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.     

Ki-67、p53、bcl-2的表达与恶性淋巴瘤自体造血干细胞移植预后的相关性

 目的　研究bcl-2、p53、Ki-67在恶性淋巴瘤组织中的表达以及与自体造血干细胞移植（AHSCT）预后的相关关系。方法　采用免疫组织化学IHC法检测33例行AHSCT治疗的患者淋巴瘤组织切片中Ki-67、p53、bcl-2的表达。并分析Ki-67、p53、bcl-2的表达与预后的相关性。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　p53 的表达与33例AHSCT患者预后无关,bcl-2阳性表达组和阴性表达组移植后3年无瘤生存率（DFS）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DFS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。COX多因素分析显示,Ki-67和bcl-2是影响淋巴瘤患者AHSCT后无瘤生存的相关因素（P＝0.0437）。结论　bcl-2、Ki-67蛋白阳性表达的淋巴瘤患者,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是影响淋巴瘤患者AHSCT无瘤生存的独立相关因素。     

survivin、bcl-2及ki-67在弥漫大B细胞淋巴瘤中的表达及临床意义

目的:研究弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)对化疗不敏感和复发现象是否与凋亡抑制因子survivin、bcl-2蛋白及增殖因子ki-67蛋白的表达有关。方法:收集2000-2003年本院收治的经病理学证实的DLBCL患者,符合入组条件41例,分析IPI各因素及疗效与预后之间的相关性。同时,20例可获取病理组织标本的患者,用免疫组化方法进行survivin、bcl-2及ki-67蛋白表达的测定,并对其进行预后相关性分析。结果:单因素分析显示临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平及疗效均为DLBCL的独立预后因素,是否合并放疗或使用美罗华对预后影响无统计学差别;多因素分析提示ECOG评分与疗效是影响无进展生存的独立预后因素。免疫组化分析显示ki-67乘积高的患者生存期较短(P<0．05),复发组的平均ki-67指数及bcl-2乘积较未复发组高(前者P<0．05,后者P=0．069),bcl-2乘积高的患者死亡率较高(P<0．05),survivin核阳性患者较核阴性患者生存期短,但差异未达到统计学意义(P>0．05)。结论:临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平、疗效及ki-67均为DLBCL的独立预后因素,Ki-67指数高为复发危险因素,bcl-一2乘积高为预后危险因素,survivin核阳性可能是预后不良因素。     

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.     

Minichromosome maintenance 2 (MCM2) immunoreactivity in stage III human gastric carcinoma: clinicopathological significance

Background The origin licensing factor minichromosome maintenance 2 (MCM2) has recently been identified as a critical regulator of proliferation in both normal and neoplastic cells. This study examined whether MCM2 expression was of prognostic relevance in patients with stage III gastric carcinoma and whether the expression of this marker showed any correlation with clinicopathological characteristics. In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki-67, in gastric carcinoma. Methods We examined the immunohistochemical expression of MCM2, Ki-67, and p53 in 103 surgically removed stage III gastric carcinomas, which consisted of 60 intestinal-type and 43 diffuse-type carcinomas. The labeling indices (LIs) of MCM2 and Ki-67 in cancer cells were compared with clinicopathological characteristics, p53 expression, and overall survival rates. Results The mean MCM2 and Ki-67 LIs were 69.1 ± 11.8% and 48.2 ± 14.5%, respectively, in the intestinal carcinomas, and 43.7 ± 9.9% and 24.9 ± 11.0%, respectively, in the diffuse carcinomas. The LIs of these proteins revealed no significant association with clinicopathological characteristics or with p53 expression in the carcinomas. Kaplan-Meier survival curves showed that, in the patients with diffuse carcinoma, those with higher MCM2 LIs had a poorer prognosis (P < 0.05), but the MCM2 LI was not correlated with prognosis for those with intestinal carcinoma (P = 0.25). Ki-67 expression had no significant correlation with prognosis in either intestinal-type or diffuse-type carcinomas. Multivariate Cox regression analysis confirmed that MCM2 was an independent prognostic factor in patients with diffuse carcinoma. Conclusion Our data suggest that MCM2 is a useful prognostic marker in patients stage III diffuse-type gastric carcinoma.     

