Bcl-2Ki-67的表达预测恶性淋巴瘤造血干细胞移植后复发的临床研究

目的:研究Bcl-2、Ki-67在恶性淋巴瘤(Malignant lymphoma,ML)组织中的表达以及与自体造血干细胞移植(autologous hematopoietic stem celltransplantation,AHSCT)预后的相关关系.方法:1)采用免疫组织化学(immunohistochemistry,IHC)法检测33例行AHSCT治疗的患者组织切片中Ki-67,Bcl-2的表达.并探讨Ki-67,Bcl-2的表达与预后的相关性.2)生存率统计采用Kaplan-Meier生存曲线,Log-rank检验,多因素分析采用Cox风险回归模型.结果:1)33例AHSCT治疗组,Bcl-2阳性表达组和阴性表达组移植后3年无病生存率分别为35.71%和88.89%(P<0.05);Ki-67阳性表达组和阴性表达组3年无病生存率分别为43.75%和85.71%(P<0.05),提示Bcl-2和Ki-67的表达与AHSCT的预后相关.2)Cox多因素分析显示,Ki-67和Bcl-2是影响ML患者AHSCT后无病生存的相关因素(P=0.043 7).结论:Bcl-2、Ki-67蛋白阳性表达的ML患者,AHSCT后易复发,可作为移植后预后判断的指标之一.Ki-67和Bcl-2是影响ML患者AHSCT无病生存的独立相关因素.     

p27与Ki-67联合检测对乳腺癌的预后意义

 目的　探讨联合检测细胞周期抑制剂p27和核蛋白Ki-67对乳腺癌的预后意义。方法　应用免疫组织化学方法检测手术切除并经术后病理证实的86例乳腺癌患者组织中p27和Ki-67的表达,利用Log-Rank检验行生存分析;COX比例风险模型行单因素及多因素分析。结果　Log-Rank检验显示p27低表达且Ki-67高表达者无瘤生存期明显缩短（χ2＝7.56;P＝0.003）;COX单因素分析提示淋巴结转移（P＝0.008）、肿瘤大小（P＝0.002）、p27低表达（P＝0.001）、Ki-67高表达（P＝0.015）均是影响乳腺癌患者无瘤生存率的因素,多因素分析提示p27低表达与Ki-67高表达同时存在是影响乳腺癌患者无瘤生存率的最显著的预后因子（P＝0.008）。结论　对乳腺癌组织中p27和Ki-67的检测有利于评估乳腺癌患者的预后,p27低表达及Ki-67高表达预示乳癌患者预后差,两者同时检测有助于提高对乳腺癌预后判断的准确性。     

124例三阴性乳腺癌临床病理因素与预后分析

目的:三阴性乳腺癌（triple-negative breast cancer,TNBC）预后差,易复发转移,缺乏有效的治疗手段。本文回顾性分析TNBC及基底细胞型的临床病理因素与预后的关系。方法:纳入江苏省肿瘤医院124例TNBC,Fisher法分析临床病理因素之间的相关性,Kaplan-Meier法分析Ki-67/p53与无进展生存期的相关性,COX回归模型分析无进展生存期的预后因素。结果:TNBC肿块大小与腋窝淋巴结转移相关,Ki-67高表达与腋窝淋巴结转移相关,p53阳性与病理分级相关。TNBC及基底细胞型中,Ki-67高增殖与p53阳性患者具有相对较差的无病生存期（P＜0.05）。临床分期、腋窝淋巴结转移阳性、Ki-67高增殖与p53阳性是TNBC无病生存的独立预后因素。结论:本文证实Ki-67及p53是TNBC生存预后的预测因子,为TNBC延长生存、改善预后提供依据。     

EGFR、p53、Bcl-2表达,Ki-67标记指数与胸腺瘤WHO组织学分型、分期及预后的关系

目的探讨EGFR、p53、Bcl-2表达，Ki-67标记指数（Ki-67Li）与胸腺瘤WHO组织学分型、分期及预后的关系。方法应用免疫组化染色方法检测46例胸腺瘤患者EGFR、p53、Bcl-2的表达和Ki-67标记指数。结果胸腺瘤EGFR、p53、Bcl-2阳性表达率分别为34．8％、56．5％、54．3％，Ki-67标记指数平均值为11．0％。EGFR、p53、Bcl-2蛋白表达与胸腺瘤WH0组织学分型均无明显关系；B2、B3、C型与A、AB、B1型之间Ki-67标记指数表达差异有显著性（P〈0．05）；Bcl-2蛋白表达与胸腺瘤Masaoka分期和预后均无关系（P〉0．05）；EGFR、p53蛋白的过度表达和Ki-67标记指数与胸腺瘤Masaoka分期明显相关（P〈0．05）；Ki-67标记指数与预后有关（P〈0．05）。结论EGFR、p53蛋白的过度表达和Ki-67标记指数与胸腺瘤Masaoka分期明显相关，反应其侵袭性，Ki-67标记指数还与组织学分型相关，并可作为估计胸腺瘤预后的参考指标。     

