Cell Proliferation Assessed by Ki-67 Immunoreactivity on Formalin Fixed Tissues is a Predictive Factor for Survival in Prostate Cancer

Purpose

Proliferation rate may be an important determinant of tumor progression. To evaluate the predictive value of proliferation, immunoreactivity for the proliferation associated antigen Ki-67 was related to survival in a series of patients with prostate cancer.

Materials and Methods

Formalin fixed tissues, obtained by transurethral resection from 125 previously untreated prostate tumors, was examined with an immunohistochemical method for Ki-67. Ki-67 index was defined as the percentage of immunoreactive cells in a tumor. Patients were followed with surveillance after transurethral resection. The cause of death was determined by examination of patient records 11 to 19 years postoperatively (mean followup 71 months). At evaluation 17 patients (14%) were still at risk and 55 (44%) had died of prostate cancer.

Results

Mean Ki-67 index was 2.1 Ki-67 index correlated with grade (p <0.0005) and weakly with stage (p = 0.019). Mean survival of patients with a Ki-67 index of more than 3 was less than half that of patients with a Ki-67 index of less than 3 (53 versus 132 months, p <0.0005). The difference in survival remained in an analysis of the intermediately differentiated tumors (61 versus 126 months, p = 0.0032). In a Cox multiple regression analysis for cancer specific survival, including Ki-67 index, grade, stage, metastasis and age, Ki-67 index remained an independent predictive factor.

Conclusions

Our study indicates that proliferation rate, assessed by Ki-67 immunoreactivity in formalin fixed tissues, is a predictive marker for outcome in prostate cancer.     

The progression potential of peritoneal dissemination nodules from gastrointestinal tumors

It is necessary to examine the characteristics of the dissemination nodules to establish a therapeutic strategy for peritoneal dissemination from digestive malignancy. Ki-67 expression as a proliferation marker in peritoneal dissemination nodules was investigated. The subjects were 15 patients with gastrointestinal cancers who underwent resection of the primary tumor and disseminated nodules. The expression of Ki-67 in both primary tumor and peritoneal dissemination nodule from each patient was evaluated by immunohistochemistry. Ki-67 labeling index in the original tumor was higher than that in the disseminated nodule in 13 of 15 patients (P < 0.0001). The mean value of Ki-67 labeling index was 42.2% in the 15 original tumors and 18.7% in the 15 disseminated nodules. Proliferative activity in the disseminated nodules was lower than that in the primary tumors. Further examination about characteristics of cancer dissemination is needed to treat patients with peritoneal metastasis.     

原发性胃肠道恶性淋巴瘤的诊治

目的:探讨原发性胃肠道恶性淋巴瘤(PGIML)的诊治方法。方法:回顾性分析1995年1月—2010年12月收治的34例原发性胃肠道恶性淋巴瘤患者临床资料。结果:全组男23例,女11例,年龄22～74(平均51.8)岁。均经病理证实为恶性淋巴瘤,原发病灶位于胃24例,肠道10例。24例胃恶性淋巴瘤患者的首发症状为上腹部隐痛不适,8例合并呕血黑便,3例伴有发热;10例肠道淋巴瘤均以腹痛、腹部包块为首发症状,4例伴有黑便,2例有肠梗阻表现,肠穿孔1例。本组24例胃恶性淋巴瘤中,仅5例经术前胃镜病理活检证实;10例肠道恶性淋巴瘤中,仅1例经结肠镜活检确诊,术前确诊率仅17.64%(6/34)。误诊时间2～8(平均4.5)个月。患者均接受手术治疗,其中行根治性肿瘤切除术32例(根治性全胃切除术8例,根治性远端胃大部切除术14例,小肠部分切除术3例,右半结肠切除术6例,根治性直肠切除术1例),姑息性远端胃大部切除术2例。术后31例患者进行了化疗。34例患者免疫组化分型属B淋巴细胞型27例,T淋巴细胞型4例,未分类型3例。全组均获随访,随访时间5～62个月,1,3,5年生存率分别为82.35%,64.71,47.05%。结论:原发性胃肠道恶性淋巴瘤术前确诊率低,胃肠镜及病理活检是术前确诊的主要方法,以手术化疗联合的综合治疗效果良好。     

