Prognostic significance of p53, bax and bcl-2 gene expression in patients with laryngeal carcinoma.

AIM: This study was designed to examine the prognostic significance of the coexpression of three genes (bax, bcl-2 and p53) which play a critical role in the apoptotic mechanisms in patients with squamous cell laryngeal carcinoma. MATERIALS AND METHODS: The immunohistochemical expression of bcl-2, bax and p53 genes was retrospectively examined in 38 patients with squamous cell laryngeal carcinoma and in five controls (necrotomic tissue). Tissue specimens were obtained both during the diagnostic biopsy and at the time of surgery. Clinicopathological and survival data were correlated with the staining results. RESULTS: Bcl-2 protein expression (P=0.0472), stage (P=0.0087) and lymph-node involvement (P=0.0488) were found to be independent prognostic factors. Increased bcl-2 protein expression correlated with a better 5-year survival (P=0.0472). Patients who were bcl-2(-)/p53(-) (n=25) or bax(+)/bcl-2(-) (n=13) had a significantly worse overall survival (P=0.0305 and P=0.0482, respectively). Similarly, patients who were bax(+)/bcl-2(-)/p53(-) (n=11) also had a worse 5-year survival compared with the rest of the group (P=0.0088). Changes that were noticed in bax and p53 protein expression from the time of biopsy until the time of surgery did not correlate with a significant increase in the overall survival. CONCLUSIONS: The expression of bcl-2 gene appears to be an independent prognostic factor for patients with laryngeal carcinoma. The coexpression of the genes studied can be used to determine aggressive clinical phenotypes.     

Prognostic value of bax, cytochrome C, and caspase-8 protein expression in primary osteosarcoma

The prognostic significance of bax, cytochrome c, and caspase-8 in patients with primary osteosarcoma is unknown. We examined the immunohistochemical expression of these genes in 35 surgically treated patients with primary osteosarcoma. Clinicopathological and survival data were correlated with the staining result. Eighteen tissue specimens from non-malignant osseous lesions were used as controls. Bax, cytochrome c, and caspase-8 positive staining was observed in 29 (82.9%), 16 (45.7%), and 0 (0%) patients, respectively, but did not stain any of the 18 benign osseous lesions used as controls. None of the genes studied predicted overall or disease-free survival. Patients, however, bearing bax(+)/cytochrome c(+) or bax(+)/cytochrome c(+ +) tumors had a decreased 4-year disease-free survival rate compared to the rest of the group (p = 0.0489 and p = 0.0208, respectively), identifying two groups of patients where more intensive adjuvant treatment could possibly be applied to prevent high postoperative recurrence rates.     

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

The clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short- and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated.     

Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer.

bcl-2 is one of a family of genes that control the apoptotic threshold of a cell. bcl-2 protein and its anti-apoptotic homologue, mcl-1, with the pro-apoptotic protein, bax, are thought to function by forming homo- and heterotypic dimers that then control the progression to apoptosis. p53 is also involved as a down-regulator of bcl-2 and a promoter of bax. To determine the effect of these apoptotic mechanisms, we used immunohistochemistry to determine the prognostic significance of the expression of bcl-2, mcl-1, bax and p53 in primary and recurrent cervical cancer. Tissues from 46 patients with primary cervical cancer and 28 women with recurrent carcinoma were stained for bcl-2, mcl-1, bax and p53. Kaplan-Meier survival analysis was performed using the log-rank test for differences between groups. In the primary disease group, positive staining for bcl-2 was associated with a better 5-year survival (bcl-2 +ve, 84% vs bcl-2 -ve, 53%, P = 0.03). Positive staining for p53 was associated with a survival disadvantage (p53 +ve, 4-year survival 38% vs p53 -ve, 4-year survival 78%, P = 0.02). mcl-1 and bax staining were not useful as prognostic indicators in primary disease. No marker was prognostic in recurrent disease. Positive bcl-2 staining defines a group of patients with primary disease with a good prognosis. p53, an activator of the bax promoter, identifies a group with a worse outcome. In recurrent disease, none of the markers reflected prognosis.     

