Can Ki-67 predict recurrence of NO squamous cell carcinoma of the tongue?

OBJECTIVES: Ki-67 is a molecular marker of cellular proliferation that predicts prognosis of some head and neck tumors. Studies of Ki-67 in oropharyngeal cancer have yielded conflicting findings. This study was designed to test Ki-67 as a marker for poor prognosis in N0 tongue squamous cell carcinoma. METHODS: We examined 29 cases in a retrospective cohort to test the hypothesis that a high rate of tumor cell proliferation (high levels of Ki-67 staining) at the invasive edge of N0 squamous cell carcinoma of the tongue correlates with increased risk of recurrence. RESULTS: There were 14 cases of recurrence. The average age of the patients with recurrence was 58 years. The average time to recurrence was 13.1 months. A 0% to 33% uptake of Ki-67 at the tumor's leading edge was associated with a 6-times-greater risk of recurrence. The mean length of survival for the group with 0% to 33% uptake was 21 months; for the group with > 33% uptake, it was 33 months. Overall uptake of Ki-67 and histologic grade did not correlate with risk of recurrence. CONCLUSIONS: In this sample, low rates of Ki-67 staining at the invasive edge of the tumor predicted a risk of recurrence. These results need to be confirmed before Ki-67 can be used for predicting recurrence of tongue squamous cell carcinoma.     

Ki-67 As a Prognostic Marker in Adenoid Cystic Carcinoma Assessed With the Monoclonal Antibody MIB1 in Paraffin Sections

The monoclonal antibody MIB1 recognizing the Ki-67 antigen in formalin-fixed, paraffin-embedded tissue was used to study the proliferative activity in 44 adenoid cystic carcinomas of the salivary glands. The antigen expression was compared with clinical factors, histopathological grading, and prognosis. The Ki-67 value was significantly higher in tumors from patients suffering from treatment failure than in nonfailures (P < 0.001). The Ki-67 expression was also higher in tumors exhibiting areas more than 30% of the solid growth pattern and higher in sinonasal tumors than in other locations. By Cox regression analysis, Ki-67 more than 4% was the strongest prognostic indicator (P <0.005). Clinical stage and violation of surgical margins were also found to be independent significant prognostic indicators. We conclude that Ki-67 expression estimated by the use of MIB1 is a powerful tool for predicting the short-term prognosis for patients with adenoid cystic carcinoma.     

Pleomorphic adenoma of the submandibular gland: clinicopathological and immunohistochemical features of 60 cases in Brazil

The submandibular gland is involved in only 5% to 10% of the salivary gland tumors, and pleomorphic adenoma (PA) is the most common tumor affecting it. This study describes the clinicopathological features and immunohistochemical expression of Ki-67 and p53 in 60 cases of submandibular salivary gland PAs. Most of the patients were in the third and fifth decades of life and 37 (62%) of them were women. Tumor sizes varied from 1 to 10 cm and the mean time between symptom onset and treatment was 52 months. Only 1 patient experienced local recurrence, 3 years after treatment. Histologically, most tumors consisted chiefly in a chondromyxoid stroma. Stroma-rich PAs were larger than stroma-poor ones (P<.02). All PAs were found negative for Ki-67 and p53. These results show that PAs of the submandibular gland are histologically similar to PAs of other salivary glands, and that they have a low proliferative rate and a good prognosis.     

