Prognostic Significance Of Ki-67 Expression Research Articles

Prognostic significance of Ki-67 expression in breast cancer patient

Prognostic significance of Ki-67 expression in breast cancer patient

Prognostic Significance of Ki67 Expression By Immunohistochemistry (IHC) on Bone Marrow Biopsy in Newly Diagnosed Multiple Myeloma

Background: Multiple myeloma (MM) is known to be a heterogeneous disease encompassing several molecular subtypes that can be defined either by means of genetic or molecular testing. In the multigene tests, the ‘PR’ subtype enriched with proliferation-related genes has a substantial impact on the prediction of the risk of MM recurrence. Ki-67 is a nuclear protein involved in cell cycle regulation and is considered an indicator of proliferation. It is present in dividing cells during all active phases of the cell cycle (S, G1, G2 and mitosis phases) and is distinctly absent in resting or quiescent (G0) cells. Ki67 expression has been widely used as an index to evaluate the proliferative activity of breast cancer and lymphoma but the impact of Ki-67 expression on the clinical outcomes of patients with MM has largely been unexplored. This study aimed to investigate whether Ki-67 expression by IHC is an indicator of outcome in MM patients, especially those treated with novel therapies combined with or without autologous stem cell transplantation.Methods: The MM database was interrogated from January 2012-May 2017 for all newly diagnosed symptomatic MM subjects with Ki67 expression levels estimated by IHC on bone marrow biopsy specimens at diagnosis. Clinical features and outcomes were captured and compared between the cohorts of Ki67 high (Ki67-hi) subjects (Ki67 >5%) and Ki67 low (Ki67-lo) subjects (Ki67 ≤5%). Continuous variables were compared using median two sample tests, while incidences and proportions were compared using Fisher's exact tests. Survival distributions were estimated with Kaplan Meier techniques and compared between Ki67 cohorts using log-rank tests. Differences in overall survival (OS) and progression free survival (PFS) between the positive and negative cohorts were quantified with hazard ratios from Cox regression. Model selection was performed to determine adjusted hazard ratiosResults: A total of 125 MM subjects were identified with Ki67 values at diagnosis (26 Ki67-hi, 99 Ki67-lo). Gender, race, and age were similar between the two cohorts. There were no significant differences in beta-2 microglobulin (B2M) or LDH levels between the cohorts (p=0.236 and p>0.999, respectively); however, the median B2M in the Ki67-hi cohort was numerically higher than in the Ki67-lo cohort (4.6 vs 3.5 mg/L). A significantly greater proportion of Ki67-lo subjects had good risk cytogenetics (58.3%) compared to those who were Ki67-hi subjects (32.0%, p=0.035). There were no significant differences in the tested flow cytometry immunophenotype markers except for CD38, which was expressed in 87.9% of the Ki67-lo cohort compared to 53.9% of the Ki67-hi cohort (p<0.001). OS was significantly worse in the Ki67-hi cohort (HR: 3.12, 95% CI: 1.25, 7.75, p=0.010). Additionally, after adjusting for age and adverse risk, the risk of death in the Ki67-hi cohort is 4 times that of the Ki67-lo cohort (p=0.004, 95%CI: 1.58, 10.29). PFS was worse in the Ki67-hi cohort (HR: 1.86; 95% CI: 0.94, 3.65; p=0.069). Median follow-up time was 21.9 months (IQR 9.7 - 30.7 months).Conclusions: Our early results demonstrate that elevated Ki67 expression measured by IHC staining is associated with worse OS in newly diagnosed MM. IHC staining for Ki67 can potentially be utilized in economically constrained healthcare settings globally. Our current work focuses on standardization of Ki67 assessment and specification of its role as a dynamic biomarker of the treatment effectiveness in newly diagnosed MM. [Display omitted] DisclosuresVoorhees:Amgen: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Oncopeptides: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy, Speakers Bureau. Usmani:Array BioPharma: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Research Funding. Bhutani:Amgen: Speakers Bureau; Prothena Therapeutics: Research Funding; BMS: Speakers Bureau; Takeda Oncology: Speakers Bureau.

