37 No.9

N/A Background : 1970, Pinkus described large cell acanthoma(LCA) as a benign epidermal neoplasm which clinically resembles a actinic keratosis or seborrheic keratosis. However, the entity of this disease is still unclear. Objective : The purpose of this study was to find out if LCA is a distinctive entity by investigating its clinical features, histopathologic features and Ki-67 expreesion. Methods : 20 LCA samples including normal tissue were analyzed after investigating their clinicopathologic features and immunohistochemical analysis of Ki-67 expression which was performed on the formalin-fixed, praffin-embedded tissue section. The assessment of immunohistochemical staining was based on the growth fraction(GF), defined as the number of Ki-67 positive cells divided by the total number of tumor cells counted, and was expressed in a percentage. Results : 1. LCA was usually presented as a well demarcated, brown or light brown, 5 to 30 mm, round, flat to hyperkeratotic scaly patch and plaque. It predominantly affected female(5.6 female : 1 males) againg from 37 to 76 years of age(mean 51 year0old). The duration of LCA ranged from 6 months to 30 years. In eleven cases, the lesion was located on the face and in nine cases, on the extremities. Eight cases showed a solitary lesion and twelve cases showed multiple lesions. Transformation to malignancy was not found. 2. Histopathologic study showed sharply circumscribed epidemal neoplasms characterized by large(approximately twice the normal size) uniform keratinocytes with proportinally large nuclei and an increase of melanin in the basal layer. In many cases, hypergranulosis(18 cases) and hyperkeratosis(17 cases) were observed. Occasionally, acanthosis(10 cases), papillomatosis(9 cases) and epidermal atrophy(7 cases) were also observed. However, keratinocyte necrosis was not observed. Moderate solar elastosis and moderate lymphocytic infiltration was observed in the upper part of the dermis in all cases. Mild and moderate melanin incontinence was observed in 14 cases and 1 case respectively. Appendage involvement(follicular infundibulum and acrosyringium) was observed in all cases. 3. The Ki-67 expression of LCA tissue(4.87±3.10%) was significantly higher than the adjacent Ki-67 strongly suggests that LCA is a distinctive entity. (Korean J Dermatol 1999;37(9) : 1261∼1268)

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.

식도의 원주상피 피복 점막에서 점액유전자 발현 및 세포증식능에 대한 연구

최석채 ( Suck Chei Choi ),김용성 ( Yong Sung Kim ),김기훈 ( Ki Hoon Kim ),김헌수 ( Hun Soo Kim ),조향정 ( Hyang Jeong Jo ),윤기중 ( Ki Jung Yun ) 대한소화기기능성질환·운동학회 2007 Journal of Neurogastroenterology and Motility (JNM Vol.13 No.1