p53 、Ki-67 在弥漫性大B 细胞淋巴瘤中的表达及相互关系

 目的 探讨p53和Ki-67在DLBCL免疫类型中的表达及相互关系。方法 采用免疫组化MaxVision法检测p53和Ki-67在DLBCL免疫类型中和反应性增生的淋巴结中的表达。结果 25例GCB中p53的阳性率为16．0％，35例non-GCB中p53的阳性率为45．7％，两者之间P〈0．01；25例GCB中Ki-67高表达4例，35例non-GCB中Ki-67高表达18例，两者之间P〈O．01；p53阳性DL-BCL20例中ki-67高表达12例，p53阴性DLBCL40例中Ki-67高表达10例，两者正相关。结论 p53、Ki-67的表达与DLBCL的免疫类型相关，GCB类型中低表达，non-GCB类型中高表达。     

Divergent Squamous Differentiation in Upper Urothelial Carcinoma—Comparative Clinicopathological and Molecular Study

Upper urothelial carcinoma (UUC) has a plasticity to demonstrate divergent differentiation with squamous metaplastic elements. There was no previous study exploring profiling of molecular markers in metaplastic squamous upper urothelial carcinoma (SUUC) and conventional upper urothelial carcinoma (CUUC). The aims of this study was to compare expression of the phenotypic characteristics of tumors and molecular markers (p53, p16, cyclin D1, E-cadherin, HER-2, Ki-67, Bcl-2, Bax) in SUUC and CUUC. SUUC was detected in 20% of 44 patients. There was significant difference between SUUC and CUUC in the pathological stage, grade, growth and presence of lymphovasular invasion (p < 0.05; 0.05; 0.05; 0.01 respectively). The mean Ki-67 and p53 labeling index was significantly higher in SUUC than in CUUC (p < 0.05; 0.05). There was no significant difference in the expression of p16, cyclin D1, E-cadherin, HER-2, Bcl-2 and Bax between SUUC and CUUC. Univariant model showed that SUUC was significantly associated with lymphovascular invasion (p = 0.007), Ki-67 activity (p = 0.016) and growth (p = 0.026). Exploration of UUC with squamous divergent differentiation showed changes in phenotypic characteristics and Ki-67, as well as similar molecular profile with CUUC.     

Ki-67 expression is predictive of prognosis in patients with stage I/II extranodal NK/T-cell lymphoma, nasal type.

BACKGROUND: Localized extranodal natural killer (NK)/T-cell lymphoma, nasal type, commonly has a low or low-intermediate risk of the international prognostic index (IPI), so the IPI has shown inconsistency in predicting prognosis. Thus, we analyzed Ki-67 expression and proposed a new prognostic model including Ki-67 expression for stage I/II extranodal NK/T-cell lymphoma. PATIENTS AND METHODS: We studied Ki-67 expression and its relationship with prognosis in 50 patients with extranodal NK/T-cell lymphoma. RESULTS: The patients were dichotomized by the median value: low (<65%) versus high Ki-67 (> or =65%). High Ki-67 was associated with a worse overall survival (OS; P = 0.021) and disease-free survival (DFS; P = 0.044). In multivariate analysis, Ki-67 expression and primary site of involvement were found to be an independent prognostic factor for OS and DFS (P < 0.05). Based on these results, we proposed a new clinico-pathological prognostic model with Ki-67 expression and the primary site of involvement. It showed a high degree of correlation with worse OS and DFS (P < 0.001). CONCLUSIONS: Ki-67 expression is predictive of prognosis, and our prognostic model may become a useful tool for predicting prognosis in patients with stage I/II extranodal NK/T-cell lymphoma, nasal type.     

