大肠肿瘤中p53和bcl-2蛋白的表达

目的：研究Ｐ５３和ｂｃｌ－２在大肠肿瘤发生中的作用。方法：应用免疫组化Ｓ－Ｐ法分别检测大肠正常、腺瘤及腺癌中Ｐ５３和ｂｃｌ－２表达。结果：大肠腺癌Ｐ５３表达率高于腺瘤组;Ｐ５３表达与大肠癌的临床病理因素无关,ｂｃｌ－２在正常粘膜基底部上皮细胞表达,在腺瘤（７７．５％）和腺（５５％）ｂｃｌ－２表达差异显著,高分化腺癌ｂｃｌ－２表达率（７３．７％）高于差分化癌（４１．２％）,在腺瘤和腺癌中ｂｃｌ－２和     

p53 protein expression in colorectal adenomas: an immunohistochemical study using an antigen retrieval system

The immunohistochemical expression of the p53 gene product was examined in 91 colorectal adenomas from patients without (group 1,50 cases) or with (group 2,41 cases) concurrent sporadic colorectal carcinoma, and in 15 additional cases of randomly selected carcinomas from group 2 patients. Immunohistochemical reactions were performed with the DO-7 monoclonal and the CM1 polyclonal antibodies, following microwave irradiation of the tissues in an antigen retrieval solution, and the proportion of the immunoreactive cells was semiquantitatively assessed. p53 protein immunoreactivity was present in 46.1% (42, of 91, i.e., 20 out of 50 of group 1 and 22 out of 41 of group 2) and 33% (30 of 91, i.e. 14 out of 50 of group 1 and 16 out of 41 of group 2) of the adenomas using DO-7 and CM1 antibody, respectively. High p53 expression (i.e. immunolabelling of more than 30% of the tumour cell nuclei) was found in 13.2% of the adenomas (12 of 91, i.e. three out of 50 of group 1 and nine out of 41 of group 2; P= 0.025 using the X² test) using the DO-7 antibody, and in 6.6% of the cases (six of 91, i.e. two out of 50 of group 1 and four out of 41 of group 2) using the CM1 antibody. In carcinomas, 80% of the cases (i.e. 12 of 15) were found to express p53 protein with both antibodies. p53 immunoreactivity in colorectal adenomas increased with the degree of dysplasia: only five (17.8%) of the 28 adenomas with mild dysplasia were found to be DO-7 positive, while all of them remained CM1 negative. From the 50 adenomas exhibiting moderate dysplasia, 28 (56%) were DO-7 positive, and 22 (44%) were CM1 positive. Finally, from the 13 adenomas with severe dysplasia, nine (69.2%) and eight (61.5%) were found to be positive with the DO-7 and the CM1 antibody, respectively. Our results indicate that an increased number of group 2 adenomas express p53 protein, when compared with group 1 adenomas, and suggest that a strong correlation exists between p53 protein expression and the degree of dysplasia in colorectal neoplasms.     

bcl-2和p53表达在结直肠癌预后评估中的价值

目的　探讨bcl 2和 p5 3表达水平与结直肠癌肿瘤生物学特征及其预后的关系。 方法　应用免疫组化S P法 ,检测93例结直肠癌标本中bcl 2与p5 3蛋白的表达 ,并与临床病理特征进行相关分析。结果　bcl 2蛋白在结直肠癌的阳性表达率为 5 7 0 % (5 3/ 93) ,与淋巴结转移呈负相关 (P <0 0 1) ,p5 3表达阳性率为 4 3% (4 0 / 93) ,与淋巴结转移无相关 (P >0 0 5 ) ,但p5 3表达阳性患者的预后差于 p5 3阴性组 (P =0 0 1)。当分析bcl 2和 p5 3联合表达时 ,Dukes分期及淋巴结转移各组间有差异 (P <0 0 5 )。其中bcl 2 (+) / p5 3(- )表达形式多见于DukesA和B期肿瘤 (4 1 0 % ,2 3/ 5 6 )。经Cox模型多因素分析结果表明 ,淋巴结转移 (P <0 0 1)和 p5 3表达 (P <0 0 1)是结直肠癌独立预后影响因素。其他指标 ,包括bcl 2和 p5 3联合表达情况等均未显示出统计学意义。结论　bcl 2和p5 3表达水平可提示结直肠癌的生物学行为 ,但bcl 2的表达与淋巴结转移状况相关不是一个单独作用的预后指标 ,而 p5 3虽与其它生物学特性关系不大 ,却是一个相对独立的结直肠癌预后指标。     