High Ki-67 expression is significantly associated with poor prognosis of ovarian cancer patients: evidence from a meta-analysis.

The prognostic significance of Ki-67 expression in patients with ovarian cancer was controversial in various studies. Therefore, we carried out a meta-analysis to determine the prognostic significance of Ki-67 in ovarian cancer patients. We searched PubMed, Cochrane Library, EMBASE, Web of Knowledge, China National Knowledge Infrastructure database and WanFang digital database for eligible studies from January 1, 1990 to June 1, 2017. The pooled hazard ratios and 95% confidence intervals were calculated to assess the prognostic significance of Ki-67 expression for overall survival in ovarian cancer patients. Finally, 38 eligible studies and 5004 ovarian cancer patients were included in the current study. The pooled hazard ratio was 1.35 (95% confidence interval 1.24-1.46, P = 0.001) for overall survival in ovarian cancer patients. The funnel plot bias was obviously asymmetrical and Egger's test also detected significant publication bias (P = 0.001). The Contour-enhanced funnel plot with trim-and-fill method supplemented 11 dummy studies to balance the funnel plot and nine new supplementary studies were in area with statistical significance. Sensitivity analysis and cumulative meta-analysis further demonstrated that the association between high Ki-67 expression and poor overall survival of ovarian cancer patients was stable and reliable. High Ki-67 expression is significantly related to poor overall survival and may serve as a prognostic biomarker for ovarian cancer patients.

Inverse correlation between Ki67 expression as a continuous variable and outcomes in luminal HER2-negative breast cancer.

Few studies to date have investigated the prognostic significance of Ki67 expression as a continuous variable in breast cancer. This study aimed to evaluate the impact of Ki67 expression as a dichotomous or continuous variable on outcomes in estrogen receptor (ER)+ and human epidermal growth factor receptor 2 (HER2)- breast cancer. Survival analysis was performed to estimate the likelihood of distant recurrence and death in retrospective data from 794 patients with ER+/HER2- breast cancer. We assessed the relationship between outcomes and two Ki67 cutoffs, 14% and 20%, and the Ki67 labeling index as a continuous variable. In univariate analysis, T stage, lymph node involvement, histological grade, progesterone receptor status, and Ki67 expression at the two cutoffs and as a continuous variable were identified as significant prognostic factors for distant disease-free survival (DDFS) and overall survival (OS). There were no statistical differences in DDFS and OS between women with Ki67 expression of <14% and 14-<20%. Multivariate analysis showed that Ki67 expression ≥20% was an independent prognostic indicator for DDFS. Regarding the risk of distant metastasis, the 20% cutoff was more reliable than 14%. We also found that Ki67 expression as a continuous variable was an independent prognostic factor for DDFS and OS in multivariate analyses. High Ki67 expression is associated with a survival disadvantage in patients with ER+/HER2- breast cancer, indicating that these patients might have a higher risk of recurrence after primary treatment and might therefore benefit from individualized treatment.

Prognostic significance of Ki67 expression and the derived neutrophil-lymphocyte ratio in nasopharyngeal carcinoma.

PurposeTo investigate the association of pretreatment Ki67 expression and the derived neutrophil–lymphocyte ratio (dNLR) with clinical outcomes in nasopharyngeal carcinoma (NPC).Patients and methodsFor the study, 46 patients diagnosed with NPC at our hospital were recruited between April 2013 and December 2015. All patients were histologically confirmed to have non-keratinizing undifferentiated NPC. The expression of Ki67 proteins in NPC tissue was analyzed immunohistochemically, and the dNLR was assessed in the peripheral blood, both before treatment. Stage I and II disease was treated with radiotherapy with or without concurrent chemotherapy, and stage III and IV disease was treated with cisplatin-based radiochemotherapy and neoadjuvant chemotherapy regimens.ResultsForty-five of the 46 patients met the criteria, and the median follow-up period was 41 months (15–56 months). The cutoff values for Ki67 and dNLR were 77.5% and 2.01%, respectively. The 3-year overall survival (OS) and progression-free survival rates in the high versus low Ki67 expression groups were 62.5% vs. 93.1% (P = 0.009) and 56.3% vs. 93.1% (P = 0.003), respectively. The 3-year OS rate of patients with high dNLR vs. low dNLR was 64.3% vs. 90.3% (P = 0.023). In the Cox risk ratio model, Ki67 expression and dNLR were independent prognostic factors for OS. Patients were then divided into three groups based on Ki67 expression and dNLR (high risk, both factors were high; intermediate risk, one factor was high; and low risk, neither factor was high). The 3-year OS rates were 20%, 85%, and 95% for the high, intermediate, and low risk groups, respectively (P < 0.001).ConclusionPretreatment Ki67 and dNLR levels can be used as independent prognostic markers in NPC, and elevated values are associated with poor prognosis. Concurrently, high Ki67 expression and dNLR predict a significantly adverse outcome.