原发性胃弥漫大B细胞淋巴瘤38例临床预后分析

目的探讨原发性胃弥漫大B细胞淋巴瘤(PG-DLBL)的外科手术治疗的意义。方法回顾性分析我院1996年1月至2007年12月经胃镜活检或手术病理证实的38例PG-DLBL患者的临床病理κ料,根据治疗情况分为手术联合化疗组㈦单纯化疗组,比较两组预后情况。结果手术联合化疗17例,单纯化疗21例。两组发病年龄、性别、肿瘤分期、肿瘤大小均无显著性差异,手术联合化疗组的5年生存率为56%,单纯化疗组为33%,差异无统计学意义(P=0.676)。单纯化疗组并发消化道出血1例。手术联合化疗组的完全缓解率为94.1%,单纯化疗组为81.0%(P=0.233)。结论手术不应是PG-DLBL的首选治疗措施。     

Pathological and clinical associations of Ki-67 defined growth fractions in human prostatic carcinoma.

Estimation of the growth fraction of 153 prostatic carcinoma specimens employing Ki-67 immunostaining was undertaken and its relationship to various clinical parameters investigated. In prostate specimens, the percentage of tumour nuclei expressing Ki-67 antigen was measured and assigned a Ki-67 score. It was observed that high Ki-67 scores were associated with the poorly differentiated tumours, the correlation of this proliferation marker with histological grade was found to be significant (P less than 0.001). No relationship was observed between the Ki-67 score of the primary tumour with either the patient's age or with the primary tumor stage (T category). The metastatic status of the patient at diagnosis and the Ki-67 score of the tumour were correlated (P less than 0.05), higher Ki-67 scores being associated with M1 disease. Life-table analysis of 86 patients who subsequently received androgen withdrawal therapy, was undertaken with reference to the various Ki-67 scores of their primary tumors. A statistically significant difference in survival times was observed in patients whose Ki-67 values were less than 1% (P less than 0.0001) when compared to those patients whose tumours expressed 1% and over Ki-67 positivity, the former having longer survival times. When patients were subdivided according to their metastatic status and similar life-table analyses were carried out, no statistical difference was found between survival times and Ki-67 scores in M0 staged patients. In the M1 population of patients, however, those patients whose tumours were negative for Ki-67 expression had significantly longer survival times than those patients whose tumours exhibited positive Ki-67 staining (P less than 0.01). Comparing M1 staged patients whose prostate tumor cells exhibited less than 1% Ki-67 positive nuclei with M1 staged patients whose prostate tumour cells contained 1% and higher Ki-67 stained nuclei, a significantly longer survival time was found in the former group of patients (P approximately 0.0001).     

The role of surgery in the treatment of primary gastric lymphoma

The present retrospective study of 23 patients with primary gastric lymphoma had the objective of determining the role of surgical treatment on survival. All patients were submitted to gastric resection with regional lymph node removal. Nine patients (39.1%) received supplementary treatment (chemotherapy and/or radiotherapy). According to the Kiel classification, the most frequent histological type was the centroblastic (29.1%), and most patients (60.9%) had a low-grade lymphoma. According to the Ann Arbor classification, modified by Musshoff and Schmidt-Vollmer, stages were IE in 52.1%, II1E in 8.7%, II2E in 13.1%, and IV in 26.1% of the cases. Mean survival was 29.3 months. The variables that influenced survival rates were age, advanced stage tumor, and receiving postoperative adjuvant therapy. Analysis of our cases suggests that complete lesion resection along with adjacent lymph nodes, and supplementary postoperative treatment is the best approach for a resectable primary gastric lymphoma.     

