Immunohistochemical study of p53 and Ki-67 antigen expression in bladder carcinoma]

We examined the relationship between the expression of mutant p53 and Ki-67 antigens in urinary bladder transitional cell carcinoma and the pathological and clinical findings. Tissues were obtained from 28 patients with bladder carcinoma who underwent total or partial cystectomy. An ABC immunostaining method and two primary antibodies (DO-7 and MIB-1 antibodies) were used. The percentages of p53 and Ki-67 antigen-positive cells to the total number of cells were regarded as the p53 and Ki-67 labeling indices (LI) respectively. There were no statistically significant correlations between p53 LI and the histological grade or stage, although p53 LI increased slightly in the high grade and high stage group. There was a statistically significant correlation between Ki-67 LI and the histological grade and stage (p < 0.05). The correlation between p53 LI and Ki-67 LI was linear. Some cases had a p53 LI below the mean even though the Ki-67 LI was higher. The clinical course was characteristic of superficial bladder carcinoma initially, but progressed to invasive bladder carcinoma over the next several years. These results suggest that even cases initially diagnosed as superficial bladder carcinoma with a low p53 LI may progress to invasive bladder carcinoma in subsequent years. Therefore, it is important that the patient be followed-up.     

Regional lymphadenectomy for renal pelvic and ureteral cancers

Thirty-four patients with renal pelvic and ureteral cancers received regional lymphadenectomy since 1980. The patients consisted of 21 with renal pelvic cancers, 10 with ureteral and 3 with renal pelvic and ipsilateral ureteral. Fifteen patients (44.1%) had metastatic nodes: 13 with renal hilar or para-aortic metastases and 2 with pelvic nodal involvements only. Thirteen of these 15 patients with nodal metastasis had high grade tumors and 14 had high stage tumors. The 5-year survival rate of these 15 patients was 26.3% which was considerably poor when compared with 19 patients without metastasis. Twenty patients with high grade and high stage tumors who received respective operations with regional lymphadenectomy had significantly better prognosis compared with the historical control group (15 patients, from 1961 to 1979). Additional regional lymphadenectomy for renal pelvic and ureteral cancers appears to be a valuable operation for improving prognosis.     

Immunohistochemical study of bcl-2, p53 and Ki-67 expressions in collecting duct carcinoma of the kidney. Five cases and review of the literature on bcl-2, p53 and Ki-67 expressions in renal cell carcinoma and transitional cell carcinoma

OBJECTIVES: This study was designed to examine the expressions of bcl-2, p53 and Ki-67 antigen in collecting duct carcinoma (CDC) of the kidney by an immunohistochemical method. METHODS: The diagnosis of CDC was based on the criteria proposed by Srigley and Eble. The clinical courses of 5 CDC cases examined in this study suggested that 3 cases were low grade and 2 cases high grade. The expressions of bcl-2, p53 and Ki-67 antigen were evaluated in paraffin-embedded surgical specimens using anti-bcl-2 and anti-p53 antibodies and Ki-67 antigen, respectively. RESULTS: The expression of bcl-2 was recognized in 3 of 5 cases (60%), p53 expression also in 3 of 5 cases (60%). The Ki-67 labeling index was 7.46 +/- 7.40 (mean +/- SD). CONCLUSIONS: It was suggested that there were two clinical types in CDC; the expression of bcl-2 did not correlate with the CDC patients' clinical courses and the cellular proliferation, and p53 expression was recognized in the CDC patients with highly cellular proliferation.     

Clinical studies on renal pelvic and ureteral tumors

Clinical studies were performed on 35 patients with renal pelvic and/or ureteral cancer treated at Kitano Hospital between 1988 and 1997. They consisted of 17 renal pelvic cancers, 17 ureteral cancers and 1 renal pelvic and ureteral cancer. Twenty-nine patients were males and six were females, and their age ranged from 41 to 82 years old (average: 62.2). Histologically, 34 were transitional cell carcinoma and 1 was adenocarcinoma. Pathological stage of the tumor was pTa in 34.3%, pT1 in 14.3%, pT2 in 11.4%, pT3 in 37.1%, and pT4 in 2.9%, and grade of the tumor G1 in 11.8%, G2 in 58.8% and G3 in 29.4%. Eighteen patients (51%) had or developed bladder cancer, which preceded the diagnosis of cancer of upper urinary tract in 2 cases, coexisted in 4 cases and developed subsequently in 12 cases. The overall cause-specific survival rate was 91.3% at 1 year, 83.8% at 3 years and 79.4% at 5 years. Tumor stage, grade, lymph node metastasis and vascular invasion had impact on survival.     

