Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

Haroon, Saroona,Hashmi, Atif Ali,Khurshid, Amna,Kanpurwala, Muhammad Adnan,Mujtuba, Shafaq,Malik, Babar,Faridi, Naveen Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Introduction: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO do not recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We therefore aimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymph node metastasis, ER, PR and HER2neu status. Methods: A total of 194 cases of newly diagnosed breast cancer were included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed by the DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated both as continuous and categorical variables. Results: Mean age of the patients was 51.7 years (24-90). Mean Ki67 index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%) and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade, PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size. There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen with HER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as compared to intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. Conclusion: Our study indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognostic markers because we found that tumors with Ki67 higher than 30% have better prognostic profile compared to tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis and HER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate and low groups when considering adjuvant chemotherapy and prognostic stratification.

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.

Ki-67이 Luminal B형 유방암 환자의 예후에 미치는 영향

류동원,최우식,이충한 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.1

배경: Ki-67는 세포의 분열지수로서 특히 세포분열초기 나타나는 것으로 알려져 있다. 그래서 Ki-67의 분열지수가 높은 경우 조기 재발 및 예후와 관련되어 있다는 보고가 있다. 본 연구에서는 본원의 자료를 토대로 Ki-67의 분열지수가 예후에 영향을 미치는지를 알아보고자 한다 방법: 2001년 1월부터 2005년 12월까지 본원에서 유방암으로 수술을 받은 679명의 환자를 대상으로 후향적으로 조사를 하였다. 술후 조직병리학적 보고서를 토대로 조사하였다. Ki-67의 수치를 기준으로 10%이하군, 10%에서 20%군, 20%이상군으로 나누었다. 세군사이의 임상병리학적 요소의 분포를 비교하였으며 Kaplan-Meier를 이용하여서 생존율을 분석하였다. 결과: 환자들의 평균나이는 46세였으며, 평균종양의 크기는 3.2cm였다. 20%이상군에서 진행성 유방암환자의 비율이 높았다.(p=0.007) 특히 림프절의 전이정도와도 관련이 있었다.( p=0.003) 그러나 Ki-67과 생존율과는 의미있는 관련성을 없었다.( p=0.6112). 결론: 본원의 조사에 따르면 Ki-67은 진행성 유방암과 호르몬 수용체 음성과는 밀접한 관계를 가지고 있었으나 생존율에는 영향을 미치지 않았다. 그러나 본조사는 추적기간이 짧고 조사 규모가 크지 않아서 향후 계속적으로 추적 관찰한다면 더 의미있는 결과과 나올것이다. Background: Ki-67 expression has been considered to be a reliable marker for assessing tumor cell proliferation. The aims of the ourstudy were to assess the correlationbetween Ki-67 expression and clinocopathologic factors and to analyze the effect of Ki-67 expression on survival rate. Methods:The study subjects, 679 women with breast cancer, were a subset of patients operated at OOO hospital from Jun 2001 to Dec 2005.Patients are grouped into 3 categories according to Ki-67 determined in surgical specimens. Clincopathologic factors were compared with 3 categories of Ki-67. Chi-squared tests were used for statistical analysis. Kaplan–Meier estimates are presented for thesurvival function, and differences in survival were analyzed usingthe log rank test. Results: The median age was 46yrs, and median tumor size was 3.2cm. The strong correlation was observed between tumor staging and Ki-67 staining(p=0.007) and Group III(more than 20% staing) showed more advanced N-staging(p=0.003). The number of patients with estrogen receptor negative was higher in Group III(p=0.001) and that with HER-2 receptor positive was also higher in Group III(p =0.001) comparing with other groups. The univariate analysis for prognostic factors associated with DFS revealed that both the tumor groupas T1, T2, T3 or T4 and lymph node as N0, N1, N2 or N3 were statistically significant(p=0.0003 and p=0.0015 respectively) but the Ki-67 staining as <10%, 10~20%, >20% was statistically not significant(p=0.6112). The univariate analysis for prognostic factors associated with OS revealed that Tumor staging and N-staging was statically significant(p=0.003 and p=0.0015 respectively). Conclusions: According to our study, Ki-67 positive groups was associated with more advanced staging, ER-negative, PR-negative and HER-positive respectively. But there is no significant association between Ki-67 staining and 5-year disease free survival rate including overall survival rate.