p53基因诱导胱癌细胞HTB9凋亡及相关基因的表达

目的 研究野生型p53基因诱导膀胱癌细胞凋亡的作用,及其对凋亡相关基因bcl-2、bax和ICE表达的调控。方法 将野生型p53基因重组腺病毒载体转染人膀胱癌细胞HTB9,应用RT－PCR检测bax的mRNA表达水平,应用免疫组化法检测bcl-2、bax和ICE蛋白表达水平,以DNA琼脂糖凝胶电泳、脱氧核苷酸转移酶介导的dUTP切口末端标记技术（TUNEL）和流式细胞仪检测细胞凋亡。结果 野生型p53基因导入可诱导HTB9细胞凋亡,凋亡细胞百分率可达50．4％;bax mRNA和蛋白水平增高,ICE和Bcl-2蛋白水平分别增高和下降。结论 野生型p53基因很可能是通过调控凋亡相关基因ICE、Bax和Bcl-2的表达来诱导细胞凋亡。     

TgN(p53mt_LMP1)/HT小鼠鼻腔和鼻咽黏膜上皮细胞增殖与凋亡相关基因表达的关系

背景与目的： 探讨TgN(p53mt_LMP1)/HT小鼠鼻腔和鼻咽黏膜上皮癌前病变发生与细胞周期分布,凋亡相关基因bax、bcl_2和增殖相关基因PCNA的表达水平及它们与p53mt基因表达的相关关系。 材料与方法： HE染色法观察G4代12月龄TgN(p53mt_LMP1)/HT转基因阳性和阴性小鼠鼻腔和鼻咽黏膜上皮病理组织学变化,流式细胞术测定细胞周期分布特点,免疫组织化学法检测组织中p53mt、bax、bcl_2和PCNA表达水平,综合分析其相关性。 结果： 转基因阴性小鼠和阳性小鼠鼻腔或鼻咽黏膜上皮癌前病变发生率分别为0和63.64％(P<0.01)。与转基因阴性小鼠比较,转基因阳性小鼠鼻腔和鼻咽黏膜上皮组织G0/G1期细胞数量减少,S期、G2/M期细胞数量增多,细胞增殖指数增高(P均<0.01),p53mt、bcl_2和PCNA表达水平显著增高(P<0.01),bax表达水平显著降低,bcl_2/bax比值升高(P<0.01)。 结论： TgN(p53mt_LMP1)/HT转基因阳性小鼠p53mt的表达可引起bax表达抑制,bcl_2表达水平增高,bcl_2/bax比值升高,PCNA表达增强,由此导致细胞凋亡活性降低,细胞增殖活性升高,细胞转化机率增加,可能与鼻腔或鼻咽黏膜上皮癌前病变有密切关系。     

The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer.

PURPOSE: The purpose was to evaluate the utility of some bcl-2 family proteins fas and fasL as predictive indicators for chemotherapy response in advanced breast cancer. EXPERIMENTAL DESIGN: Between October 1994 and October 1997, 283 patients with advanced breast cancer were included in a multicenter randomized study comparing docetaxel (D) to sequential methotrexate and 5-fluorouracil (MF) after anthracycline failure. The response rates (complete response + partial response) were 42 and 21% in the D and MF arms, respectively (P < 0.001). In 126 patients, histological blocks of primary tumors were available for immunohistochemical analysis of bax, bcl-2, bcl-xL, bag-1, fas and fasL. RESULTS: Of the investigated factors, bag-1 correlated positively with bax, bcl-2, and fasL, and fasL correlated positively with fas and bax. None of these apoptosis-related factors was associated with a response to chemotherapy either in the whole patient population or in the D or MF arms. Interestingly, low bcl-2 expression was associated with shorter time to progression (P = 0.02) and shorter overall survival (OS; P = 0.001). High fasL expression showed a trend toward shorter OS. In multivariate backwards stepwise Cox analysis, in which histological grade and estrogen receptor status (ER) were also included, bcl-2 (P = 0.01) and fasL (P = 0.005) remained highly significantly associated with OS, whereas histological grade and ER lost their significance. CONCLUSIONS: None of the investigated apoptosis-related factors of primary tumor could predict the later response to either D or MF treatment. However, fasL and bcl-2 were strong prognostic factors. Patients who had tumors with high fasL and low bcl-2 expression had the shortest OS.     