P53和Ki-67的表达变化与三阴性乳腺癌pCR的关系研究

目的探讨三阴性乳腺癌新辅助化疗前后P53和Ki-67的表达变化,及其与病理完全缓解率(pCR)间的关系。方法选取2016-01-2018-12间就诊的73例三阴性乳腺癌患者的病史及病理资料,均经空心针穿刺病理确诊,并接受表柔比星联合多西他赛新辅助化疗。8周期化疗后行乳腺癌改良或保乳根治术。探讨新辅助化疗前后P53和Ki-67表达变化及其与pCR间的关系。结果73例患者总体pCR为30.1%(22/73),其中P53阳性组pCR为38%(19/50)、Ki-67高表达组pCR为39.2%(20/51)、Ki-67高表达且P53阳性组pCR高达48.6%(17/35),明显高于其他组。化疗后P53阳性表达率及Ki-67表达率均明显下降,其中P53阳性组有21例转为阴性组,pCR达71.4%。结论结合化疗前后P53及Ki-67的表达变化有助于预测三阴性乳腺癌新辅助化疗的pCR。     

Assessment of tumor cell kinetics by monoclonal antibody Ki-67

The expression of Ki-67 antigen in 71 patients with advanced gastric cancer was studied by immunohistochemical technique. Immunohistochemical staining with Ki-67 produced clear labeling of a portion of tumor cell nuclei, and the nucleoli stained intensely. The Ki-67 labeling rates of the 71 specimens ranged from 7.7 to 70.5% (mean: 29.2%; standard deviation: 12.9%). There was no significant association between Ki-67 labeling rates and macroscopic type, peritoneal metastasis, or serosal invasion. The tumors showing high Ki-67 labeling rates (greater than 25%) are more likely to have liver metastasis and lymph node involvement. Larger tumors, with a diameter greater than 6 cm, more frequently showed high Ki-67 labelling rate than those with a diameter less than 6 cm. When the Ki-67 labeling rate and 9 clinicopathologic parameters, as conventional prognostic factors, were entered simultaneously into the regression model, nodal status and Ki-67 labeling rate emerged as independent prognostic factors. These results indicate that the in situ determination of the growth fraction by Ki-67 antibody may be a reliable prognostic marker of advanced gastric cancer.     

Is an aggressive surgical approach to the patient with gastric lymphoma warranted?

At the Mayo Clinic, from 1970 through 1979, 84 patients (52 males and 32 females) had abdominal exploration for primary gastric lymphoma. All patients were observed a minimum of 5 years or until death. The histologic findings for all 84 patients were reviewed. Forty-four patients had "curative resection," and 40 patients had either biopsy alone or a palliative procedure. The probability of surviving 5 years was 75% for patients after potentially curative resection and 32% for patients after biopsy and palliation (p less than 0.001). The operative mortality rate was 5% overall and 2% after potentially curative resection. Increased tumor size (p less than 0.02), increased tumor penetration (p less than 0.01), and lymph node involvement (p less than 0.02) decreased the probability of survival, whereas histologic classification did not affect survival. Radiation therapy after surgery did not significantly affect the survival rate for the entire group or the survival rate for patients who had potentially curative resection. Resectability was associated with increased patient survival--independent of other prognostic factors--when our experience was analyzed by the Cox proportional-hazards model (p less than 0.005). It was concluded that an aggressive surgical attitude in the treatment of primary gastric lymphoma is warranted. The role of radiotherapy remains in question.     

Ki-67抗原表达在良恶性嗜铬细胞瘤鉴别诊断中的意义

目的研究Ki-67抗原表达在良、恶性嗜铬细胞瘤鉴别诊断中的意义及其作为预测肿瘤生物学行为标志物的价值。方法采用免疫组织化学方法对57例临床确诊为良性（良性组,39例）或恶性（恶性组,18例）的嗜铬细胞瘤组织进行组织染色,检测Ki-67抗原在嗜铬细胞瘤组织中的表达,并综合分析得出阳性指数。对两组数据进行统计学分析。结果良性及恶性组Ki-67平均阳性指数分别为0．98％及3．78％,恶性组明显高于良性组。良性组中Ki-67阳性指数〉3％者占5.1％（2／39）,恶性组中占55．6％（10／18）,统计学分析两组数据差异具有统计学意义（P〈0．05）。以Ki-67阳性指数〉3％为标准,对诊断恶性嗜铬细胞瘤的准确度为82．5％、灵敏度为55．6％、特异度为94．9％、阳性预测值为83．3％、阴性预测值为82．2％。随访结果显示,Ki-67高表达者术后生存率低于低表达者。结论Ki-67抗原是检测肿瘤细胞增殖的良好标记,可用于鉴别良、恶性嗜铬细胞瘤,并对判断肿瘤的预后有着及其重要的意义。Ki-67阳性指数〉3％具有区别良、恶性嗜铬细胞瘤及预测肿瘤生物学行为的意义。     