Clinical studies on renal pelvic and ureteral tumors

PURPOSE: We reviewed 77 patients of renal pelvic and ureteral tumor treated at Osaka Police Hospital between 1990 and 2003. METHODS: The patients consisted of 55 males and 22 females. The median age was 69 years, ranging from 42 to 91 years. Median follow-up period was 42 months. RESULTS & CONCLUSIONS: The overall 3, 5 and 10-year cause-specific survival rates were 87.9, 75.3%, 75.3%, respectively. Univariate analysis indicated age, tumor location, number, and shape, stage, grade, infiltrating pattern, lymphatic and venous involvement to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed lymphatic involvement and tumor number to be independent prognosticators for cause-specific survival.     

p53 immunoreactivity correlates with Ki-67 and bcl-2 expression in renal cell carcinoma

This study assessed the relation of proliferation, inhibition of apoptosis, and the p53 tumor suppressor protein expression in clear renal cell carcinoma (RCC). Archival pathological specimens from 43 patients treated for RCC were obtained. Median follow-up for the patients was 52 months (range 2.5 months to 178 months). Immunostaining of paraffin tissue sections was carried out for four different markers: a) Ki-67, a marker for cellular proliferation; b) p53/DO7, c) p53/pAb240, antibodies for the p53 protein; and d) bcl-2, a marker for inhibition of apoptosis (programmed cell death). One thousand cells were counted per slide at 400x magnification. Staining of >/=10% of cells was considered positive and <10% negative. Fisher exact contingency tables were used for correlation between markers, tumor grade and stage. A significant correlation was found between Ki-67 and p53 immunoreactivity samples, P=0.0001. Interestingly, a significant association was found if Ki-67 and bcl-2 scores were combined and correlated with p53, P=0.009. Results showed no correlation between any of the immunohistochemical markers and grade or stage. In addition, Kaplan-Meier survival curves demonstrated no significant difference between patients' tumors that was scored immunoreactive negative vs. positive for Ki-67, p53, or bcl-2. This study indicates that p53 expression correlates with proliferation, and inhibition of programmed cell death in RCC.     

膀胱移行细胞癌中Survivin与Ki-67、p53的表达及临床意义

目的 探讨膀胱移行细胞癌中Survivin、p53及Ki-67的表达与膀胱移行细胞癌临床病理特征的关系及其临床意义. 方法 用免疫组织化学方法 检测88例膀胱移行细胞癌与10例正常膀胱黏膜组织中Survivin、p53及Ki-67的表达,并用RT-PCR方法 验证其中30例膀胱移行细胞癌和10例正常膀胱黏膜组织中Survivin的表达. 结果 免疫组织化学方法 显示在膀胱移行细胞癌中Survivin、p53阳性表达率分别为63.6%(56/88)和45.5%(40/88),正常膀胱黏膜组织中均无表达,差异有统计学意义(P<0.01),且Survivin的表达与膀胱癌的临床分期密切相关(P<0.05).膀胱癌组织中Ki-67增殖指数(PI)为20.4士10.7,正常膀胱黏膜组织中为0.RT-PCR方法 显示在30例膀胱移行细胞癌中Survivin阳性表达率为100%,而正常膀胱黏膜组织中均无表达.结论 Survivin与膀胱癌的恶性程度有关,与p53及Ki-67共同参与了膀胱移行细胞癌的发生、发展及进程.     