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。     

Primary follicular lymphoma of the testis in childhood

BACKGROUND: Follicular lymphoma in childhood is rare. The authors present four unusual primary follicular lymphomas of the testis in children. METHODS: Tumor tissue was evaluated using light microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) and bcl-2 gene rearrangements. Southern blot and immunohistochemical analyses were used to detect bcl-6 gene rearrangements and protein expression, respectively. RESULTS: Four young boys ranging in age from 3 to 10 years were diagnosed with Stage IE follicular large cell lymphoma (Grade 3). A B-cell phenotype was documented in all four cases; monoclonality was confirmed in three cases by demonstration of light chain restriction or clonal IgH gene rearrangement. None of the lymphomas expressed Bcl-2 or p53 protein, and bcl-2 gene rearrangements were not found in the three lymphomas studied. In contrast, Bcl-6 protein was expressed by all three lymphomas studied, and a bcl-6 gene rearrangement was detected in the one case analyzed by Southern blot. All four boys were treated by orchiectomy and combination chemotherapy and are alive with no evidence of disease 18-44 months following their initial diagnoses. CONCLUSIONS: Follicular lymphomas may rarely occur as primary testicular tumors in prepubertal boys and, when localized, appear to be associated with a favorable prognosis. In contrast to follicular lymphoma in adults, pediatric follicular lymphomas of the testis are usually of large cell type (Grade 3) and lack bcl-2 or p53 abnormalities. The identification, in one case, of a bcl-6 gene rearrangement suggests an alternate molecular pathogenesis for pediatric follicular lymphoma.     

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.     

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.     

老年弥漫大B细胞淋巴瘤预后影响因素

目的:探讨老年弥漫大B细胞淋巴瘤预后影响因素。方法:回顾性分析2011年1月-2013年4月104例老年弥漫大B细胞淋巴瘤患者危险因素。结果:疗效上,总有效率为70.19%,进展为29.81%;在预后进展患者中,临床分期、IPI评分、GCB、LDH、Ki-67是老年弥漫大B细胞淋巴瘤预后进展影响因素,同时也是高危影响因素（P均<0.05）,而和性别、结外侵犯、bcl-2、bcl-6、B症状、ECOG评分无关（P＞0.05）。结论:影响老年弥漫大B细胞淋巴瘤预后的影响因素和患者具体疾病情况密切相关,应重视患者实际情况并选择恰当的治疗方案。     

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.     

Plenary lectures

Cyclooxygenase-2 (COX-2) is an important factor in gastric carcinogenesis, and COX-2 expression in gastric cancer patients correlates with prognosis. We have now studied the impact of COX-2 in comparison to six other tissue tumor markers, DNA index, and S-phase fraction (SPF) in a large series of gastric cancer specimens. From 342 consecutive patients, 337 archival tissue specimens were available for immunohistochemistry of COX-2, HuR, cyclin A, MMP-2, p53, p21, and Ki-67 and 313 for analysis of DNA index and S-phase fraction by flow cytometry. Associations between factors were assessed by chi-square test and survival analysis by the Kaplan–Meier method and Cox model. A significant association emerged between of COX-2 and p53 (p < 0.0001), Ki-67 (p = 0.013), DNA ploidy (p < 0.0001), and SPF (p < 0.0001). In an extended multivariate analysis, COX-2 and p53 expression were independent prognostic factors for poor survival, in addition to high stage and non-curative surgery. In gastric cancer, COX-2 expression associated with markers for apoptosis and proliferation, and furthermore, it was confirmed that COX-2 and p53 are strong prognostic indicators.     

Potential role of bcl-2 as a suppressor of tumour angiogenesis in non-small-cell lung cancer

It has been reported that genes regulating apoptosis may play a role in tumoral angiogenesis. This study examined the relationship between tumour vascularization, a measure of tumour angiogenesis, and bcl-2 and p53 expression in operable non-small-cell lung cancer (NSCLC). The relationship between bcl-2, p53 and tumour vascularization and epidermal-growth-factor-receptor(EGFR) and c-erbB-2 expression was also studied. Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl-2, p53, EGFR and c-erbB-2 expression. bcl-2 expression was found in 20/107 (19%) cases and was associated with squamous-cell histology (p = 0.03). A strong inverse relationship was found between bcl-2 expression and vascular grade (p = 0.005). All c-erbB-2-positive cases were negative for bcl-2 expression (p = 0.01). Overall no association was found between c-erbB-2 expression and vascular grade. However, in bcl-2-negative cases positive c-erbB-2 expression correlated with low angiogenesis (p = 0.05). No relationship was found between p53 and EGFR expression and bcl-2, c-erbB-2 or vascular grade. The improved prognosis reported in bcl-2-positive NSCLC may be related to low tumour vascularization. The results suggest that the anti-apoptotic gene bcl-2 plays a role in regulating tumour angiogenesis. Since normal lung epithelium expresses bcl-2, a sequence of tumour progression involving loss of bcl-2, then activation of c-erbB-2 or increase in tumour vascularization is proposed. Int. J. Cancer 74:565–570, 1997.© 1997 Wiley-Liss, Inc.     