Ki-67 and p53 in T2 laryngeal cancer

Objective: To study the relationship between the proliferative capacity, represented by the immunohistochemical labeling index (LI) of proliferation marker Ki-67, and the p53 status, as in theory an intact p53 cell cycle checkpoint system should result in a lower proliferative capacity. Study Design: From a group of 128 patients with a T2 laryngeal carcinoma, presented from 1989 to 1993 at the University Hospital Utrecht, 20 patients with recurrent disease and 16 patients without recurrent disease were randomly selected. All patients received primary irradiation. Methods: Denaturing gradient gel electrophoresis and immunohistochemistry determined the p53 status. MIB-1 staining was used to determine the Ki-67 LI. Results: In 36% of specimens we found a p53 mutation with overexpression (LI, 31%). In 8% a p53 mutation without p53 overexpression was found (LI, 18%). Forty-two percent showed no mutation but, nevertheless, overexpression (LI, 35%). Neither mutation nor overexpression was found in 14% (LI, 38%). No correlation exists between p53 status and proliferative capacity of tumors (analysis of variance [ANOVA]; P = .104). The proliferation rate as established with Ki-67 LI positively correlates with response to radiotherapy (P = .006). Conclusions: 1. Overexpression of wild-type p53 protein does not result in cell cycle arrest measurable by a lower Ki-67 LI in comparison with cases overexpressing mutant type p53 protein. 2. A high Ki-67 LI correlates with a favorable response to radiotherapy. Laryngoscope, 108:1548–1552, 1998     

MCM2和Ki-67及Rb蛋白在喉鳞状细胞癌中的表达及意义

目的:探讨微染色体维持蛋白2(MCM2)、增殖细胞核抗原(Ki-67)和视网膜母细胞瘤易感基因(Rb)与人喉鳞状细胞癌(LSCC)发生、发展和预后的关系。方法:应用免疫组织化学ElivisionTMplus二步法检测60例LSCC、10例喉癌前病变、10例声带息肉及10例癌周正常喉组织中MCM2与Rb蛋白的表达,同时检测Ki-67蛋白在LSCC及癌周正常喉组织中的表达并结合临床资料进行分析。结果:①LSCC中MCM2蛋白的表达水平明显高于喉癌前病变及癌周正常喉组织(均P<0.05),且与喉癌病理分级、临床分期及淋巴结转移有关(均P<0.05);LSCC中Rb蛋白表达水平明显低于癌前病变及癌周正常喉组织(均P<0.05);LSCC组织中MCM2与Rb蛋白的表达呈负相关(r=-0.542,P<0.05);②LSCC组织中Ki-67蛋白的阳性表达率(76.67%)明显高于癌周正常喉组织(30.00%),差异有统计学意义(P<0.01),MCM2、Ki-67蛋白在LSCC中的表达呈正相关(r=0.596,P<0.01),MCM2与Ki-67蛋白的标记指数在生存时间≥3年组和<3年组差异有统计学意义(P<0.05)。结论:MCM2蛋白的表达升高和Rb蛋白的表达下降与LSCC的发生、发展有关,检测MCM2有助于判定LSCC的恶性程度及预后。     

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.     

Benign and malignant oncocytoma of the salivary glands with an immunohistochemical evaluation of Ki-67

We present two cases of benign oncocytoma derived from the parotid gland and minor salivary gland and one case of malignant oncocytoma from the parotid gland. The proliferative activity of the tumor cells was evaluated immunohistochemically for Ki-67. The average frequency of Ki-67-positive cells was 3.3% in the benign oncocytomas and 6.5% in the malignant oncocytoma. The higher frequency of Ki-67-positive cells in the malignant oncocytoma might reflect active cell proliferation. Ki-67 immunostaining may be useful in distinguishing a benign oncocytoma from a malignant oncocytoma.     