p53 and Ki-67 expression as prognostic factors in cystosarcoma phyllodes

We have reviewed the histopathological, clinical outcome and immunohistochemical status in 21 women with cystosarcoma phyllodes (CSP) tumors of the breast. We assessed 12 tumors as histopathologically benign and 9 tumors as malignant. The median patient ages in benign and malignant CSP tumors were 39.6 and 45.4 years of age, respectively. The stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour, and heterologous stromal elements were significant features of the malignant CSP tumors. Benign CSP tumors were predominantly of fibroadenomatous architecture with cellular stroma (mild or moderate) and some distortion and elongation of glandular elements. Five malignant CSP tumors were stained positively with p53, and 6 malignant CSP tumors were stained immunohistochemically with Ki-67. All benign CSP tumors were negatively stained for p53 and Ki-67. The patients with benign CSP tumors were treated with local excision ( n = 11) and with subcutaneous mastectomy ( n = 1). Malignant CSP tumors were treated with wide local excision ( n = 1), partial mastectomy ( n = 1), simple mastectomy ( n = 2), and modified radical mastectomy ( n = 5). Two patients with a high mitotic rate and high values of p53 and Ki-67 received additional radiotherapy and chemotherapy. One case had liver metastasis. This tumor had high mitotic figures, stromal overgrowth, severe stromal cellularity, and 20% Ki-67 and mild p53 positivity. We suggest that p53 and Ki-67 can play an important role in predicting prognosis and yielding additional therapy besides conventional prognostic factors in the treatment of the CSP patients.     

Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia

Anal intraepithelial neoplasia (AIN) is a human papilloma virus related lesion. It has been shown that infection with high-risk human papilloma virus results in up-regulation of p16 and increased cellular proliferation. The objective of this study is to correlate p16 expression and cellular proliferation measured by Ki-67 staining with the degree of dysplasia in the anal canal and to determine the efficacy of these markers in diagnosing high-grade AIN. Seventy-five anal specimens from 55 patients (37 men; 18 women; mean age: 48 y; median: 44 y; range 25 to 96 y) were studied including 35 normal/reactive lesions, 23 low-grade AIN (AIN I and condyloma), and 17 high-grade AIN (AIN II and III). Immunostaining for p16 and Ki-67 was performed. Expression of p16 in AIN correlated with that of Ki-67 (P<0.001). High-grade AIN often demonstrated p16 staining in more than one-third of the thickness of the epithelium in a diffuse/continuous fashion. p16 expression in low-grade AIN was often restricted to the lower 1/3 of the epithelium and/or was focal and discontinuous. The expression of both p16 and Ki-67 correlated with the degree of dysplasia (P<0.01). When positive p16 staining was defined as the presence of diffuse/continuous staining in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of p16 as a marker for diagnosing high-grade AIN were 76%, 86%, and 84%, respectively. When positive Ki-67 staining was defined as the presence of nuclear staining in more than 25% of the cells in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of Ki-67 as a marker for diagnosing high-grade AIN were 71%, 84%, and 83% respectively. Both p16 and Ki-67 are reliable markers for diagnosing high-grade AIN.     

Immunohistochemical study of p53 and Ki-67 overexpression in grade 3 superficial bladder tumor in relationship to tumor recurrence and prognosis]

PURPOSE: The major drawback of the current treatment for superficial bladder tumor is the high rate of recurrence. Especially, the tumor with grade 3 component has a tendency to recur and progress in stage. However, we have difficulty in predicting tumor recurrence and stage progression accurately by conventional clinicopathological factors. We evaluated the efficacy of p53 and Ki-67 overexpression as a predictor of recurrence or prognosis in patients with superficial bladder tumor of grade 3. MATERIALS AND METHODS: Samples were obtained from 41 patients with superficial transitional cell carcinoma of the bladder of grade 3 who were treated by transurethral resection (TUR). The immunohistochemical study was performed using the antibodies against the p53 protein and Ki-67 antigen on formalin-fixed, paraffinembedded tissue specimens from initial tumors. We evaluated the correlation between these results and several clinicopathological factors. RESULTS: The p53 index and the Ki-67 index in pTa, pT1a and pT1b tumors were 26.4 +/- 30.1%, 28.6 +/- 30.0%, and 34.6 +/- 32.6% (p53) and 20.5 +/- 22.5%, 20.0 +/- 29.3%, and 29.2 +/- 28.4% (Ki-67). There was no significant difference between the each index and tumor stage. Eighteen cases (43.9%) had intravesical recurrence. The p53 index of the initial tumor from the tumor free cases (n = 23), recurrent cases without stage progression (n = 12), and stage progression cases (n = 6) were 19.7 +/- 28.2%, 42.0 +/- 28.7%, and 42.5 +/- 32.0%. Between the recurrence-free cases and the recurrent cases without progression, the p53 index of the initial tumor had statistical significance (p < 0.05). The Ki-67 index was shown to be the same pattern as the p53 index, but there was not statistical significance. Four of patients with stage progression had tumor progression within six months. Three of the patients with tumors with stage progression died of the cancer. In multivariate analysis, tumor multiplicity (p = 0.01), BCG intravesical instillation (p = 0.04), p53 index (p = 0.01) and Ki-67 index (p = 0.02) were the positive risk factors for tumor recurrence, but only the p53 index was the positive risk factor for prognosis fo the patients (p = 0.03). CONCLUSION: These results suggest that the immunohistochemical study of p53 overexpression is a useful predictor for tumor recurrence and prognosis in patients with superficial bladder tumor with grade 3.     