韦氏环淋巴瘤中bcl-2、p53表达与预后的关系

目的以44例原发于韦氏环的B细胞中度恶性淋巴瘤作为对象，探讨bcl-2、p53阳性表达与预后的关系。方法22例韦氏环B细胞淋巴瘤患者蜡块，采用免疫组化S—P法染色，以细胞核着色计数分为阴性、阳性、强阳性。结果bcl-2阳性率59％，p53阳性表达率45％，bcl-2阳性表达组较其阴性表达组生存率低，有统计学意义，p53阳性表达组与阴性表达组比较其生存率未见统计学差异。结论临床上检测bcl-2蛋白表达可作为判断韦氏环B细胞、中度恶性淋巴瘤预后因子的指标。     

非霍奇金淋巴瘤组织中突变型p53、bcl-2、Ki-67及survivin蛋白表达及临床意义

目的:探讨突变型p53、bcl-2、Ki-67、survivin在非霍奇金淋巴瘤(NHL)组织中的表达及其临床价值.方法:采用组织芯片技术及免疫组化SP法检测142例NHL和18例良性淋巴结病变组织中突变型p53、bcl-2、Ki-67、survivin蛋白的表达.结果:突变型p53、bcl-2、Ki-67、survivin蛋白在NHL中的表达阳性率分别为55.63%(79/142)、51.41%(73/142)、48.59%(69/142)和60.56%(86/142);与对照组相比具有非常显著性差异(P<0.01).在不同性别以及在不同细胞类别NHL中,突变型p53、bcl-2、Ki-67、survivin蛋白表达阳性率基本一致,统计分析无显著性差异(P>0.05);但在低年龄组、临床Ⅲ-Ⅳ期和高度恶性组突变型p53、bcl-2、Ki-67、survivin蛋白表达阳性率明显高于高年龄组、临床Ⅰ-Ⅱ期和低度恶性组,有显著性差异(P<0.05);突变型p53蛋白与Ki-67蛋白呈正相关(r=0.8769),survivin蛋白与bcl-2蛋白表达呈正相关(r=0.8846).结论:突变型p53、bcl-2、Ki-67、survivin蛋白在NHL组织中高表达,与NHL的发生与发展、细胞恶性程度和组织病理学等级密切相关.     

TopoⅡ、p53、Ki-67、c-erbB-2在乳腺癌组织中的表达

目的：检测TopoⅡ、p53、Ki-67、c-erbB-2在乳腺癌组织中的表达,分析其与乳腺癌临床病理特征间的关系。方法：采用免疫组化方法检测66例未经抗肿瘤治疗的原发性乳腺癌组织中Topo II、p53、Ki-67、c-erbB-2的表达情况。结果：乳腺癌组织中TopoⅡ、p53、Ki-67、c-erbB-2阳性表达率分别为57.6%（38/66）、60.6%（40/66）、62.1%（41/66）、51.5%（34/66）,Topo Ⅱ、Ki-67、p53、c-erbB-2表达与患者年龄、肿瘤大小无关（P〉0.05）,TopoⅡ、p53、Ki-67、c-erbB-2与淋巴结转移相关（P〈0.05）,其中p53、Ki-67、c-erbB-2与肿瘤临床分期相关（P〈0.05）。结论：联合检测乳腺癌组织中c-erbB-2、p53、Ki-67可以作为判断乳腺癌患者预后的有效指标,TopoⅡ在乳腺癌中的表达可作为指导乳腺癌化疗的重要指标。     

乳腺癌bcl-2表达与患者预后相关因素关系的研究

目的：研究乳腺癌中bcl-2蛋白表达与患者生存期及其组织学分级、雌激素受体（ER）、p53、c-erbB-2等影响预后因素的分析。方法：采用免疫组化LSAB法检测bcl-2、ER、p53及c-erbB-2的表达，并分析其相关性及其与预后的关系。结果：bcl-2阳性表达率为50．27％（92／183），其表达与乳腺癌组织学分级、ER状态呈明显正相关，与p53及c-erbB-2表达呈明显负相关；bcl-2阴性者其总生存率及无瘤生存率均明显低于bcl-2阳性者。结论：bcl-2蛋白阴性的乳腺癌患者预后不好，这可能与bcl-2失表达肿瘤中，p53蛋白聚积、c-erbB-2过度表达以及ER的缺失有关；免疫组化检测bcl-2表达可为预测乳腺癌患者预后及选择内分泌治疗提供一个有实用价值的指标。     