垂体腺瘤侵袭性与质地的相关性研究

目的探讨垂体腺瘤侵袭性与质地的关系。方法收集2008年1月～2010年1月经病理证实的垂体腺瘤患者76例,其中功能腺瘤44例,无功能腺瘤32例;根据术前影像学检查分为侵袭组32例,非侵袭组44例;根据术中判断分为质地软组54例和质地硬组22例。应用免疫组化SP法检测76例垂体腺瘤标本中Ki-67和基质金属蛋白酶2(MMP2)的表达水平。统计分析垂体腺瘤侵袭性与Ki-67和MMP2表达的关系及垂体腺瘤侵袭性与质地的关系。结果侵袭组Ki-67和MMP2的表达水平分别为7.573±3.991和18.623±9.689,显著高于非侵袭组2.811±2.095和6.871±7.230(t1=6.161,t2=5.788,P<0.01),Ki-67与MMP2表达呈正相关(r=0.476,P<0.01)。垂体腺瘤的侵袭性与质地无明显相关性(P=0.056)。结论 Ki-67和MMP2可作为诊断垂体腺瘤侵袭性的分子标记物,检测Ki-67和MMP2表达水平可指导临床评价垂体腺瘤侵袭性及制定个体化治疗方案,而术前仅依靠垂体腺瘤的侵袭性影像学特征并不能判断其质地。     

Immunohistochemical markers of cell proliferation in laryngeal carcinoma

Although several clinicopathological factors may contribute to the prognosis of laryngeal carcinoma, these factors are still uncertain because the carcinogenesis process and malignant behavior are not well known. Immunohistochemical methods using two important markers, PCNA and Ki67 antigen, were used to assess proliferative activity in malignant laryngeal lesions. We studied the correlation between expression of these markers and clinical factors in 72 patients with carcinoma of the larynx: age, sex, occupation, smoking, alcohol consumption, marital status, etc. We also analyzed other known biological and histopathological prognostic factors (tumor stage, histological grade, lymph node metastases, and local invasion). PCNA and Ki-67 expression differed significantly in relation to histological grade and lymph node involvement. No associations were seen between the expression of PCNA and Ki-67 antigens and other study parameters.     

Expression patterns of Ki-67 and telomerase activity in middle ear cholesteatoma.

BACKGROUND: Keratinocytes in cholesteatoma demonstrate uncoordinated hyperproliferation, migration, and invasion properties. There is a controversy regarding the impact of Ki-67 and telomerase activities on cellular proliferation in cholesteatoma. We studied expression of Ki-67 protein and telomerase activity in cholesteatoma and its relationship with clinical findings. METHODS: The expression level of Ki-67 protein was examined by immunohistochemical analysis of 51 cholesteatomas and 6 skin tissues obtained from patients during ear surgery. Telomerase activity was determined in 23 samples of cholesteatomas and 6 skin samples by polymerase chain reaction-based telomeric-repeat amplification protocol assay. RESULTS: The presence of Ki-67 protein was observed in 21 (41.2%) of 51 samples of acquired cholesteatoma. The average Ki-67 labeling index in the cholesteatoma group was 28.9 +/- 9.2 and was higher than that in the skin group (18.2 +/- 6.1). Telomerase activity was detected in 2 (8.7%) of 23 samples of cholesteatoma (21 of them were Ki-67 staining positive and 2, negative) and in 3 (50%) of 6 of control skin samples (p < 0.05). CONCLUSION: This study showed increased expression of Ki-67 in cholesteatoma, whereas there was no significant difference in rate of Ki-67 positive staining between skin and cholesteatoma (p = 0.066). Telomerase activation is a rare event in cholesteatoma. We assume that the absence of telomerase may lead to generation dysfunctional telomeres what in turn may impair the proliferative capacity of cholesteatoma.     