Human telomerase reverse transcriptase (hTERT) and Ki-67 are better predictors of survival than established clinical indicators in patients undergoing curative hepatic resection for colorectal metastases

BACKGROUND: We evaluated hTERT and Ki-67 expression in patients who underwent curative resection of hepatic colorectal metastases to determine if these markers of cell proliferation correlated better with survival than an established scoring system that is based on clinical predictors. METHODS: Patients operated on between 1993 and 1997 whose survival time was known were analyzed. For each patient, the clinical prognostic score was derived on the basis of primary node status, disease-free interval, number of hepatic tumors, largest tumor, and carcinoembryonic antigen level, and tumor specimens were analyzed for Ki-67 and hTERT with use of standard immunohistochemical techniques. The immunohistochemical analysis was blinded to all patient characteristics. RESULTS: The study included 66 patients. Twenty-six survived less than 2 years after surgery, 19 survived 2-5 years, and 21 survived more than 5 years. Ki-67 positivity and hTERT positivity (labeling indexes greater than or equal to 50%) were observed in 24 patients and 23 patients, respectively. The clinical score did not predict survival, although there was a weak trend toward a lower score in patients with better survival. Both Ki-67 (P =.04) and hTERT (P =.0001) correlated better with survival than did the clinical score. CONCLUSIONS: In patients undergoing curative resection of hepatic colorectal metastases, hTERT and Ki-67 are better predictors of survival than is a score based on clinical features.     

The use of the Ki-67 marker in the pathological diagnosis of the epithelioid variant of renal angiomyolipoma

Objective:  Epithelioid angiomyolipoma (EAML) is a rare malignant variant of renal angiomyolipoma (AML). There were 34 cases of EAML reported in 25 studies (including this present study) over the past decade. About 68% were females and 32% males. The mean age was 40.1 years, 53% developed metastatic disease after nephrectomy, and eight patients had TSC. All cases are reported positive when stained with HMB-45 which also labels all classical AML. This study evaluates the use of Ki-67 (proliferation marker) in the pathological diagnosis of EAML and distinction from classical AML. Method:  Immunohistochemical reactions for Ki-67 were generated on multiple representative blocks of tissue obtained from two cases of HMB-45 positive EAML and four cases of classic AML and the percentage of positively staining cells estimated. Results:  Both cases of EAML were strongly positive for Ki-67 while all four classic AML were completely negative. Conclusion:  The Ki67 is a useful marker in which distinguishes the malignant epithelioid variant of AML from classic AML.     

新辅助化疗后乳腺癌组织中survivin和Ki-67的表达及意义

目的 探讨CTF方案新辅助化疗后乳腺癌组织survivin和Ki-67的表达及其临床意义.方法 应用免疫组化SABC法检测60例行新辅助化疗和60例未行新辅助化疗的乳腺癌组织中survivin 和Ki-67的表达水平.结果 新辅助化疗组survivin和Ki-67阳性率分别为36.7%和38.3%,明显低于对照组的71.7%和61.7%(均P＜0.05);新辅助化疗组survivin的表达与Ki-67表达呈正相关(r=0.47,P＜0.05).新辅助化疗组总有效率73.3%;化疗后部分缓解者survivin阳性率为18.2%,明显低于无效者的81.3%(P＜0.01);化疗后部分缓解者Ki-67阳性率为47.7%,低于无效者的56.3%(P＞0.05).结论 应用CTF方案新辅助化疗缓解率高,近期疗效明显.CTF化疗药物,可能通过抑制乳腺癌survivin表达而抑制肿瘤的增殖.     