악성 상피성 난소종양에서 Ki-67의 발현에 관한 연구

박창민 ( Chang Min Park ),한송이 ( Song Yee Han ),김인선 ( In Sun Kim ),김현철 ( Hyun Chul Kim ),강재성 ( Jae Seong Kang ) 대한산부인과학회 2008 Obstetrics & Gynecology Science Vol.51 No.11

목적: 세포증식지수인 Ki-67을 면역조직화학적 염색하여 상피성 난소암종의 예후인자인 수술적 병기, 조직학적 유형, 조직학적 분화도, 치료 전 혈청 CA-125와의 관계를 분석하여 예후인자들과 연관성을 알아보고 독립적인 예후 인자로 가치여부를 구명하고자 한다. 방법: 1994년 1월부터 2005년 12월까지 고려의대 안암병원 산부인과에서 난소암종으로 개복수술한 100명의 환자에서 수술 후 얻은 난소조직을 대상으로 하여 Ki-67에 대한 MIB-1단클론 항체를 사용하여 면역조직화학 염색을 시행 후 핵에 진한 갈색으로 염색된 세포수를 종양세포수의 백분율로 표시하였다. 결과: KI-67 과발현은 총 100명 중 63예 (63.0%)이고, 병기에 따른 과발현은 병기 I 및 II기에서 각각 42.9%, 33.3%, 병기 III 및 IV에서 각각 72.4%, 66.7%로 저병기 (I, II)보다 고병기 (III, IV)에서 과발현되어 통계학적으로 유의한 차이가 있었다. 조직학적 유형에 따른 Ki-67의 과발현은 장액성 암종에서 76.3%, 점액성 암종, 자궁내막양 암종 및 투명세포암종에서 각각 53.6%, 54,5%, 58.3%로 장액성 암종에서 타 유형에서보다 발현이 많았으나 통계학적으로 유의성은 없었다. 분화도에 따른 Ki-67의 과발현은 분화도 3에서 70.9%, 분화도 1 및 2에서 각각 50.0%, 54.5%로 분화도가 나쁜 경우 Ki-67의 발현율이 높았으나 통계학적인 유의성은 없었다. 치료 전 혈청 CA-125에 따른 Ki-67의 과발현은 CA-125가 높은 경우 증가하는 경향은 있으나 통계학적인 의의는 없었다. Ki-67단백의 과발현은 난소의 상피성 암종의 생존기간에 유의한 감소가 있었다. 결론: Ki-67의 과발현은 치료예후를 예측할 수 있는 인자로 활용할 수 있다고 판단된다. Objective: The study was to evaluate the biological significance of Ki-67 expression in common epithelial ovarian carcinomas. We investigated the correlation between Ki-67 expression and clinicopathological parameters. Methods: One hundred patients with epithelial ovarian carcinomas stage I-IV treated at Department of Obstertrics and Gynecology, Korea University Hospital from January 1994 to December 2004 were used as study group. We determined expression of Ki-67 by immunohistochemistry using MIB-1 monoclonal antibody reactivity. Results: Ki-67 overexpression was higher in high stage (III-IV) than low stage (I-II) (P<0.013). Ki-67 overexpression was higher in serous cystadenocarcinoma (76.3%) than mucinous cystadenocarcinoma (53.6%), endometrioid carcinoma (54.5%) and clear cell carcinoma (58.3%) but it was not statistically significant (P<0.191). Ki-67 expression was higher in high grade but it was not statistically significant (P<0.096). Ki-67 overexpression was not correlated with serum CA-125 level (P<0.172). Overall survival revealed significant survival difference between patients whose tumor showed Ki-67 overexpressions compared with remaining patients. Conclusions: Ki-67 overexpressions was a poor prognostic indicator in epithelial ovarian carcinomas.