成人喉乳头状瘤复发的相关因素研究

目的 :研究成人喉乳头状瘤复发的相关因素。方法 :收集成人喉乳头状瘤复发标本 5 0例 ,另选 10例炎症病变黏膜组织作为对照。应用SP法检测石蜡标本中耐药基因胎盘型谷胱甘肽 S 转移酶 (GST π)、DNA拓朴酶Ⅱ (TopoⅡ )、P 糖蛋白 (Pgp)和Ki 6 7、血管内皮生长因子 (VEGF)的表达 ,并用形态计量方法检测肿瘤内微血管密度 (MVD) ,对所得的各项指标进行统计学分析。结果 :①耐药基因Pgp、GST π和TopoⅡ的表达与年龄、性别、肿瘤大小及肿瘤复发无显著相关 (P >0 .0 5 )。②Ki 6 7在复发肿瘤与非复发肿瘤组织之间差异有统计学意义 (P <0 .0 1)。多元回归分析显示该指标是肿瘤复发的独立危险因素之一 ,以 39%为分界点 ,大于 39%者容易复发。③MVD >19(× 2 0 0 )的成人喉乳头状瘤比 <19的成人喉乳头状瘤容易复发。结论 :用Cox 逐步回归模型进行多因素分析 ,筛选出了与成人喉乳头状瘤复发有密切关系的 5个指标 :Ki 6 7阳性率是最重要的复发因子 ,其次为MVD ,而肿瘤耐药因子Pgp、TopoⅡ、GST π无明显意义。     

Ki-67、p53和VEGF在鼻咽癌组织中的表达及临床意义

目的探讨Ki-67、p53和VEGF在鼻咽癌组织中的表达及其临床意义。方法选择2015年1月至2020年7月在我院初诊的鼻咽癌患者90例为观察组,选择同期50例在我院就诊的鼻咽黏膜慢性炎症患者为对照组。通过免疫组化检测两组鼻咽组织中Ki-67、p53和VEGF的表达,并探讨三个免疫组化指标与临床病理特征之间的关系。结果(1)鼻咽癌组织中Ki-67、p53、VEGF阳性表达均明显高于鼻咽部炎症组(P<0.05)。(2)鼻咽癌组织中Ki-67、p53、VEGF阳性表达与患者的性别、年龄等病理因素没有相关性(P>0.05),与病理分型、颈部淋巴结转移以及临床分期具有密切相关性(P<0.05)。(3)Ki-67、p53、VEGF三者在鼻咽癌组织中的表达相互之间均呈正相关(P<0.05)。结论Ki-67、p53和VEGF与鼻咽癌的发生和发展有密切相关性,三者的检测对鼻咽癌的诊断及治疗具有重要的参考价值。     

DNA index,cellular proliferative activity and nucleolar organizer regions in cancers of the larynx

The DNA index, expression of cell-cycle-related proteins — proliferating cell nuclear antigen (PCNA, cyclin) and Ki-67 — and the content of silver-binding nucleolar organizer regions (AgNORs) were evaluated in 30 unselected consecutive primary squamous cell carcinomas of the larynx. Results were compared and subsequently related to histological grading, lymph node status, pT category, and pathological stage. DNA content was non-diploid in 9 cases (30%). Mean AgNOR counts per tumor ranged from 2.52 to 8.76. PCNA and Ki-67 expressions were similar in 10 cases (33%). In the remaining cases, PCNA-positive cells usually outnumbered Ki-67-positive cells. No significant correlation was found among DNA index, PCNA and Ki-67 expressions, and AgNOR counts. Although there was a positive trend when Ki-67 was compared with histological grading, findings were not statistically significant. In contrast, a significant correlation was found between DNA index and lymph node status (P = 0.035), with a higher incidence of neck node metastases in non-diploid tumors. These data suggest that tumor ploidy can be correlated with lymph node spread in laryngeal squamous cell carcinoma and might be used as an additional prognostic factor when planning treatment.     

Flow cytometric analysis of DNA content and Ki-67-positive fractions in the diagnosis of salivary gland tumors