Transition from meningeal melanocytoma to primary cerebral melanoma. Case report

The authors describe the first case of an intracranial transition of a melanocytoma into a primary malignant melanoma within a short time. A 37-year-old woman presented with progressive brainstem syndrome due to a tumor, originally diagnosed and treated 12 years earlier, that extended from the petroclival area to the anterior craniocervical junction. The histological workup following subtotal tumor resection of the initial tumor had revealed the typical features of a fibrous melanocytic meningioma without increased proliferation. Ten years after the patient had completed treatment for the melanocytic meningioma, control neuroimaging demonstrated growth of the residual tumor with compression of the brainstem. Another neurosurgical intervention revealed a dark tumor of hard consistency. At this time immunohistochemical examinations demonstrated melanocytic features (expression of vimentin, S100 protein, and melan A) of the lesion with focally increased proliferation (5% of Ki-67-positive cells) but no higher mitotic activity. Clinical signs of deterioration along with imaging-confirmed tumor progression precipitated another operation within 7 months. A neuropathological examination revealed epithelial and anaplastic changes and indicated that the MIB-1 indices were greater than 25%. Pleomorphic changes and a focal high mitotic activity led to the diagnosis of a primary cerebral malignant melanoma. The patient's later clinical course consisted of a rapid diffuse meningeal spread of the lesion throughout the entire brain and spine. Despite whole-brain and stereotactic radiation therapy as well as chemotherapy, the patient died 4 months after the last neuropathological diagnosis. Although grossly resembling a meningioma, melanocytomas lack the former's histological and immunohistochemical features. The biological behavior of a melanocytoma is variable and recurrence may happen after subtotal resection, but intracranial transition into a malignant melanoma has not been observed previously.     

The role of Ki-67 in predicting biological behavior of goblet cell carcinoid tumor in appendix

Background

The aim of this study was to examine the role of Ki-67, a cellular proliferation marker, in the prognosis of goblet cell appendiceal carcinoid tumor.

Methods

Twelve goblet cell appendiceal carcinoid tumors were stained with MIB-1, a monoclonal antibody of Ki-67, to assess their cell proliferation and correlations with clinical and histologic parameters.

Results

Among 12 patients studied, the mean MIB-1 index was 24%, with tumors ranging from .5 to 5.0 cm in size. No correlation was observed between tumor size and MIB-1 index. Two patients had metastatic disease on presentation (MIB-1 index 10% and 60%). All patients received surgical intervention according to extent of tumor invasion regardless of their MIB-1 index values. Median follow-up was 54 months, with a 75% follow-up rate and 1 death from metastasis. The overall survival rate was 76%, with a disease-specific survival rate of 87%.

Conclusions

Ki-67 had no prognostic significance for goblet cell carcinoid tumors and should not be used solely to determine treatment and surgical approach.     

Primary non-Hodgkin's lymphoma of the bile ducts mimicking cholangiocarcinoma

BACKGROUND: Primary non-Hodgkin's lymphoma (NHL) of the liver and bile duct mimicking cholangiocarcinoma is rare. METHODS: The clinical and radiologic features and the treatment of 2 patients with primary NHL of the bile ducts are presented and analyzed together with cases collected from a review of the English literature between 1966 and 2003. RESULTS: Fifteen patients with primary NHL, including our 2 patients, presented with clinical features mimicking cholangiocarcinoma. All had jaundice; 9 had systemic symptoms; 7 had abdominal pain; and 5 had mass lesions. All had biliary strictures as shown on cholangiography. Two patients were infected with human immunodeficiency virus-1. In only 1 patient was the diagnosis established without surgery. Immunophenotyping in 10 patients showed 9 B-cell tumors and 1 T-cell tumor. Twelve patients underwent resection. Seven received chemotherapy immediately after the diagnosis was made. Only 3 patients have survived more than 3 years, with the longest survival being 68 months. CONCLUSIONS: Non-Hodgkin's lymphoma of the liver and bile duct must be considered in the differential diagnosis of patients with obstructive jaundice. If the correct diagnosis is made before surgery, current protocols of chemotherapy may be the primary modality of therapy. Surgical resection should be reserved to address complications of biliary obstruction or the failure of chemotherapy to eradicate localized disease.     