Angiogenesis and apoptosis-related protein (p53, bcl-2, and bax) expression versus response of gastric adenocarcinomas to paclitaxel and carboplatin chemotherapy

The role of angiogenesis and apoptosis-related proteins in defining response to chemotherapy is poorly understood. We examined the microvessel density (MVD) and the expression of p53, bcl-2, and bax proteins in a series of 28 locally advanced gastric adenocarcinomas, treated with paclitaxel and carboplatin. A strong cytoplasmic reactivity in more than 10% of cancer cells was recorded in 25% of cases for p53 protein, and in 14% and 64% of cases for bcl-2 and bax proteins, respectively. Microvessel density was assigned in three categories: low (<35), medium (35-60), and high (>60). Tumors of medium MVD showed a significantly higher response rate compared with those of high or low MVD (p = 0.01 and 0.001, respectively), and prognosis was significantly better in this group of patients with medium MVD tumors (p < 0.02). Loss of bax protein expression was somewhat more frequent in tumors resistant to chemotherapy, but this difference was not of statistical significance. Nuclear p53 reactivity was associated with higher MVD (p = 0.02). The expression of p53 and bcl-2 did not influence the outcome of treatment. The present study suggests that although apoptosis-related proteins may have a role in defining response to taxanes, parameters related to tumors' vasculature, such as drug availability or angiogenic tissue regeneration, may be equally important.     

Prostate tumours from an Asian population: examination of bax, bcl-2, p53 and ras and identification of bax as a prognostic marker

Molecular studies have suggested that ethnicity may play a significant role in prostate tumorigenesis, but no information exists for groups other than Caucasian or Japanese patients. We examined 62 archival samples of prostate tumours from Asians of non-Japanese origin for the over-expression of p53, for the possible presence of mutated ras genes, for the overexpression of the bcl-2 and bax proteins, as well as directly for the presence of apoptotic cells by the TUNEL methodology. Gene lesions of both ras (0%) and p53 (3%) were rare. While bcl-2 expression was not observed in any sample, bax expression was noted in 76% of samples and was associated with a significantly worse patient prognosis both overall (P< 0.005) and specifically in Chinese patients (P< 0.02). Apoptotic cells were found in 61% of samples, and were significantly associated with the presence of bax expression (P = 0.002), but not patient survival. These results suggest that prostate tumours from non-Japanese Asians are genetically distinct from prostate tumour found in both Japanese and Caucasian patients, and that treatment modalities may need to be tailored for specific population groups.     

Expression of bcl-2 and bax in chewing tobacco-induced oral cancers and oral lesions from India

Deregulation of oncogenes and tumor suppressor genes involved in apoptosis has been associated with tumor development and progression. To investigate the involvement of apoptosis regulating proteins in oral cancer in Indian patients, primarily associated with chewing tobacco habits, immunohistochemical expression of bcl-2 and bax was examined in 63 oral squamous cell carcinomas, and 31 putative premalignant lesions. Our studies revealed overexpression of tumor specific cytoplasmic bcl-2 in 56% and bax in 43% oral cancers. The oral cancers in the Indian patients are preceded by premalignant oral lesions; hence oral lesions were examined for bcl-2 and bax expression. We observed aberrant expression of bcl-2 in 16% oral lesions comprising leukoplakias and SMF and bax in 55% oral lesions. We have already reported, p53 expression in these oral cancers and lesions. It was noteworthy that 30% oral cancers demonstrated a p53+bcl2+ pattern, and 14% samples exhibited p53+bcl2+bax+ pattern. However, none of the oral lesions showed concurrent deregulation of p53 and bcl-2 or all the three genes. Interestingly 45% oral lesions were p53-bax+ as compared to 18% oral cancers; while 39% oral lesions were bcl2-bax+ as compared to 14% oral cancers, indicating overexpression of bax in oral lesions, in the absence of p53 and bcl-2 proteins. Significant correlation was observed between positive nodal status and bcl2+ (p=0.047) and p53+bcl-2+ (p=0.01) in oral cancers. Kaplan Meier survival analysis showed significantly (p=0.059) higher survival in patients with p53- oral tumors than with p53+ tumors. Our studies thus indicate frequent overexpression of apoptosis regulators bcl-2, bax and p53 proteins in oral cancers, and a subset of oral lesions, representing early events in oral car-cinogenesis. The aberrant bcl-2 expression and loss of p53 function observed, may play an important role in the tumorigenesis of oral cancers by allowing escape from apoptosis and enabling additional genetic alterations to accrue.     