To explore the utility of flow cytometry (FCM) for the diagnosis of histopathology of salivary gland tumors, fresh materials taken at surgery from 23 Warthin’s tumors, 57 pleomorphic adenomas, and 14 malignant tumors were analyzed for DNA ploidy and proliferative cell activities, including S-phase fraction (SPF), G2- plus M-phase fraction (G2M), and Ki-67-positive fraction. To facilitate this study, glands were taken from all major salivary sites and minor glands in the head and neck. DNA aneuploidy was not detected in the benign tumors. Nine of 14 malignant tumors showed DNA aneuploidy. The percentage of SPF or G2M of the malignant tumors was significantly higher than those of the benign tumors. The percentage of Ki-67-positive fraction of pleomorphic adenomas was comparable to that of malignant tumors and was significantly higher than that of Warthin’s tumors. Ki-67 of 20% as a cut-off had a sensitivity of 88%, specificity of 100%, and accuracy of 91% for differentiating pleomorphic adenomas from Warthin’s tumors. In analyzing DNA content and proliferative activities by FCM, we could distinguish among the three major histopathologies of salivary gland tumors. Warthin’s tumors showed low SPF+G2M with low Ki-67, pleomorphic adenomas had low SPF+G2M with high Ki-67, and malignant tumor showed high SPF+G2M with high Ki-67. The high percentage of the Ki-67-positive fraction seen in pleomorphic adenomas may reflect their potential biological aggressiveness manifested as tumor recurrence or malignant transformation. Received: 26 June 1997 / Accepted: 5 November 1997     

Adhesion molecules as prognostic factors in nasopharyngeal carcinoma.

OBJECTIVE/HYPOTHESIS: To identify the significance of molecular markers in determining the risk of recurrence and distant metastases in nasopharyngeal carcinoma. STUDY DESIGN: In this retrospective case study, we evaluated archival nasopharyngeal carcinoma specimens for patterns of expression of E-cadherin, beta-catenin, c-erb-B2, and Ki-67, which have been demonstrated to be important in other tumors. METHODS: Fifty-four cases of nasopharyngeal carcinoma were identified, with a maximum follow-up of 13 years. The histopathological sections were stained using an automated immunohistochemical stainer (NexES, Ventana Medical Systems, Tucson, AZ) for E-cadherin (Zymed Laboratories [San Francisco, CA] and Transduction Laboratories [Lexington, KY] clones), beta-catenin (Zymed), c-erb-B2 (Ventana Medical Systems), and Ki-67 (Novocastra, Burlingame, CA). The numbers of positively staining cells were scored as follows: 0%, 1% to 33%, 34% to 66%, or greater than 67%. RESULTS: E-cadherin (Zymed) stained positively in only one case. The Transduction Laboratories clone demonstrated a spectrum of staining in all cases, from complete to disrupted to no identifiable membranous staining. The staining was consistently absent at the advancing tumor border, regardless of stage. The loss of beta-catenin expression did not correlate with that of E-cadherin or with clinical outcomes. No staining was identified for c-erb-B2. Ki-67 staining was variable and did not correlate with clinical outcomes. CONCLUSIONS: Altered expression or loss of E-cadherin, or both, may result in loss of function, particularly at the infiltrating edge, with resultant loss of cell polarity, cell migration, and eventual metastasis. The interpretation of E-cadherin staining depends on antibody source. In contrast to recent studies, beta-catenin expression is not altered and c-erb-B2 expression not identified, suggesting that these markers are not important in the prognosis of nasopharyngeal carcinoma.     

Evaluation of proliferative activity in human head and neck tumors using the monoclonal antibody Ki-67

The monoclonal antibody Ki-67 is directed against a human nuclear antigen occurring in proliferating cells. As a rule it is absent in quiescent cells. Seven cases of squamous cell carcinomas with different pathohistological features are investigated by immunostaining. The antibody Ki-67 is suitable for use as a marker for proliferative compartments of head and neck tumors. Squamous cell carcinomas show a correlation between Ki-67 labeling index and histological differentiation. In highly differentiated parts of the carcinomas, an additional granular immunostaining in the entire cytoplasm of some squamous epithelial cells was observed.     