목적 : 바렛식도는 지속적인 위식도역류 등으로 원위부 식도에 정상적으로 존재하는 편평상피세포 대신에 배상세포를 포함하는 장형 원주세포로 식도 점막이 피복되는 것을 말한다. 그리고 이형성을 거쳐 선암종으로 진행할 수 있기 때문에 이형성 이전 단계인 바렛식도의 발암과정에 대한 연구가 필요하다. 이에 바렛식도와 배상세포를 포함하지 않은 원주세포만 있는 식도를 대조군으로 하여 점액유전자 및 세포증식능에 대해 비교 연구하였다. 대상 및 방법 : 임상 및 내시경적으로 바렛식도가 의심되어 원위부 식도에서 생검한 환자들 중에서 배상세포가 있어 조직학적으로 바렛식도로 증명된 25명의 환자와 배상세포가 없었던 환자들 중에서 무작위로 선택한 30예를 대조군으로 하였다. 생검 당시의 나이와 성별 그리고 MUC1, MUC2, Ki-67에 대한 면역조직화학적 염색을 시행하였다. 결과 : 바렛식도의 평균 나이 및 남자 비율은 각각 65.3±10.1세, 76.0%이였고, 대조군의 평균 나이 및 남자 비율은 각각 53.0±14.8세, 60.0%로 바렛식도의 나이가 대조군식도보다 의의있게 높았다. MUC1은 바렛식도 및 대조군 모두에서 100% 발현되었고, MUC2 발현율은 바렛식도 및 대조군에서 각각 92%, 20%이었다. Ki-67 발현율은 바렛식도 및 대조군에서 각각 80.0%, 70.0%이였고, Ki-67 발현 강도의 평균은 바렛식도 1.20±0.76, 대조군 0.77±0.57로 발현 강도에서 바렛식도가 의의있게 높았다. 결론 : 바렛식도는 원주세포만 있는 식도에서 보다 좀더 지속적인 위식도역류 등의 자극으로 생긴다. 그리고 MUC2는 주로 바렛식도에서 발현되고 세포증식능은 바렛식도에서 좀더 높으며 이는 MUC2 발현과 관련될 수 있다고 생각된다. Background/Aims: Barrett`s esophagus is characterized by the presence of metaplastic columnar epithelium with goblet cells in the distal esophagus. Barrett`s esophagus progresses through low grade dysplasia and high grade dysplasia to adenocarcinoma. We studied the patient age, the mucin gene and the proliferation activity of biopsy-proven Barrett`s esophagus and simple columnar epithelium-lined esophagus. Methods: To evaluate the mucin gene expression and proliferation activity, twenty five cases of Barrett`s esophagus and thirty cases of control esophagus were examined immunohistochemically with using the monoclonal antibodies to MUC1, MUC2 and Ki-67. Results: The Barrett`s esophagus patients were older (mean: 65.3±10.1 years) than the control patients (mean: 53.0±14.8 years). The MUC1 expression was 100% in both Barrett`s esophagus and the control esophagus. An MUC2 expression was observed in 92.0% of the Barrett`s esophagus and 20.0% of the control esophagus. The rate and intensity of the Ki-67 expression was higher in the Barrett`s esophagus (80.0%, 1.20±0.76) than that in the control esophagus (70.0%, 0.77±0.57). Conclusions: Barrett`s esophagus is a metaplastic lesion due to the more long-standing gastroesophageal reflux than that in a simple columnar epithelium-lined esophagus. The cause of increased proliferation activity in Barrett`s esophagus may be related to the MUC2 expression. (Kor J Neurogastroenterol Motil 2007;13:21-25)