Prognostic significance of apoptosis related gene family bcl-2 in human breast cancer

Bcl-2 family proteins appear to regulate apoptosis,with hcf-2, hcf-xl function as suppressors of apoptosisand bax, hcf-xs as promoters of cell death.ll] Theprognostic significance of these proteins in breast cancerhas been reported, but a comprehensive study is needed.In the present study, we have investigated the expressionof hcf-2, bax, hcf-xl in this multigene family, as regardsto their prognostic value in breast cancer.MATERIALS AND METHODSPatientsNinety-one breast cancer patients …     

Expression of Bcl-2, Bax and p53 proteins in pituitary adenomas: an immunohistochemical study

AIMS AND BACKGROUND: Although pituitary adenomas are usually benign lesions, their growth rate is highly variable and unpredictable. Apoptosis appears to be an important process in neoplastic lesions. The purpose of this study was to investigate the expression of apoptosis-related proteins including Bcl-2, bax and p53 in pituitary adenomas and its correlation with hormone function, tumor size, local control, and proliferative activity. STUDY DESIGN: The expression of Bcl-2, Bax and p53 proteins and hormonal function were determined in formalin-fixed, paraffin-embedded tissue from 41 untreated pituitary adenomas using immunohistochemistry. The patients were followed for a median of 60 months (range, 12 to 95). Patient charts were reviewed to record tumor recurrence and size. Tumor proliferative activity was assessed by immunohistochemistry using Ki-67 antibody. RESULTS: Of 41 pituitary adenomas, 26 (63%) were hormone-secreting and 15 (37%) non-functioning, 34 (83%) were macroadenoma and 7 (17%) microadenoma, and 15 (37%) showed local relapse. Six (14%) adenomas were of low proliferative activity, whereas the others (86%) were non-proliferative. Immunohistochemically, 31 adenomas (75%) showed bcl-2 positivity, 37 (90%) bax positivity, and 7 (17%) p53 positivity. Statistical analysis revealed that Bcl-2 protein expression significantly diminished in prolactin-secreting and non-functioning adenomas (P = 0.005 and P = 0.006, respectively), and increased in growth hormone-secreting adenomas (P = 0.003). In addition, expression of bax protein significantly decreased in recurrent tumors, in contrast to p53 protein, which showed a significant increase (P = 0.03 and P = 0.002, respectively). CONCLUSIONS: We think that apoptosis-related proteins such as Bcl-2, Bax and p53 may be significantly related to hormone function and local control in pituitary adenomas.     

骨肉瘤细胞凋亡相关基因的表达及其临床意义

目的 探讨反映骨肉瘤预后的蛋白标记物。方法 对骨肉瘤石蜡组织作免疫组化和Tunel染色,研究p53 c-myc和bcl-2基因的表达与肿瘤细胞凋亡指数(Al)的关系,及其与病理类型和患者颅后的关系。结果 p53、c-myc和bcl-2的表达水平与细胞凋亡指数呈负相关,与病理类型无相关关性。p53、c-myc、bcl-2和细胞凋亡指数与患者远期生存密切相关。结论 p53、c-myc和bcl-2的表达水平以及细胞凋亡指数可作为判断骨肉瘤恶性程度和预后的指标,可指导临床进行治疗。     