Retrospective analysis of Ki-67 antigen expression in paraffin tissue blocks of laryngeal squamous cell carcinoma

The level of Ki-67 antigen expression has been proven to correlate with cellular proliferation. The aim of the study was to show correlation of Ki-67 expression with the clinical stage and its predictive value for the prognosis of laryngeal carcinoma. The study included 48 patients with surgically removed carcinoma of the larynx. Study results pointed to a significant difference in the mean value of Ki-67 reactivity between the study and control group consisting of cadaveric laryngeal tissue free from the disease. Correlation was found between the TNM stage of carcinoma and percentage of Ki-67-labeled cells. A significant correlation was also observed between Ki-67 reactivity at the time of laryngeal surgery and 2-year clinical outcome of the disease. Ki-67 reactivity was significantly higher in the group of patients with disease remission compared with the control group but was significantly lower as compared with the group of patients with poor outcome.     

12例头颈部髓外浆细胞瘤的病理与免疫组化研究

目的 :探讨头颈部髓外浆细胞瘤 ( EMP)的组织学特点、临床行为、免疫球蛋白分泌功能与预后的关系。方法 :对 12例头颈部 EMP患者的手术蜡块进行病理观察与免疫组化检测。结果 :12例中 ,低度恶性 ( 级 ) 3例 ,中度恶性 ( 级 ) 3例 ,高度恶性 ( 级 ) 6例 ;免疫组化显示肿瘤均为单克隆性 ,Ig Gκ、Ig Gλ阳性各 6例。除鼻咽部 2例外 ,均接受手术切除加放疗。 、 、 级 EMP 5年生存率分别为 75 .0 %、6 2 .0 %、37.6 % ;Ig Gκ阳性者6 8.5 % ,Ig Gλ阳性者 37.5 % ,两者有显著性差异 ( P <0 .0 1)。结论 :免疫组化检测对头颈部 EMP鉴别诊断有重要作用 ,手术加放疗为有效的治疗手段 ,组织学分级、免疫球蛋白分泌功能对判断其预后有一定价值     

表皮生长因子受体和C-erbB2及Ki-67在鼻部鳞状细胞癌中的表达及意义

目的:探讨表皮生长因子受体(EGFR)、C-erbB2及Ki-67在鼻部鳞状细胞癌(SCC)中的蛋白表达及其在该病发生、发展中的意义.方法:采用免疫组织化学SP法检测31例鼻腔鼻窦SCC、12例鼻息肉(NP)和17例鼻内翻性乳头状瘤(IP)组织中EGFR、C-erbB2和Ki-67蛋白的表达.结果:EGFR与Ki-67在鼻腔鼻窦SCC中的阳性表达率明显高于IP(P＜0.05,P＜0.01)与NP组织(P＜0.05,P＜0.01),C-erbB2在SCC中的表达明显高于NP组织(P＜0.05),3种蛋白均与SCC组织分级无关.结论:EGFR的过度表达可能是鼻部SCC发病的早期表现,C-erbB2的过度表达可能与鼻部SCC的发展及病理分级有关,Ki-67的免疫组织化学表达特征可作为反映鼻腔鼻窦肿瘤生物学行为的客观指标,但3种生物标志物均不能作为评价SCC病理分级的检测指标.     

Ki-67 immunostaining and prognosis in laryngeal cancer

The expression of the antigen defined by the Ki-67 antibody in paraffin sections from 154 biopsies of laryngeal squamous cell carcinomas was examined. There was a significant difference in Ki-67 expression between the control group and the patients with cancer (P < 0.001). There was no significant difference in the Ki-67 score between the patients with recurrence and the patients with a satisfactory outcome after treatment. There was no significant correlation between the Ki-67 score and the patient's age and sex, T and N stage and site of the tumour. The survival time of patients with a Ki-67 score > 30 was shorter than patients with a Ki-67 score ≤ 30 but the difference did not reach statistical significance (P= 0.055). Multivariate analysis indicated that the only important prognostic factor was the existence of lymph node metastases. We could not confirm the value of Ki-67 as a prognostic factor in laryngeal cancer. Ki-67 score may assist in differentiating malignant from benign laryngeal epithelium.