Ki-67 expression predicts biochemical recurrence after radical prostatectomy in the setting of positive surgical margins

BackgroundPositive surgical margin (PSM) is a predictor of biochemical recurrence (BCR) following radical prostatectomy (RP). Attempts to stratify PSM based on linear length, Gleason score, location and number have failed to add to predictive models using margin status alone. We evaluated the prognostic significance of Ki-67 expression in this setting.MethodsImmunohistochemical staining for Ki-67 was done on prostatectomy specimens from 117 patients who had a PSM. Ki67 expression was measured at the margin and in the index lesion. Patients were dichotomized based on Ki-67 expression into three groups. Group 1 with no Ki-67 expression, Group 2 with Ki-67 ≤ 2%, and Group 3 with Ki-67 ≥ 3%.To eliminate the impact of the adjuvant treatment (AT) on the outcome, data were analyzed by the Cox proportional hazards in which AT was Considered as a time-dependent covariate.ResultsThe discordance rate of Ki-67 expression between matched index lesion and margin specimens was 44/117 (37.6%). There was a trend for higher risk of BCR (HR:2.06, (0.97–4.43), P = 0.06) in patients expressing high Ki67 at the surgical margin although this was not statistically significant. However High Ki-67 expression in the index lesion was an independent predictive factor for BCR in this subset of patients. (HR:4, (1.64–9.80), P = 0.002).ConclusionHigh Ki67 expression in the index prostate cancer lesion is an independent predictor of BCR in patients with positive surgical margin following radical prostatectomy. Our findings need to be validated in a larger cohort.

Abstract P5-08-23: Ki-67 expression is not a valuable predictive prognostic factor when progesterone receptor expression is high in estrogen receptor-positive breast cancer

Abstract Background Immunohistochemistry markers are recognized as a predictive prognostic factor for women with breast cancer. Ki-67 and progesterone receptor (PgR) expression are reported to be independently associated with breast cancer prognosis. Some studies report high Ki-67 expression as a negative predictive marker. Whereas other studies report tendency of similar survival between high and low Ki67 cancers when PgR expression is high. In this study, we examined the prognostic significance of Ki-67 expression under PgR expression status. Methods The records of 2,366 patients were retrospectively reviewed. The patients underwent surgery for primary breast cancer from July 2009 to December 2012 at a single institution. We studied the prognostic significance of Ki-67 expression under PgR expression. We used 20% and 10% as the cut-off value for PgR and Ki-67, respectively. The end point was recurrence-free survival (RFS) evaluated by use of Kaplan-Meier analysis. Result Of the 2,366 analyzed patients, the median follow-up time was 43 months. During follow-up, 44 patients had recurrence, loco-regional recurrence developed in 23 patients and distant recurrence developed in 21 patients. In patients with low PgR expression, high Ki-67 expression group showed significantly worse prognosis compared to low Ki-67 expression group (p=0.005). On the other hand, no significant difference was shown between low and high Ki-67 expression group when PgR expression was high (p=0.637). Also multivariate analysis demonstrated that high Ki-67 expression was an independent prognostic factor only when PgR expression was low. (95% confidence interval [CI], 1.35-10.48; p=0.011) Conclusion This is the largest reported study that prognostic significance of Ki-67 expression is defined by PgR expression. Our study presents that high Ki-67 expression is inversely correlated with recurrence risk in early breast cancer patients only under low PgR expression. At high PgR expression, Ki-67 expression has no influence on breast cancer prognosis. Therefore, attention should be paid to correlation between PgR and Ki-67 expression. Citation Format: Han JH, Kang YJ, Han W, Lee H-B, Kim Y, Yoo T-K, Moon H-G, Noh D-Y. Ki-67 expression is not a valuable predictive prognostic factor when progesterone receptor expression is high in estrogen receptor-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-23.