乳腺癌bcl-2、Ki-67、p53表达及意义

目的：探讨bcl-2、Ki-67、p53蛋白在乳腺癌中的表达及其关系。方法：应用免疫组化SP方法，观察56例乳腺癌中的bcl-2、Ki-67、p53的表达情况。结果：bcl-2、Ki-67和p53在乳腺癌中表达率分别为63％，68％，52％，与乳腺癌分级及淋巴结转移密切相关（P＜0．05）。结论：bcl-2、Ki-67、p53的异常表达在乳腺肿瘤发生发展中起重要作用。     

bcl-6、p53、c-myc基因异常在弥漫大B细胞淋巴瘤中的临床意义

目的 探讨bcl-6 、p53、c-myc基因异常的检测在弥漫大B细胞淋巴瘤（DLBCL）中的临床意义.方法 间期荧光原位杂交（I-FISH）方法检测59例DLBCL患者活体石蜡组织bcl-6、p53蛋白、c-myc基因异常的情况,同时以CHOP及R-CHOP方案化疗,评价疗效.观察bcl-6、p53蛋白、c-myc基因与化疗疗效及生存期的关系.结果 59例DLBCL中,p53丢失18例（30.5％）,bcl-6重排11例（18.6％）,c-myc重排5例（8.5％）.p53丢失阳性组化疗有效率（33.3％）明显低于阴性组（76.5％）（x2=9.560,P=0.002）. bcl-6基因重排阳性组的预后差于基因重排阴性组,但差异无统计学意义[总生存（OS）,P=0.107;无进展生存时间（PFS）,P=0.094]; p53基因丢失阳性组预后明显差于阴性组（OS,P=0.031;IPFS,P=0.028）;c-myc重排阳性组的预后差于基因重排阴性组,但差异无统计学意义（OS,P=0.163;PFS,P=0.167）.其中CHOP化疗组患者,p53基因丢失、c-myc重排阳性组的预后明显差于阴性组,差异有统计学意义（P值均＜ 0.05）;R-CHOP化疗组,bcl-6基因重排阳性组具有较差的预后意义（OS,P=0.003;PFS,P=0.007）.结论 bcl-6 、p53、c-myc基因异常与 DLBCL预后密切相关,可作为预测DLBCL的预后因素并指导治疗.     

Thymidylate synthase expression, p53, bcl-2, Ki-67 and p27 in colorectal cancer: relationships with tumor recurrence and survival.

It was the objective to determine in this retrospective study whether thymidylate synthase (TS), p53, bcl-2, Ki-67 and p27 in Dukes' stage B and stage C (AJCC/UICC stage II and III) colorectal adenocarcinoma were predictive of disease-free survival (DFS) and overall survival (OS). Paraffin-embedded specimens from 103 patients with colorectal cancer, treated with surgery between October 1994 and September 1999, were examined for TS expression, p53, bcl-2, Ki-67 and p27 using immunohistochemistry; 51 cases were Dukes' stage B and 52 cases were Dukes' stage C disease. Adjuvant 5-FU-based chemotherapy was given to all patients, while 31 having rectal malignancy also received pelvic radiotherapy. Data were associated with the recurrence rate and survival. With a median follow-up of 5 years, 38 patients (36.8%) developed recurrence and as many patients (36.8%) died. TS was overexpressed in 16 cases (15.6%), p53 nuclear oncoprotein accumulation in >10% of cells occurred more frequently [61 of 103 cases (59.3%)], positive expression of bcl-2 protein in >10% of cells was observed in 41 of 103 cases (39.9%), 57 patients (55.4%) showed immunohistochemical expression of Ki-67 and there were 75 cases (72.9%) with p27 accumulation. The pathological stage was the only independent prognostic factor for DFS (p = 0.042). Sex, as well as age and biological prognostic factors, had no significant impact value on DFS and OS. A multivariate analysis of OS demonstrated that stage C, p53 negative and Ki-67 positive were associated significantly with an unfavorable outcome and a worse median OS (p = 0.035 and t ratio = 2.48). Some biological characteristics such as p53 and Ki-67 status may provide useful prognostic information in addition to the classical clinicopathological parameters. However, further studies are needed to clarify the value of adopting biological prognostic factors into clinical practice.     