인체 대장암 및 자궁경부암에서 PCR-SSCP법을 이용한 Ki-ras 암유전자의 점돌연변이에 관한 연구

박영홍,백낙환,김현찬,김상효,홍관희,김기태,이기영 인제대학교 1994 仁濟醫學 Vol.15 No.2

인체 대장암 20례와 자궁경부암 10례의 암조직을 대상으로 c-Ki-ras 유전자 codon 12와 13에서의 점돌연변이를 알아보고자 polymerase chain reaction(PCR)과 single-strand conformation polymorphism(SSCP) 검사법을 시행하였다. 대장암의 경우 20례중 9례(45%)에서, 자궁경부암의 경우 10례중 1례(10%)에서 양성으로 나왔다. 대장암에서는 codon 12에서 GGT가 TGT로의 치환이 4례로서 가장 많았으며, AGT, CGT로의 치환이 각 1례였고 codon 13에서는 GGC가 GAC로의 치환이 2례, TGC로의 치환이 1례인 것으로 나타났다. 자궁경부암의 경우 codon 12에서 GGT가 AGT로의 치환이 1례인 것으로 나타났다. In an attempt to clarify the role of genetic alteration in the genesis of human colorectal and cervical cancers, tissue specimens from 20 patients with colorectal cancer and 10 patients with cervical cancer were examined for the presence of point mutation in K-ras2 exon 1 by single strand conformation polymorphism analysis of PCR product. Exon I of c-Ki-ras2 was amplified by polymerase chain reaction(PCR) and comparison was made between the normal and mutated genes by nondenaturing polyacrylamide gel electrophoresis(PAGE) of PCR product and nucleotide sequence analysis using asymmetric PCR with direct sequencing. Genomic DNA from white blood cells were used as normal control and those from A427 cell line were used as mutated control. 1.PCR product from A427 cell line showed a distinct migration shift pattern compared to the normal control in PAGE and the direct sequencing indicated that nucleotide sequence of codon 12 was mutated from GGT to GAT. In addition, there was a loss of normal allele in A427 cell line. 2.PCR product from 9 cases(45%) out of a 20 colon cancer patients showed migration shifts in PAGE, and all of these 9 patients invariably demonstrated mutation of ras gene, either in codon 12(6 cases:30%) or 13(3 cases:15%). The base substitutions in codon 12 were: from GGT to AGT(1), CGT(1), or TGT(4). Base changes in codon 13 were from GGC to TGC(1) or GAC(2). 3.PCR product from 1 cases(10%) out of a 10 cervical cancer patients showed migration shrifts in PAGE, Invariably demonstrated mutation of ras gene in codon 12. The base substitutions was from GGT to AGT(1) TQE incidence of point mutation of c-Ki-ras in colon cancer was high, however, it was low in cervical cancer, which showed the relation of ruts gene mutation with colon cancer. PCR -SSCP analysis is a simple, rapid and efficient method of detection of point mutation, especially when dealing with multiple samples.

Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

Jung, So-Youn,Han, Wonshik,Lee, Jong Won,Ko, Eunyoung,Kim, Eunkyu,Yu, Jong-Han,Moon, Hyeong-Gon,Park, In Ae,Oh, Do-Youn,Im, Seock-Ah,Kim, Tae-You,Hwang, Ki-Tae,Kim, Sung-Won,Noh, Dong-Young Springer - Society of Surgical Oncology 2009 Annals of Surgical Oncology Vol.16 No.5

영어의 Yes/No의문문에 대한 한국학생들의 응답연구

성기완 우송대학교 부설 산업연구원 1999 산업연구 Vol.1 No.2

This study investigate some patterns and characteristics of reactions of Korean speakers of English to positive and negative yes/no questions and tag questions. It is observed that most Asian students manifest some difficulty in understanding the difference between structural aspects of language and semantic meaning of yes/no questions (e.g., Celce-Murcia &Larsen-freeman, 1983). Given that yes/no questions are one of the basic and yet important ways to seek and share information during communication, more in-depth research on second language learners' diverse responses to yes/no questions is much needed in the context of more real and concrete communicative settings. Accordingly, this study employed a methode of discourse analysis based on 6 taped dyadic conversations between native speakers of English and Korean speakers of English to classify and analyze reaction types of Korean speakers of English to yes/no questions. The results of the study showed that those whose levels of proficiency in English were relatively low seemed not to understand semantic structure of utterances and the specific context of communication. That is, they appeared to have difficulty in responding to both negative yes/no and tag questions. Based on the study, pedagogical suggestions of teaching various responding strategies to yes/no questions in the context of meaningful communication to help Korean nonnative speakers were also made.

RC로 구속된 조적조 벽체의 전단강도에 관한 실험적 연구

성기태,김경태 忠州大學校 2005 한국교통대학교 논문집 Vol.40 No.2

In order to investigate the effect of the height of application point of lateral loads and reinforcing steel bars in walls and columns in improving the seismic behavior of confined concrete block masonry walls, an experimental research program is conducted. A total of four one-half scale specimens are tested under repeated lateral loads. Specimens are tested to failure with increasing maximum lateral drifts while a vertical axial load was applied and maintained constant.The constant vertical axial stresses applied are 0, 0.84 and 1.80MPa, while the amount of reinforcements in horizontal and vertical directions are 0%, 0.08% and 0.18% respectively. Test results obtained for each specimen include cracking patterns, load-deflection data, and strains in reinforcement and walls in critical locations. Analysis of test data showed that above parameters generate a considerable effect on the seismic performance of confined concrete block masonry walls.