What is the Prognostic Significance of Ki-67 Positivity in Oral Squamous Cell Carcinoma?

BACKGROUD: Numerous studies have stated that Ki-67 is a good prognostic marker in oral squamous cell carcinoma (OSCC). However, some researchers believe the contrary. To address this controversy, we performed a systematic literature retrieval to estimate the prognostic significance of Ki-67 expression in patients with OSCC. METHODS: Databases covering Pubmed, Ovid, Web of Science, Embase and the Cochrane library were searched regardless of publication year. Overall survival (OS), local recurrence (LR) and disease-free survival (DFS) were the main outcome measures. Relative risks (RRs) and its 95% confidential intervals (CIs) were used for statistical analysis. RESULTS: Twenty-seven articles with 2146 patients were included in this study. The results of the meta-analysis suggested that the pooled RRs and its CIs for OS, LR, and DFS were 1.45 (1.15 - 1.84), 1.76 (0.74 - 4.16) and 1.52 (1.07 - 2.14), respectively. However, the heterogeneities of OS and LR were obvious (I-squared (OS) = 59.4%, I-squared (LR) = 72.6%). After subgroup analysis based on systemic treatment, the cut-off value of Ki-67 expression, ethnicity and types of antibody, the heterogeneities became acceptable. It was observed that systemic treatment, cut-off values of Ki-67 expression, ethnicity and the types of antibody affected the results. The statistical analyses of subgroups suggested that non-systemic treatment, (OR=1.77, 95% CI = 1.39-2.25, p = 0.000) and Asian populations (OR=2.09, 95% CI = 1.32-3.32, p = 0.002) are high risks for Ki-67 high expression, and low cut-off value of Ki-67 expression (OR = 1.44, 95% CI = 1.001-2.072), MIB-1 antibody (OR = 1.48, OR 95% = 1.10-1.99) might affect the identification of results. CONCLUSIONS: According to this meta-analysis, high Ki-67 expression might be a negative prognostic marker of patients with OSCC, especially in Asian populations. In addition, Ki-67 expression affects the treatment response.

Ki67 Expression has Prognostic Significance in Relation to Human Papillomavirus Status in Oropharyngeal Squamous Cell Carcinoma.

Human papillomavirus (HPV) is the major predictor of outcome in oropharyngeal squamous cell carcinoma (OSCC) but the disease is heterogeneous and there is limited understanding of the prognostic significance of other molecular markers in relation to HPV. This multi-institutional, retrospective study examined the prognostic significance of Ki67 expression in association with HPV status in OSCC. The 105 patients recruited had a median follow-up of 70 months. Tumor HPV status was determined by HPV E6-targeted multiplex real-time polymerase chain reaction/p16 semiquantitative immunohistochemistry and Ki67 expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox regression with censoring at dates of last follow-up. HPV and Ki67 positivity rates were 46 and 44 %, respectively. HPV-positive cancers were more likely to be Ki67-positive. On multivariate analysis, both HPV and Ki67 were predictors of outcome. Ki67-positive cancers were associated with a 3.13-fold increased risk of disease-related death compared with Ki67-negative cancers. Among HPV-negative patients, Ki67-positive disease was associated with 5.6-fold increased risk of oropharyngeal cancer-related death (p = 0.002), 5.5-fold increased risk of death from any cause (p = 0.001), and 2.9-fold increased risk of any event (p = 0.013). The risk of locoregional failure was lowest in patients with HPV-positive/Ki67-positive cancers. Ki67 predicts disease-related death in oropharyngeal cancer independent of HPV status. A combination of Ki67 and HPV status provides improved prognostic information relative to HPV status alone. Our data suggest, for the first time, that Ki67 status has prognostic value, particularly in HPV-negative oropharyngeal cancer.