두경부 편평세포암종과 종양주변 점막에서의 Ki-67 표지지수

최건,유강목,유동희,채성원,정광윤,최종욱 대한이비인후과학회 1998 대한이비인후과학회지 두경부외과학 Vol.41 No.6

급성골수성백혈병에서 Ki-67 단클론항체를 이용한 세포주기 분석

안진석,김은실,김흥태,박선양,김병국 大韓血液學會 2002 大韓血液學會誌 Vol.37 No.3

후두와 하인두 편평세포암종에서 Ki-67표지지수와 Cyclin D1 발현의 예후적 의미

소상훈,송병철,정인교,노영수,임현준,김덕환 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.5

수술로 절제한 위장관기질종양에서 Ki-67 발현의 예후적 중요성

정성연 ( Seong Yeon Jeong ),박원우 ( Won Wo Park ),김유선 ( You Sun Kim ),박영일 ( Young Il Park ),김승협 ( Seung Hyup Kim ),윤원재 ( Won Jae Yoon ),문정섭 ( Jeong Seop Moon ),이병모 ( Byung Mo Lee ),홍성우 ( Seong Woo Hong ),강 대한소화기학회 2014 대한소화기학회지 Vol.64 No.2

목적: 현재까지 위장관기질종양(GIST)을 양성과 악성으로 분류할 수 있는 명확한 조직학적 기준은 없지만, 전이나 재발을 일으킬 수 있는 위험도를 종양세포의 유사분열 수와 종양의 크기를 기준으로 나누고 있다. Ki-67은 세포 증식의 표지자로 사용되는 단백질로, GIST의 예후 인자로의 가능성이 주목되고 있다. 이에 저자들은 수술 치료를 시행한 GIST 환자 중 Ki-67 면역조직화학염색을 시행한 32예의 Ki-67 지수와 유사 분열 지수와의 관련성, GIST의 재발률 및 무병 생존율에 대하여 분석 검토하여 보았다. 대상 및 방법: 인제대학교 서울백병원에서 수술 치료를 통하여 GIST를 제거한 32명의 환자를 대상으로 연구를 시행하였고 환자들의 의무기록을 통하여 성별, 연령, 증상 등의 임상적 특징과, 종양의 크기, 위치 등의 조직학적 특징 및 재발률에 대하여 조사하였다. 결과: NIH 진단기준으로 very low risk는 4예, low risk는 9예, intermediate risk는 14예, high risk는 5예였다. Ki-67 지수는 1-18%의 범위 내에 있었고, 평균은 5.56±4.48%였다. 평균 추적관찰 기간은 35.72±29.04개월이었고 관찰 도중 6 예(18.7%)에서 재발 혹은 전이가 발견되었다. Ki-67 지수가 5% 이하인 군의 누적 무병 생존율은 12개월, 24개월, 60개월에 각각 100%, 100%, 86%였다. 반면 Ki-67 지수가 5% 초과인 군의 누적 무병 생존율은 12개월, 24개월, 60개월에 각각 82.1%, 70.3%, 46.9%로 Ki-67 지수가 5% 이하인 환자에 비하여 무병 생존율에 유의한 차이를 보였다(p=0.007) 결론: Ki-67 지수가 5% 초과할 경우 GIST 재발의 고위험성을 시사한다. 향후 Ki-67 지수의 표준화와 치료 방향의 결정에 미치는 Ki-67 지수의 역할에 대한 연구가 필요하다. Background/Aims: Assessment of malignant potential in gastrointestinal stromal tumor (GIST) is still problematic. The maximum tumor diameter and the mitotic index are generally used as an index of malignancy of GISTs. The Ki-67 labeling index has recently been used as an index of cell growth. The aim of this study was to investigate the prognostic value of K -67 in GIST. Methods: We retrospectively reviewed the medical records of 32 patients with GIST who underwent surgical resection at Inje University Seoul Paik Hospital. We analyzed their Ki-67 expression, histologic finding, and prognosis. Results: According to the tumor size and mitotic count, 4 patients were classified as very low risk, 9 patients as low risk, 14 patients as intermediate risk and 5 patients as high risk. The average Ki-67 index was 5.56±4.48%. The median follow-up duration was 35.72±29.04 months, and local/distant recurrences were observed in 6 (18.7%) patients. The overall cumulative disease free survival rates in patients with Ki-67 index ≤5% at 1 year, 2 years, and 5 years were 100%, 100%, and 86%, respectively. The overall cumulative disease free survival rates in patients with Ki-67 index >5% were at 1 year, 2 years, and 5 years were 82.1%, 70.3%, and 46.9%, respectively. There was significant relationship between elevated Ki-67 and disease free survival rate (p=0.007). Conclusions: Our study suggests that Ki-67 index >5% confers a higher risk of relapse in patients with GIST. Future work should focus on standardization of Ki-67 assessment and specification of its role in making treatment decisions.(Korean J Gastroenterol 2014,64:87-92)