survivin、p53和bcl-2蛋白在非霍奇金淋巴瘤的表达及其意义

 目的 探讨survivin、p53和bcl-2蛋白在非霍奇金淋巴瘤（NHL）中的表达与肿瘤细胞凋亡和预后的关系。方法 应用TdT介导的dUTP缺口末端标记（TUNEL）技术和免疫组织化学SP法,检测82例NHL和17例良性淋巴结病变中细胞凋亡和survivin、p53和bcl-2蛋白的表达水平。结果 40.2 %（33／82）NHL表达 survivin,在BCL、TCL的表达阳性率分别为46.5 %、33.3 %,而仅在11.8 %（2／17）良性淋巴结病变中弱阳性表达,二者差异有统计学意义（P＜0.05）,但与NHL的免疫表型无关（P＞0.1）。NHL中survivin的表达与突变型p53蛋白积聚（P＜0.05）和肿瘤细胞凋亡的下降相关（P＜0.001）,但与bcl-2蛋白表达无关（P＞0.1）,且阳性表达患者的平均生存时间明显短于无表达患者（P＜0.05）。结论 survivin基因可能通过其凋亡抑制功能在NHL的发生、发展中有一定作用,且其与突变型p53蛋白的积聚显著相关,但与bcl-2蛋白表达无关;并可能是NHL的一个新的预后不良因子。     

Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment.

BACKGROUND: Tumor proliferation and apoptosis may be influenced by the mdm-2 gene product, which can block the antiproliferative effects of p53. bcl-2, one of a family of related genes that regulates the apoptotic pathway, exhibits a negative influence. Both individual and cooperative effects of these gene products may affect the biological behavior of primary bladder cancers and long-term outcome to standard therapy. METHODS: This study retrospectively evaluated the association with survival of mdm-2, p53, and bcl-2 expression in 59 patients with muscle-invasive, node-negative transitional cell carcinoma (TCC) treated with neo-adjuvant chemotherapy followed by locoregional surgery. Each marker was defined as an altered phenotype if >or=20% malignant cells in the primary tumor exhibited staining; normal or minimal expression was defined as <20% cells exhibiting staining. RESULTS: Altered mdm-2, p53, and bcl-2 expression was observed in 37%, 54%, and 46% of patients, respectively. In single marker analysis, altered p53 expression correlated with long-term survival (P = 0.05) but mdm-2 (P = 0.42) or bcl-2 (P = 0.17) did not. In the multiple-marker analysis, a prognostic index simultaneously assessing mdm-2, p53, and bcl-2 correlated with survival (P = 0.01). The 5-year survival for patients in which all markers were normally expressed was 54% compared with 25% in those with all three markers aberrantly expressed. Patients with aberrant expression of either one or two markers had an intermediate 5-year survival (49%). There was no association of molecular markers either alone or in combination with pathologic downstaging after neo-adjuvant chemotherapy. CONCLUSION: The cooperative effects of phenotypes determined by mdm-2, p53, and bcl-2 expression may predict survival in patients with muscle-invasive TCC of the bladder.     

Biological markers as indicators of response to primary and adjuvant chemotherapy in breast cancer

Interest in translational studies on breast cancer is presently devoted to identify biological predictors of treatment response. In patients with operable breast cancer, subjected to primary and adjuvant chemotherapy, we analyzed the predictivity on objective clinical response and relapse-free survival of biological markers related to different cellular aspects and functions. Tumour proliferative rate (evaluated as the (3)H-thymidine-labelling index, TLI), oestrogen and progesterone receptors (ER and PgR, evaluated by the dextran-coated-charcoal method), nuclear DNA ploidy and the immunocytochemical expression of p53, bcl-2 and bax proteins were determined before primary treatment, at the time of diagnosis, and after primary chemotherapy, at surgery. Objective clinical response was significantly related only to pre-treatment p53 expression or PgR status, with a higher rate for tumours not expressing than for those expressing p53 (94% vs. 72%), as well as for PgR-negative (PgR(-)) than for PgR-positive (PgR(+)) tumours (86% vs. 68%). In the overall series, 8-year clinical outcome was significantly related only to post-treatment steroid receptors. In particular, higher 8-year relapse-free survival rate was observed for patients with ER(-) or PgR(-) than for those with ER(+) (64% vs. 38%) or PgR(+) (53% vs. 37%) tumours. Such findings held true even within the sub-set of patients who received adjuvant post-operative chemotherapy, i.e., those with node-positive (N(+)) or ER(-)/node-negative (N(-)) tumours, among whom also rapid proliferation or the presence of apoptosis-favouring markers (bcl-2(-) or bax(+), singly and in association) on surgical specimens identified a sub-set of women who benefited from systemic treatment. The different biological markers were variously indicative of clinical outcome, with a predictivity on tumour shrinkage for p53 and PgR, detected before primary chemotherapy, and on long-term follow-up for ER, PgR and, to a lesser extent, TLI and apoptosis-modulating markers. Int. J. Cancer (Pred. Oncol.) 84:580-586, 1999.     