Enhanced apoptosis correlates with poor survival in patients with laryngeal cancer but not with cell proliferation,bcl-2 or p53 expression

The purpose of the current study was to analyse apoptosis and bcl-2 expression in laryngeal squamous cell carcinoma (SCC) with special reference to their prognostic significance, correlation with the clinical and pathological characteristics as well as cell proliferation and p53 accumulation. 172 patients with primary laryngeal SCC were followed-up for a median of 67 months. The volume corrected apoptotic (A/V) index was analysed using an in situ end labelling method (TUNEL) in 85 randomly selected patients. The expression of bcl-2 and p53 was analysed with monoclonal antibodies. The proliferative activity was measured both with Ki-67 (MIB-1) antibody and the volume corrected mitotic (M/V) index. The A/V index was not associated with p53 (P=0.6) or bcl-2 (P=0.6) expression or with proliferative parameters (P=0.9 for M/V and P=0.3 for MIB-1). The 10-year overall survival in patients with a high A/V index was poorer when compared with patients with a low index (47% versus 81%, P=0.005), while accumulation of bcl-2 had no prognostic significance (P=0.5). In Cox multivariate analysis of the whole cohort, stage (P<0.0005) and histological grade (P=0.04) were predictors of overall survival. In the subset of patients with an A/V index available, predictors of survival were stage (P=0.05), A/V index (P=0.02) and histological grade (P=0.04). A high A/V index was an independent predictor of poor survival in laryngeal SCC. This effect was not associated with tumour cell proliferation. Accumulations of p53 and bcl-2 were not associated with apoptosis. Expression of bcl-2 lacks any prognostic significance in laryngeal SCC. We propose that assessment of the A/V index may help in selecting patients with poor prognosis.     

A PCR analysis of bcl-2 gene rearrangement in nodal and extranodal non-hodgkins-lymphoma (nhl) - some unusual observations in saudi patients

Non-Hodgkin's lymphoma (NHL) is the most common malignancy referred to our institute which is the largest tertiary referral cancer centre in Saudi Arabia, The proportion of follicular low grade NHL appears to be extremely small in this population (<5% of all NHL). To date, there is no data available regarding any correlation between bcl-2 gene rearrangement and different cell types of nodal and extranodal NHLs in Saudi patients. We used a sequential polymerase chain reaction (PCR) technique to determine the frequency of bcl-2/J(H) recombination occurring via the major breakpoint region (mbr) in 16 GI tract NHLs including 4 MALT lymphomas and 13 follicular (nodal) NHLs. The results showed only 2/13 (15%) nodal follicular NHLs with bcl-2/J(H) fusion DNA whereas 9/16 (56%) of the extranodal NHLs with at least 2 of them exhibiting MALT characteristics were positive for the bcl-2 gene rearrangement. A breakdown of the proportion of extranodal NHLs of different cell types showing bcl-2 rearrangement via mbr was as follows: 5/8 diffuse large non-cleaved cell (DLNCC), 1/3 diffuse small cleaved cell (DSCC), 1/1 follicular small cleaved cell (FSCC) and 2/4 MALTs. The PCR amplified bcl-2/J(H) fusion DNA from 5 randomly selected tumors (2 MALTs, 1 DLNCC, 1 DSCC and 1 nodal follicular lymphoma) were cloned and sequenced. All 5 of them showed different bcl-2/J(H) N-regions confirming the clonality of each tumor sample. The data indicating a very low incidence of bcl-2 translocation in nodal follicular NHLs and a surprisingly high incidence of it in extranodal NHLs are intriguing, and quite contrary to the findings in Western patients. These unusual observations warrant further studies and may suggest that different genetic events are involved in the development of extranodal NHLs including MALT and follicular center-cell NHLs in Saudi patients.     

Alterations in the p53 pathway and prognosis in advanced ovarian cancer: a multi-factorial analysis of the EORTC Gynaecological Cancer group (study 55865)

PurposeThe study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865.Experimental designRetrospectively collected paraffin blocks from 169 patients with stages IIb–IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC).ResultsExpression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36–0.94, p = 0.025) in addition to FIGO stage (HR 1.54, CI 1.08–2.21, p = < 0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors.ConclusionP21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.     

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.