Ki-67抗原与乳腺癌的相关性研究

目的探讨Ki-67抗原在乳腺癌组织中的表达,并评价其表达与乳腺癌生物学行为及判断乳腺癌预后的关系。方法检索近年来有关Ki-67与乳腺癌的相关性研究的文献并做综述。结果Ki-67在乳腺癌组织中的表达水平显著高于癌旁组织及正常乳腺组织,且Ki-67表达阳性率与乳腺癌病理分级、临床分期呈正相关,而Ki-67表达与乳腺癌腋窝淋巴结转移的相关性研究结果不尽一致。结论Ki-67抗原是与细胞增殖周期相关的细胞核抗原,其表达随细胞周期的变化而变化,是检测细胞增殖活性较为可靠的标志物,其可能成为判断肿瘤恶性程度及评估预后的重要指标;Ki-67表达水平的检测在乳腺肿瘤的早期诊断、指导新辅助化疗、评估预后等方面有重要意义。     

进展期胃癌术中组织间注射靶向化疗对转移淋巴结Ki-67表达及细胞凋亡的影响

目的：了解进展期胃癌术中组织间注射靶向化疗（IICT）对转移淋巴结Ki-67表达和细胞凋亡的影响。方法：将满足要求的28例进展期胃癌病例随机分成治疗组和对照组。治疗组先于肿瘤组织及周围注射亚甲蓝和丝裂霉素的混合液后再手术,对照组直接手术。观察两组病例转移淋巴结的肿瘤坏死变性有效性、Ki-67表达和细胞凋亡情况。结果：治疗组转移淋巴结的肿瘤细胞变性坏死有效率高于对照组,差异有统计学意义（P〈0.05）;治疗组治疗后转移淋巴结Ki-67表达阳性率低于治疗前,肿瘤细胞凋亡指数高于治疗前,差异均有统计学意义（P〈0.05）;治疗组治疗后转移淋巴结的Ki-67表达低于对照组,肿瘤细胞凋亡指数高于对照组,差异有统计学意义（P〈0.05）.结论：IICT能够抑制胃癌转移淋巴结内肿瘤细胞增殖,促进肿瘤细胞凋亡,对防止医源性扩散、微转移、微残留和术后复发、转移可能有一定作用。     

Preoperative diagnostic value of single-balloon enteroscopy for successful surgical treatment of three independent-origin gastrointestinal malignant tumors: report of a case

A 67-year-old woman with bloody stools underwent esophagogastroduodenoscopy and colonoscopy, which revealed the presence of a submucosal tumor in the stomach and an adenocarcinoma in the ascending colon. Preoperative screening disclosed an additional 10-cm tumor in the abdomen between the gastric and colonic lesions. Single-balloon enteroscopy was therefore performed. A nonstenotic, circumferential, bleeding ulcerative lesion was found in the jejunum, and the biopsy revealed malignant lymphoma (ML). A partial resection of the small intestine, ascending colectomy, and wedge resection of the stomach were performed, then systemic chemotherapy for ML was started 2 weeks after surgery. Triple gastrointestinal malignant tumors with different histologies are extremely rare, and have not been previously reported. Single-balloon enteroscopy in this case led to a definite diagnosis by biopsy, thus allowing the patient to receive chemotherapy as soon as possible after surgery.     

Application of the monoclonal antibody Ki-67 on prostate biopsies to assess the fraction of human prostatic carcinoma.

The feasibility of using the monoclonal antibody Ki-67 as a proliferation marker in human prostatic carcinoma was studied on aspiration and core biopsy specimens obtained from 50 patients suspected of having prostate cancer. In 32 prostatic adenocarcinomas the Ki-67 index varied from 0.3 to 13.3% (mean 4.3) in cytological smears and from 0.8 to 17.8% (mean 5.1) in frozen sections from histological core biopsies. No significant correlation between the percentage of cells positive for Ki-67 and the histological tumor differentiation could be established. In 18 patients with benign prostatic hyperplasia the Ki-67 index varied from 0 to 3.0% (mean 1.2) and from 0 to 3.8% (mean 1.4) in cytological and histological material, respectively. The differences in the observed Ki-67 index between benign and malignant prostatic tissues are of statistical (p less than 0.001) and of clinical significance. Nine patients who underwent endocrine treatment or radiotherapy entered a followup protocol in which the Ki-67 staining procedure was applied to periodically obtained cytological aspiration biopsies. During month 1 after the start of therapy a statistically significant (p less than 0.05) decrease in the Ki-67 index to 58% of the initial values was found, while at 2 and 3 months the proliferative fraction showed a further decrease to 27 and 7%, respectively. As a marker, the monoclonal antibody Ki-67 was shown to provide a reliable method to estimate the proliferative cell fraction of human prostate cancer.