bcl-2、p53蛋白表达在卵巢子宫内膜异位症癌变过程中的作用

目的 探讨p53、bcl-2蛋白表达在卵巢子宫内膜异位症（内异症）癌变过程中的作用。方法 采用免疫组化法检测卵巢子宫内膜异位症组（内异症组,22例）、卵巢异位子宫内膜腺上皮不典型增生组（不典型增生组,14例）、卵巢子宫内膜异位症癌变组（癌变组,22例）的p53、bcl-2蛋白表达。结果 癌变组bcl-2蛋白表达阳性率显著高于内异组（P＜0．05）,不典型增生组bcl-2 蛋白表达阳性率显著高于内异组（P＜0．01）;癌变组p53蛋白表达阳性率显著高于不典型增生组（P＜0．01）及内异组（P＜0．01）,癌变组癌变区p53蛋白表达阳性率显著高于内异区（P＜0．05）;癌变组内异区bcl-2蛋白表达阳性率显著高于内异组（P＜0．05）,不典型增生组内异区bcl-2蛋白表达阳性率显著高于内异组（P＜0．01）。bcl-2、p53蛋白表达与绝经与否、肿瘤期别、生存期无明显相关性（P＞0．05）;癌变组癌变区p53、bcl-2蛋白表达无明显相关性（P＞0．05）。结论 p53、bcl-2的过度表达可能参与了内异症癌变的过程,p53蛋白阳性或bcl-2蛋白阳性的内异症可能是癌前病变。     

Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours

BACKGROUND: We examined the expression of apoptosis-related proteins in serous versus mucinous borderline ovarian tumours, in comparison with benign and malignant ovarian tumours. MATERIALS AND METHODS: Immunohistochemical expression of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2, bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10 mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous). RESULTS: A difference in semi-quantitative p53 expression was found between benign and borderline tumours (P = 0.01), but not between borderline and malignant tumours. Increased p21 expression was found in borderline versus benign tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P = 0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x expression was observed among the three tumour types. Higher percentage of p21 positive cells was found in serous than in mucinous borderline tumours (P < 0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No difference in p53, bax, bak, fas or bcl-x expression was observed between serous and mucinous borderline ovarian tumours. CONCLUSION: Although p53 overexpression was a common feature of both mucinous and serous borderline tumours, p21 and bcl-2 overexpression appeared specific to serous tumours.     

Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer.

Bcl-2 expression in colorectal carcinomas was studied in a series of 224 patients and the relation to p53 expression, stage and survival assessed. Bcl-2 expression was down-regulated compared with normal mucosa in 67% (151) of the cases. In 144 cases staining was positive for p53 (MAB DO7), and 41 of these 144 p53-positive cases were also bcl-2 positive (28%) compared with 32 of the remaining 80 p53-negative cases (40%). Survival was significantly worse (P = 0.01) in the p53-positive cases. Bcl-2-positive cases, including patients in all Dukes'' stages, had a slightly better prognosis which was not statistically significant. However, cases at an early stage (Dukes'' stages A and B) and with negative p53 status, had a much better prognosis if they showed bcl-2 protein expression, suggesting that the bcl-2 status itself has an effect on prognosis (P = 0.01). Neither bcl-2 nor p53 alone was correlated with stage, but when examined by both p53 and bcl-2 status a group [bcl-2(+)/p53(-)] with better prognosis was defined. The last group was significantly lower Dukes'' stage, with 26 out of 32 cases (81%) being A or B compared with 22 (11%) of the 202 remaining cases (P = 0.004). Thus, either loss of bcl-2 expression or gain of abnormal p53 expression is associated with high stage and poor prognosis. The bcl-2(+)/p53(-) phenotype is similar to that of normal mucosa, and these results suggest that such cases represent an indolent group at an early stage in the progression of colorectal cancer.