Clinical significance of Ki-67 and p53 expression in curatively resected non-small cell lung cancer

The aim of this study is to explore the association of Ki-67 and p53 expression with prognosis in non-small cell lung cancer (NSCLC) patients who underwent curative resection. We retrospectively identified 116 consecutive patients with stages I–III NSCLC who underwent curative resection at a single center from January 2007 to December 2012. Ki-67 and p53 expression was assessed by immunohistochemistry. Data on clinicopathologic features and survival were collected retrospectively. Ki-67 expression in 109 samples and p53 expression in 115 patients were analyzed. According to the results, 108 patients (99 %) showed at least some expression of Ki-67. The median Ki-67 expression level was 30 %. Positive p53 expression was observed in 91 (79 %) patients. Higher Ki-67 expression (>40 %) was significantly more frequent in male (26 vs. 4 % in female, p?=?0.002), ever-smoker (31 vs. 10 % in never-smoker, p?=?0.024), and non-adenocarcinoma (30 vs. 11 % of adenocarcinoma, p?=?0.012) patients. In univariable analysis, median disease-free survival (DFS) was shorter with higher Ki-67 expression (16.1 vs. 61.9 months in those with lower Ki-67 expression, p?=?0.005), and p53 expression did not show an association with DFS. Among 42 patients with stage I NSCLC who did not receive adjuvant chemotherapy, DFS was significantly worse in patients with higher Ki-67 expression (2-year DFS rate 57 vs. 88 %, p?=?0.018). In a Cox regression model, higher Ki-67 expression (>40 %) was a significant independent prognostic factor associated with poorer DFS (HR 2.9, 95 % CI 1.3–6.2) along with TNM stage and age. Higher Ki-67 expression (>40 %) showed an independent association with shorter DFS in NSCLC patients who underwent curative resection.     

Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes' B2 or C colon cancer: a North Central Cancer Treatment Group Study.

PURPOSE: Molecular studies of colon cancer have provided insights into pathogenesis, yet it is unclear how important these markers are in predicting prognosis. This study investigated the prognostic significance of TUNEL, bcl-2, p53, proliferation marker Ki-67 and DNA mismatch repair (MMR) status in patients with Dukes' stage B2 and C colorectal adenocarcinomas. PATIENTS AND METHODS: Tumor tissue from 366 patients (75% Dukes' C, 25% Dukes' B2) from four randomized North Central Cancer Treatment Group phase III surgical adjuvant trials were used. Eighty-one percent of patients received adjuvant treatment, which was primarily fluorouracil (FU) based (90%). Tumor location was predominantly (87%) the colon. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Ki-67, p53, bcl-2, and MMR were assayed using immunohistochemistry. Stage, grade, MMR, Ki-67, and previously determined flow cytometry markers (ploidy and S phase) were explored for associations with each other and with overall survival (OS) and disease-free survival (DFS). RESULTS: Univariately, stage B2, low grade, diploid, Ki-67 more than 27%, normal p53, and FU-based adjuvant treatment were significantly associated with improved OS and DFS (P <.05). After adjusting for stage, grade, and ploidy in multivariate analysis, Ki-67 remained significantly related to both OS and DFS (P <.01). Active FU-based adjuvant treatment was significant only for OS in this multivariate model. Neither bcl-2 nor TUNEL were significant. CONCLUSION: This retrospective study indicates that Ki-67 and ploidy may have stronger prognostic impact on OS and DFS than other parameters investigated after adjusting for stage and tumor grade. Prospective studies to elucidate the mechanism and prognostic significance of these findings are necessary.     

Prognostic significance of Ki-67 nuclear proliferative antigen, bcl-2 protein, and p53 expression in follicular and diffuse large B-cell lymphoma

We analyzed 104 patients with non-Hodgkin’s lymphoma, follicular or diffuse large-B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty-nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p=0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p=0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p=0.03) and involvement of more than one extranodal area (p=0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p=0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p=0.02) and LDH (p=0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p=0.009).     

Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue

The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.     

Evaluation of putative molecular biomarkers in abdominal and retroperitoneal leiomyosarcomas.