p53、p21、Ki-67和VEGF与膀胱癌分级、分期以及预后的关系

目的：探讨p53、p21、Ki-67和VEGF的表达与膀胱癌的病理分级、分期以及预后足否相关。方法：应用免疫组织化学染色的方法,对40例手术证实的膀胱移行细胞癌患者的病理切片进行p53、p2l、Ki-67和VEGF的化学染色。将免疫组化结果与病理分级、分期以及预后情况进行分析。结果：在40个肿榴标本中．p53、p21、Ki-67和VEGF的表达有改变的分别有31个（77.5％）．22个（55.0％）．16个（40.0％）．17个（42.5％）：其中至少1个标记物表达异常35例（87.5％）．而4个标记物均表达异常者有7例（17.5％）。患者平均随访51个月。除了Ki-67、VEGF与病理分级以及Ki-67与分期之间无统计学意义外．4个标记物多少都与膀胱癌的病理分级、分期相关。p53（＋）／p21（-）以及4个标记物同时异常是与疾病相关死亡率有关的独立因素（P＜0.05,P＜0.01）。而Ki-67、VEGF均不是膀胱癌相关死亡率的独立因素（P〉0．05）。越多标记物表达异常,则膀胱癌的死亡率增加。结论：p53、p21、Ki-67和VEGF多少都与膀胱癌的病理分级、分期相关。联合检测p53、p21、Ki-67和VEGF可以更加准确地预测膀胱癌的预后。     

A clinical study of patients undergoing curative surgery for renal pelvic and ureteral cancers

We retrospectively studied 30 patients who underwent curative surgery for renal pelvic and/or ureteral cancer between August 1987 and August 1998. Their clinicopathological features were classified by the criteria of the Japanese Urological Association. The 1-, 3-, and 5-year cause-specific survival rates were, respectively, 100, 95.5, and 85.1%, while the disease-free rates were 100, 78.9, and 78.9% by the Kaplan-Meier method. Prognostic factors were evaluated by the log-rank test. The significant prognostic factors were pT3 and pV1 for cause-specific survival (p = 0.0277, p = 0.0025), while pT2 (or higher), grade 3, and pV1 were significant for disease-free survival (p = 0.0271, p = 0.0327, and p = 0.0002). Nine patients who received adjuvant chemotherapy are alive, but 3 patients have relapsed. Chemotherapy did not have a significant effect on the cause-specific survival or disease-free survival.     

MCM2p、p16INK4A和Ki-67在肝癌组织中的表达

目的 探讨MCM2p在肝癌中的表达及其与肿瘤细胞增殖活性的关系.方法 采用免疫组织化学法检测MCM2p、p16INK4A和Ki-67在肝细胞肝癌及其相应的癌旁正常组织中的表达.结果 肝癌组织MCM2p和Ki-67的表达显著高于癌旁肝组织(P《0.01),而p16INK4A表达显著低于癌旁肝组织(P《0.01).MCM2p的表达和Ki-67的表达状况关系密切,呈正相关,而与p16INK4A表达呈负相关.结论 MCM2p和Ki-67在肝癌组织中呈高表达,并与肝癌的发生发展及肿瘤的增殖活性有关.     