Ki-67 is a valuable prognostic predictor of lymphoma but its utility varies in lymphoma subtypes: evidence from a systematic meta-analysis

BackgroundKi-67 is a nuclear protein involved in cell proliferation regulation, and its expression has been widely used as an index to evaluate the proliferative activity of lymphoma. However, its prognostic value for lymphoma is still contradictory and inconclusive.MethodsPubMed and Web of Science databases were searched with identical strategies. The impact of Ki-67 expression on survival with lymphoma and various subtypes of lymphoma was evaluated. The relationship between Ki-67 expression and Diffuse Large B Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL) was also investigated after the introduction of a CD-20 monoclonal antibody rituximab. Furthermore, we evaluated the association between Ki-67 expression and the clinical-pathological features of lymphoma.ResultsA total of 27 studies met the inclusion criteria, which comprised 3902 patients. Meta-analysis suggested that high Ki-67 expression was negatively associated with disease free survival (DFS) (HR = 1.727, 95% CI: 1.159-2.571) and overall survival (OS) (HR = 1.7, 95% CI: 1.44-2) for lymphoma patients. Subgroup analysis on the different subtypes of lymphoma suggested that the association between high Ki-67 expression and OS in Hodgkin Lymphoma (HR = 1.511, 95% CI: 0.524-4.358) was absent, while high Ki-67 expression was highly associated with worse OS for Non-Hodgkin Lymphoma (HR = 1.777, 95% CI: 1.463-2.159) and its various subtypes, including NK/T lymphoma (HR = 4.766, 95% CI: 1.917-11.849), DLBCL (HR = 1.457, 95% CI: 1.123-1.891) and MCL (HR = 2.48, 95% CI: 1.61-3.81). Furthermore, the pooled HRs for MCL was 1.981 (95% CI: 1.099-3.569) with rituximab and 3.123 (95% CI: 2.049-4.76) without rituximab, while for DLBCL, the combined HRs for DLBCL with and without rituximab was 1.459 (95% CI: 1.084-2.062) and 1.456 (95% CI: 0.951-2.23) respectively. In addition, there was no correlation between high Ki-67 expression and the clinical-pathological features of lymphoma including the LDH level, B symptoms, tumor stage, extranodal site, performance status and IPI score.ConclusionsThis study showed that the prognostic significance of Ki-67 expression varied in different subtypes of lymphoma and in DLBCL and MCL after the introduction of rituximab, which was valuable for clinical decision-making and individual prognostic evaluation.

Prognostic significance of Ki-67 expression in patients undergoing surgical resection for gastrointestinal stromal tumor

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 Ki-67 in GIST. 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. 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). 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.

Abstract P1-08-05: The prognostic significance of Ki-67 expression before and after neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes

Abstract Purpose This study was conducted to analyze the Ki-67 expression before and after neoadjuvant chemotherapy and clinical pathology characteristics of different biological breast cancer phenotypes at our center. A correlation study was performed between Ki-67 index change and the prognosis of different biological breast cancer phenotypes and prognosis in Northern China. Methods A regression analysis was performed on 213 patients with invasive breast carcinoma accepted NAC admitted to Tianjin Medical University Cancer Institute and Hospital of Breast Surgery from January 2007 to April 2008. These patients were subtyped by hormone receptor status and HER2 status.The Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. The prognostic value of the Ki-67 index for different biological breast cancer phenotypes disease-free survival (DFS) and overall survival (OS) was investigated by use of Kaplan–Meier curves and multivariable Cox regression. Results The overall pathologic CR (pCR) rate, defined as no invasive residuals in breast and axilla, was 17.8%. The highest pCR rate of 32.1% was observed in patients with HR-/HER2+ tumors, which is 11.4%, 20.0% and 26.2% in HR+/HER2- HR+/HER2-,HR+/HER2+and HR-/HER2- tumor respectively(P = 0.024).The Ki-67 expression of pre-NAC and post-NAC have prognostic significance in HER2- breast cancer, which have not significance different in HER2+ breast cancer:The best Ki-67 idex cut point of pre-NAC and post-NAC to predict long-term survival was respectively 20% and 10% in HR+/HER2- breast cancer. Moreover, patients with a higher Ki-67 index (&amp;gt; cut-off point) showed significantly lower 5year-DFS/OS rates compared with those whose Ki-67 index were below cut-off point. In addition, Ki-67 index of post-NAC were independent prognostic factors for 5 year disease-free survival of patients with HR+/HER2- breast cancer. Ki-67 change between pre- and post-NAC as an independent prognostic factor independently predict prognosis in the patients who have not achieved pCR, while the best cut-off point was 18%. Conclusion The Ki-67 index of pre- and post-NAC could predict the prognosis in the patients with HER2- breast cancer. Moreover, the Ki-67 change between pre- and post-NAC was an independent prognostic factor in the patients who have not achieved pCR. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-05.

Prognostic Significance of Ki-67 Expression in Rectal Carcinoid Tumors

Rectal carcinoid tumors can be resected with endoscopy, and it is important to assess their prognostic factors. We evaluated the potential of Ki-67 expression as a prognostic factor in rectal carcinoid tumors. We retrospectively reviewed the medical records of 37 patients with rectal carcinoid tumors who got endoscopic resection from January 2001 to January 2011 at Inje University Seoul Paik Hospital. We analyzed their endoscopic and histologic findings, Ki-67 expression, clinical outcome, and prognosis. The mean age (±SD) of the patients was 56.3±10.7 years, and the male : female ratio was 3.6 : 1. The mean tumor size was 0.5±0.4 cm, 33 patients showed grade 1 tumors (89.2%) and the average Ki-67 expression was 0.7±1.2%. Thirty five patients underwent endoscopic mucosal resection, and two required endoscopic submucosal dissection. Eight patients had positive margins after resection, but no cases of lymphovascular invasion were identified. The median follow-up duration was 21.4±25.4 months, and no recurrences were observed. In low grade rectal carcinoid tumors which are lack of central depression on colonoscopy, the expression of a molecular marker of malignant potential, Ki-67, was low. Therefore, endoscopic resection seemed to be a safe and effective treatment for these tumors.

The value of Ki-67 antigen expression in tissue microarray method in prediction prognosis of patients with endometrioid endometrial cancer

To assess the prognostic significance of Ki-67 expression in the tissue microarray method (TMA) for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). The study examined 159 consecutive patients aged 37-86 (62.82 +/- 9.95) with EEC stages I-III according to FIGO, treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards they were subsequently treated and examined at the Regional Cancer Center Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery and constructed into the TMA recipient blocks. Using TMA method, the relationship between Ki-67 expression, DFS and OS was examined. DFS was defined as a period from primary surgery until relapse. OS was defined as a period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE; KE/1673/12). The follow-up time varied between 3-60 months (51.42 +/- 15.87). In 31 patients (19.50%) the relapse of was diagnosed 1-59 months (24.97 +/- 16.08) after commencement of the treatment. During follow-up 32 patients (20.12%) died. DFS and OS were 80.50% and 79.88%, respectively The lack of Ki-67 expression was found in 37 cases (23.27%) while in 122 patients (76.73%) the expression was present (p < 0.001). The expression of Ki-67 in 1-10%, 11-20% and > 20% was present in 76 cases, 26 cases and 20 cases, respectively Positive correlation between the expression of Ki-67 and staging was present (r = 0.353; p < 0.001). In EEC patients with no relapse diagnosed during follow-up the expression of Ki-67 was present in 7.63 +/- 7.57% of EEC cells, when compared to 23.06 +/- 22.93% in EEC patients in relapsed disease (p < 0.001). The relationship between increased Ki-67 expression and increased grading was not statistically significant (r = 0.149; p = 0.061). The expression of Ki-67 did not depend on patient age (r = 0.040; p = 0.617). In univariate analysis negative correlation was found between the expression of Ki-67 and DFS (p < 0.001) and OS (p = 0.01). In multivariate analysis worse DFS was related to higher staging of EEC (p < 0.0 01) and increased expression of Ki-67 (p < 0.001). Worse OS was related to higher staging in multivariate analysis (p < 0.001). Ki-67 expression was not related to OS in multivariate analysis. Age of patients and grading of the EEC were not related to DFS and OS. The expression of the Ki-67 can significantly affect therapeutic decisions in selected EEC patients. The high Ki-67 expression in EEC patients is related to increased risk of relapse. The TMA technique is a good method for the assessment of the Ki-67 in studies conducted in EEC patients and makes it easier to carry out immunohistochemistry in large populations of patients.