AIMS: Leiomyosarcomas (LMS) are diverse tumours with different biological behaviour. To evaluate the biological nature of intraabdominal and retroperitoneal leiomyosarcomas we retrospectively examined the immunoreactivity of p53, bcl-2 and proliferative activity expressed as Ki-67-labelling index in 43 tumours. METHODS: Immunohistochemical staining was performed using a peroxidase-streptavidin method on paraffin-embedded sections using specific anti- p53, anti- bcl-2 and anti Ki-67 monoclonal antibodies. RESULTS: Of 43 tumours, seven were located in the stomach, 11 in the small or large bowel, 12 in the uterus, 11 in the retroperitoneum and two cases in the urinary bladder. Five-year disease-free survival was 46.5%. Twenty-three patients (53.4%) died of the disease. Positive immunoreactivity for p53 and bcl-2 was found in 18 (41.9%) and 26 patients (60.5%), respectively. Positive Ki-67 staining was observed in eight patients (18.6%). Proliferative indices were higher in LMS with high mitotic activity (P=0.004) and high grade (P=0.009). All Ki-67 positive LMS were intermediate or high-grade tumours. Ki-67-labelling index showed inverse relationship to bcl-2 expression. A trend towards higher survival and expression of bcl-2, p53 or Ki-67 was found. CONCLUSIONS: Our results demonstrate that p53 and bcl-2 are expressed in a substantial number of intraabdominal and retroperitoneal leiomyosarcomas. In our study, the expression of these biomarkers did not predict patient outcome. Higher Ki-67 labelling indices were found in more biologically aggressive leiomyosarcomas. Copyright Harcourt Publishers Limited.     

Expression of P53, P27 and KI-67 in colorectal cancer patients of various ethnic origins: clinical and tissue microarray based analysis

BACKGROUND: This study was conducted to determine survival according to the expression of molecular markers in colorectal cancer (CRC) patients of various ethnic origins. METHODS: Resection of primary tumor was conducted on 171 patients with CRC. Corresponding archived paraffin-embedded blocks were retrieved and tissue microarray (TMA) constructed. Immunohistochemical staining of the TMA for p53, p27 and Ki-67 was quantified by two independent pathologists. Survival was analyzed using the Kaplan-Meier product limit method. RESULTS: With a median follow-up of 65 months, 56 patients (32.7%) died of disease. AJCC stage correlated with disease-free (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). IHC staining was positive for Ki-67 in 77.4%, p53 in 55.8% and p27 in 54.2% of patients. Primary tumor marker expression did not correlate with DFS or OS. The 5-year DFS for Ashkenazi Jews was 75%, significantly higher than Sephardic Jews (SJ) 64% and Palestinian Arabs (PA) 38%, P = 0.001. CONCLUSIONS: Ethnicity among Ashkenazi and SJ and PA appears to have a significant impact on disease outcome in patients with CRC patients, while primary tumor expression of p53, p27 and Ki-67 was unrelated to disease outcome.     

Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar.

: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis.

: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p = 0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p = 0.04), and these patients had a higher rate of nonbrain distant metastases (p = 0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p = 0.01). There was a positive correlation in the expression of Ki-67 (p = 0.02)(r² = 0.1608), as well as p53 (p < 0.001) (r² = 0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive.

: Differences in biomarker expression between the case and control groups did not serve as significant predictors of brain metastasis or patient survival. There was a strong correlation between lung primary biomarker expression and brain metastasis expression for Ki-67 and p53. Univariate analysis showed that low p53 and high Ki-67 expression predicted poor prognosis. This study shows that there may be a strong correlation between biomarker expression in non-small-cell lung cancer primary tumors and their brain metastases.     

Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma

BACKGROUND AND OBJECTIVES: To investigate the immunohistochemical expression of three apoptosis-related genes (bax, bcl-2, and p53) and apoptosis (TUNEL) in patients with primary osteosarcoma, and examine potential correlations between gene expression and clinicopathological characteristics in these patients. MATERIALS AND METHODS: Thirty-five primary osteosarcoma specimens and 18 tissue specimens deriving from non-malignant osseous lesions were immunohistochemically stained for bax, bcl-2, and p53 proteins, while apoptosis was investigated by the TUNEL method. The results were statistically analyzed. RESULTS: P53, bax, and bcl-2 protein expression was observed in 22 (62.9%), 29 (82.9%), and 18 (51.4%) osteosarcoma patients, respectively. Non-specific positive TUNEL staining (+/-) was observed in two primary osteosarcoma cases (5.7%). None of the benign controls expressed any of the genes studied. None of the apoptosis-related genes studied was able to predict overall or disease-free survival in our group of patients. Nevertheless, increased bax/bcl-2 protein expression ratio was associated with a decreased 4-year survival and disease free survival (P = 0.0229 and P = 0.0370, respectively). Furthermore, all the patients who were bax(+)/bcl-2(-)/p53(+) relapsed within the 4-year follow-up period (P = 0.0385). CONCLUSIONS: The increased apoptotic rate as determined by an elevated bax/bcl-2 protein expression ratio or by the bax(+)/bcl-2(-)/p53(+) protein expression pattern, appears to identify groups of osteosarcoma patients with unfavorable prognosis.     

Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up

We performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.