TK1、Ki-67、p53在乳腺癌组织中的表达与及其预后的关系

目的：探讨TK1、Ki-67、p53在乳腺癌组织中的表达及其与预后的关系。 方法：2009年3月—2013年5月收治的60例乳腺癌患者,均接受乳腺癌根治术并留取组织标本,用免疫组化法检测乳腺癌组织及其癌旁组织中TK1、Ki-67和p53的表达;根据随访资料分析TK1、Ki-67和p53的表达与患者预后的关系。 结果：乳腺癌组织中TK1、Ki-67、p53阳性率均明显高于癌旁组织（均P<0.05）;TK1、Ki-67、 p53的表达强度明显影响患者的5年生存率,均表现为表达强度越高患者的生存率越低（均P<0.05）;TK1、Ki-67和p53表达的阳性率在术后5年内出现复发或转移的患者中均明显高于无复发或转移的患者（均P<0.05）。 结论：在乳腺癌组织中TK1、Ki-67和p53表达增强,且其表达强度与乳腺癌的不良预后密切相关。     

膀胱尿路上皮癌中S-100、p53和Ki-67的表达及临床意义

目的：研究膀胱尿路上皮癌中S-100、p53和Ki-67的表达及临床意义。方法：采用免疫组织化学SP法检测60例膀胱尿路上皮癌及15例正常膀胱组织中S-i00蛋白、p53和Ki-67的表达情况。结果：S-100、p53和Ki-67在膀胱尿路上皮癌中的表达均高于其在正常膀胱黏膜中的表达。膀胱尿路上皮癌组织中S-100阳性表达随着肿瘤病理分级、临床分期的升高而降低;p53与Ki-67阳性表达率随肿瘤病理分级、临床分期的升高而升高;S-100低表达和p53与Ki-67高表达与术后复发密切相关。结论：联合检测S-100、p53及Ki-67的表达可以作为判断膀胱尿路上皮癌生物学行为及预后的重要指标。     

Prognostic value of p53, proliferating cell nuclear antigen, and Ki-67 expression in undifferentiated nasopharyngeal carcinomas

In this study the prognostic importance of p53, proliferating cell nuclear antigen (PCNA), and Ki-67 expression was analyzed along with the clinical parameters in 35 consecutive patients with undifferentiated nasopharyngeal carcinomas. Immunohistochemistry was used to detect p53, PCNA, and Ki-67 staining. Among the clinical findings, stage IV disease (P = 0.01), cranial nerve paralysis (P = 0.02), and lymph node metastasis (P = 0.06) were associated with shorter survival. The p53 positivity correlated with the presence of lymph nodes, but it was not a significant factor to predict the outcome. PCNA expression was not found to be a prognostic indicator. On the other hand, the proliferative value of Ki-67 staining was suggestive of prognosis. A proliferation index of Ki-67 less than 10% indicated longer survival (P = 0.03). There was no correlation between Ki-67 staining and PCNA index. As a result, the prognostic value of Ki-67 may alert the physician to more aggressive and adjuvant treatment modalities.     

Clinical observation on renal pelvic and ureteral tumors

During the 18 years from October, 1971 to September, 1989, 40 patients with renal pelvic and ureteral tumors were treated at our Department of Urology. Thirty were male and 10 female, and were between 44 and 83 years old with a mean age of 65.5 years. Histopathologically, there were 38 transitional cell carcinomas and 2 squamous cell carcinomas. There was a positive correlation between grade and stage of tumor. Among the patients with transitional cell carcinoma, the five-year survival rate was 54.4% for all the patients, 57.1% for patients with renal pelvic tumors and 48.4% for those with ureteral tumors respectively, as measured by the Kaplan-Meier's method. Stage and intravascular invasion of the tumor were the most influential factors for prognosis. There was no evidence in this series to show the usefulness of postoperative adjuvant chemotherapy, such as bladder instillation or peroral administration of various anti-tumor drugs, as a prophylactic use for recurrence of the bladder tumor in low stage cases.