Basal Ki67 expression measured by digital image analysis is optimal for prognostication in oral squamous cell carcinoma

AimThe prognostic significance of Ki67 expression in cancers, including oral squamous cell carcinoma (OSCC), is unclear. This may be partly attributed to the lack of consensus surrounding the optimal approach for measuring tumour Ki67 expression. The aim of this study was to evaluate the association between different measures of Ki67 expression and disease-specific survival (DSS) in OSCC. MethodsTissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded (FFPE) pre-treatment tumour tissue obtained from 121 OSCC patients diagnosed between 1998 and 2006. Ki67 expression was quantified using fluorescence immunohistochemistry (IHC) and AQUAnalysis® in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Intensity and percentage-based approaches for Ki67 scoring were tested for their association with survival. ResultsKi67 scores obtained from intensity and percentage-based approaches had similar associations with prognosis. We also found that high basal (lowest observed in triplicate cores) Ki67 expression was more strongly associated with improved 5-year disease-specific survival than hot-spot and average Ki67 measurements. The association of high basal Ki67 expression with improved prognosis was most pronounced in patients who received postoperative radiation. Cox proportional hazards analysis showed that the basal Ki67 expression is an independent prognostic marker in our OSCC cohort when adjusted for pathological T-stage, nodal status and treatment. ConclusionsOur study provides a framework for reaching a consensus on the optimal approach for measuring Ki67 expression in cancers. Our results suggest that rigorous comparisons of measurement approaches should be applied in a tumour-type and treatment-specific manner to enhance the clinical application of Ki67 assessment.

P177 The prognostic significance of Ki-67 expression in patients with early invasive breast cancer

P177 The prognostic significance of Ki-67 expression in patients with early invasive breast cancer

Prognostic Significance of Ki-67 Expression in Extranodal NK/T Cell Lymphoma, Nasal Type: A Proposed Prognostic Index, KLABS Index.

Ki-67 is a nuclear antigen expressed by dividing cells, therefore, the percentage of Ki-67-positive cells reflects the proportion of tumor cells actively proliferating. However, the prognostic value of Ki-67 expression is still controversial in non-Hodgkin's lymphoma. Although a recent study in peripheral T-cell lymphoma showed a positive correlation with poor prognosis, the prognostic value of Ki-67 has never been studied in patients with extranodal NK/T cell lymphoma. Therefore, we performed this study to determine the value of Ki-67 expression in predicting prognosis and to propose a new prognostic model involving Ki-67 expression in patients with extranodal NK/T cell lymphoma. We studied 65 patients who were diagnosed with extranodal NK/T cell lymphoma from 1999 to 2005. All patients were treated with combination chemotherapy alone or followed by radiotherapy. We analyzed the percentage of Ki-67 expressing cells and determined its prognostic significance in terms of overall survival (OS) and disease-free survival (DFS). The immunohistochemical staining of Ki-67 was available for this study in fifty-five patients. The median age was 41 (range: 19 – 74 years), 89.1 percent of the patients (49/55) had an ambulatory performance status: Eastern Cooperative Oncology Group (ECOG) 0–1. Fifty-one patients presented as a localized disease: Ann Arbor stage I or II, and elevated level of serum lactate dehydrogenase (LDH) was observed in 14 patients. Thus, most patients showed the low or low-intermediate international prognostic index (IPI): low risk (74.5%, 41/55) or low intermediate risk (18.2%, 10/55). The percentage of Ki-67 expressing tumor cells was ranged from 5% to 95%, and the patients were separated into two groups: low Ki-67 (< 50%) versus high (≥ 50%). The patients in the high Ki-67 group had a shorter OS (95% CI 1.0-6.3, P = 0.046) and DFS (95% CI 1.1-5.5, P = 0.024) while the IPI failed to predict worse OS. Ki-67 expression could also predict the group with worse prognosis in 51 patients of low and low-intermediate IPI risk. Age, serum LDH, B symptoms, and tumor size were also associated with worse OS or DFS. Thus, based on the univariate and mutivariate analysis, we proposed a new prognostic index (KLABS index) with high Ki-67 expression, increased serum LDH, Age (≥ 60 years), presence of B symptoms, and bulky Size of tumors (≥ 10cm2) as follows: low risk, none or one of the above-mentioned factors; intermediate risk, presence of two factors; high risk, presence of three or more factors. This new index showed a high degree of correlation with survival outcomes in terms of OS and DFS (Figure A, B). This study demonstrated the prognostic significance of Ki-67 expression, and our new prognostic index may become a useful tool for predicting prognosis in extranodal NK/T cell lymphoma, nasal type. [Display omitted]

Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treated by total laryngectomy.

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in laryngeal squamous cell carcinomas. Ki-67 labeling was quantified in 63 laryngeal squamous cell carcinomas by counting at least 1,000 tumor cells in the most immunoreactive area in each sample, and the Ki-67 labeling index was calculated as a percentage. The antigen expression was compared with clinical factors, histopathological grading and prognosis. The Ki-67 mean proliferation index for all patients was 25.44% ( range, 2-75%). A significant correlation was found between Ki-67 mean proliferation index and patient age ( P<0.05), T-stage ( P<0.05), nodal metastasis ( P=0.001) and recurrence ( P<0.001). There was no significant association between the Ki-67 mean proliferation index and tumor site or histologic grade. A univariate analysis showed that the Ki-67 labeling index >21% ( P<0.001), T-stage ( P<0.001) and nodal metastasis ( P=0.001) are determinants of recurrence. In the multivariate analysis, the Ki-67 labeling index >21% ( P<0.001), T-stage ( P<0.001) and nodal metastasis ( P<0.05) were independent predictors of recurrence. Kaplan-Meier plots of survival in patients with Ki-67 values above and below the median (21%) of the general study population showed that a high Ki-67 labeling index correlated with a shorter disease-free survival ( P<0.0001). The analysis of the Ki-67 labeling index at the time of initial surgery may be a powerful prognostic marker for patients with laryngeal squamous cell carcinoma and may be useful for selecting subgroups of patients who should be treated with more aggressive therapies.

The Ki-67 index and survival in non-small cell lung cancer: a review and relevance to positron emission tomography.

We reviewed the current literature to discover the range of studies covering tissue-based and noninvasive methods for determining tumor stage and the prognostic value of staging in non-small cell lung cancer. Despite refinements in staging of non-small cell lung cancer, each stage remains heterogeneous because each stage contains patients who are at higher risk for recurrence than other patients within the same stage. Tissue-based and noninvasive methods have been investigated to complement tumor stage in assessing non-small cell lung cancer prognosis. The prognostic significance of tumor proliferation assessed by Ki-67 protein expression has been demonstrated in non-small cell lung cancer. Recent positron emission tomography studies have also shown both prognostic value in non-small cell lung cancer uptake of [F-18] fluorodeoxyglucose (FDG) and correlation between non-small cell lung cancer FDG uptake and tumor proliferation. We reviewed the prognostic significance of Ki-67 expression in non-small cell lung cancer and related it to positron emission tomography.

Prognostic significance of Ki-67 expression in advanced prostate cancer in relation to disease progression after androgen ablation

Correspondence to Mr Christopher R. Chapple, Urology Research Department, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK. Tel: +44 114 271 2791; fax: +44 114 279 8318