악성림프종에서 Argyrophilic Nucleolar Orgnizer Region과 Ki-67의 발현

이희정,이안희,이교영,강창석,심상인,김병기 대한병리학회 2000 Journal of Pathology and Translational Medicine Vol.34 No.4

Expression of the p16INK4a and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection

남은지,김재욱,홍종욱,장형선,이상엽,장시영,이대우,김상운,김재훈,김영태,김성훈,김종욱 대한부인종양학회 2008 Journal of Gynecologic Oncology Vol.19 No.3

Objective: The purposes of this study were to evaluate the expression of p16INK4a (referred as to p16) and Ki-67 in cervical intraepithelial neoplasia (CIN), and the correlation between high-risk human papillomavirus (HPV) infection and the above biomarkers. Methods: We analyzed 31 patients who were diagnosed with CIN at Kwandong University Myongji Hospital from October 2006 to September 2007. CIN specimens (CIN1, 12; CIN2, 6; CIN3, 13) were obtained by colposcopydirected biopsy (CDB) or loop electrical excision procedure (LEEP). The expressions of p16 and Ki-67 were evaluated by immunohistochemical methods with antibodies to p16 and Ki67. The immunohistochemical staining results were classified into four grades: 0, 1, 2 and 3. HPV genotyping or Hybrid Capture-II test was used to detect high-risk HPV. Results: The expression of p16 (p<0.001) and Ki-67 (p=0.003) were positively associated with CIN grade. p16 expressions increased significantly with high-risk HPV infection (p=0.014), especially HPV type 16 and 58. Ki-67 expression was not related with high-risk HPV. There was positive correlation between the expression of the p16 and Ki-67 (p=0.007). Conclusion: CIN grade were positively related to the expression of p16 and Ki-67. p16 expressions of high-risk HPV specimens significantly increased more than Ki-67. Therefore, in the diagnosis of CIN and high-risk HPV infection, p16 can be a useful biomarker. Objective: The purposes of this study were to evaluate the expression of p16INK4a (referred as to p16) and Ki-67 in cervical intraepithelial neoplasia (CIN), and the correlation between high-risk human papillomavirus (HPV) infection and the above biomarkers. Methods: We analyzed 31 patients who were diagnosed with CIN at Kwandong University Myongji Hospital from October 2006 to September 2007. CIN specimens (CIN1, 12; CIN2, 6; CIN3, 13) were obtained by colposcopydirected biopsy (CDB) or loop electrical excision procedure (LEEP). The expressions of p16 and Ki-67 were evaluated by immunohistochemical methods with antibodies to p16 and Ki67. The immunohistochemical staining results were classified into four grades: 0, 1, 2 and 3. HPV genotyping or Hybrid Capture-II test was used to detect high-risk HPV. Results: The expression of p16 (p<0.001) and Ki-67 (p=0.003) were positively associated with CIN grade. p16 expressions increased significantly with high-risk HPV infection (p=0.014), especially HPV type 16 and 58. Ki-67 expression was not related with high-risk HPV. There was positive correlation between the expression of the p16 and Ki-67 (p=0.007). Conclusion: CIN grade were positively related to the expression of p16 and Ki-67. p16 expressions of high-risk HPV specimens significantly increased more than Ki-67. Therefore, in the diagnosis of CIN and high-risk HPV infection, p16 can be a useful biomarker.