膀胱癌中p53、c—myc和bcl—2的表达及意义

目的：研究癌基因和抗癌基因蛋白产物在膀胱移行细胞癌组织中异常表达与病理分级,临床分期间关系。方法：应用免疫组化S－P法检测96例膀胱移行细胞癌中p53,c-myc和bcl-2的表达水平。结果：96例膀胱移行细胞癌中p53,c-myc和bcl-2的阳性表达率分别为60．4％,68．8％和81．3％,结果表明,p53,c-myc和bcl-2异常表达与膀胱移行细胞癌的分级和分期间差异有统计学意义。结论：p53,c-myc和bcl-2表达在膀胱癌的发生发展中起重要作用。在膀胱癌变过程中,有多种癌基因的变化。     

MIB-1 expression and iododeoxyuridine labelling in soft tissue sarcomas: an immunohistochemical study including correlations with p53, bcl-2 and histological characteristics

We investigated the relationship between immunohistochemical estimates of proliferative activity and expression of bcl-2 protein and mutant p53 protein in 23 cases of soft tissue sarcoma. Furthermore, the reproducibility of estimates of proliferative activity was analysed and correlations between the variables and with mitotic score were investigated. Proliferative activity was assessed by use of monoclonal antibody MIB-1 and staining for iododeoxyuridine (IdUrd), and evaluated in multiple, random, systematically sampled fields of vision. MIB-1 indices were higher than those of IdUrd but for each case the two values were positively correlated ( r  = 0.78). The MIB-1 index correlated positively with mitotic score ( 2P  < 0.001) and malignancy grade ( 2P  = 0.001). The intra-observer reproducibility of the MIB-1 and IdUrd indices were excellent ( r  = 0.98 and r  = 0.90, respectively). p53 expression was detected in 43% and strong bcl-2 expression was present in 57% of the studied cases. Expression of p53 and bcl-2 were not significantly correlated to proliferative activity or the histological features. We conclude, that the MIB-1 index is a reliable and reproducible estimate of proliferative activity and might improve the accuracy of conventional malignancy grading of soft tissue sarcomas. Furthermore, the results indicate that neither mutant p53 protein nor bcl-2 oncogene alone are sufficient to induce increased proliferation in these sarcomas.     

Apoptosis and proliferative activity of non-Hodgkin's lymphomas: Comparison with expression of bcl-2, p53 and c-myc proteins

In order to clarify the role of spontaneous apoptosis of non-Hodgkin's lymphomas In the growth regulation system, apoptdc Indices (Al) assessed by DNA nick end-labeling and proliferative activity, estimated In terms of Ki-67 Iabeling Indices (KI) and mitotic Indices (MI), were compared. in addition, expresslon of bcl-2, p53 and c-myc was also examIned in relation to these Indicators. For thls study, 103 Iymphoma cases were used, comprising 72 of B cell and 31 of T cell origin (42 nodal and 62 extranodal). Al, KI and MI were signiffcantty Increased in llne with bcl-2 negativity and p53 positivify, and there was no relation to the T, B cell classification or expression of c-myc. These Indicators positivety correlated overall. Posltive correlation was stricter in groups belleved to represant a good pragnostic predictive factor, such as B cell origin, bci-2(+), p53(-) and c-myc(-). Significant cross-correlation was noted only between bcl-2 wersus T, B cell classification. However, no inverse correlation between bcl-2 and p53 was evident. These results sug gest, in non-Hodgkin's lymphomas, that apoptosls plays an Important role together with proliferative activity in counterbalancing tumor volume, and is strlctty linked to bcl-2 expression, less 80 to p53 expresaion, but Independent of T, B cell classification and c-myc expression. Apoptotlc indices may be a perdlctive Indicator for prognosis simllar to proliferative activity.     

Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis,mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products

The aim of this study was to ascertain whether apoptotic counts have prognostic significance in colorectal cancer and if such counts are related to the expression of proteins implicated in cell cycle regulation. Material from a cohort of patients aged 45 years or less with colorectal carcinoma was re-examined to determine apoptotic and mitotic counts by light microscopy, in addition to assessing p53, c-myc, and bcl-2 protein status by immunohistochemistry. The apoptotic index in the 74 patients who were alive or who had died of colorectal carcinoma ranged from 1·2 per cent to 12·3 per cent and exhibited independent prognostic significance, with high counts predicting better survival (P=0·02). Mitotic counts were not related to survival, despite a close correlation with apoptosis (r=0·85). Tumours regarded as not staining with the CM1 antibody for p53 protein demonstrated higher apoptotic counts, compared with those that stained (medians 5·2 and 4·0 per cent, respectively; P=0·03), but p53 expression was found not to be related to survival. The 68 tumours which stained for c-myc appeared to exhibit higher mitotic counts than those that did not. bcl-2 was detected in only four tumours. The latter two proteins exhibited no apparent relationship to the apoptotic index or survival. Although these results indicate a potential role for apoptotic counting in prognostic prediction in colorectal tumours, this is an uncommon group of patients who exhibited some atypical features. The likelihood of a proportion of cases arising within hereditary non-polyposis colorectal cancer syndrome may limit the application of the findings to a more general population with cancer of the colon and rectum. Further work is required, including critical measurement of reproducibility and assessment of the relative impact of this parameter compared with ‘traditional’ prognostic markers. © 1997 John Wiley & Sons, Ltd.     

Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma

The present study was designed to investigate the clinical/prognostic relevance of immunohistochemical expression of p53-targeted genes mdm-2, p21WAF1 and bcl-2 alone and in combination with p53 for the indirect assessment of p53 gene status in breast cancer. 141 archival breast carcinomas were immunostained, and the putative mutational status of the p53 gene was defined in 21 of them, as a control for immunohistochemistry, using the polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis. Genetic changes of p53 correlated significantly with p53 protein overexpression (p = 0.01) but did not do so with any of the related molecules. Immunohistochemical p53 status was directly correlated with mdm-2 (p = 0.0001), p21 (p = 0.0004) and inversely with bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of prognosis, p53 only in the group of node-positive carcinomas, whereas bcl-2-/p53+ tumours revealed the worst prognosis. Mdm-2 and p21 expression was of prognostic significance neither alone nor in combination. We conclude that the detection of down-stream regulators of p53 does not increase the efficacy of immunohistochemistry in assessing the functional status of p53 in breast cancer; however, their combined analysis may help to select subgroups of patients at the extremes of risk for recurrence, or those with greater chances for survival.     

Prognostic value of immunohistochemical staining of p53, bcl-2, and Ki-67 in small cell lung cancer

Small cell lung cancer (SCLC) is one of the most fatal cancers in humans and many factors are known to be related to its poor prognosis. Immunohistochemical (IHC) stainings were done on SCLC specimens in order to investigate the prognostic value of the apoptosis-related gene expression and the tumor proliferative maker, and the relationships among these IHC results and patients clinical characteristics, chemoresponsiveness, and survival were analyzed. The medical records of 107 patients were reviewed retrospectively. IHC stainings for p53, bcl-2 and Ki-67 expressions were performed in the 66 paraffin-embedded biopsy samples. Sixty-six out of the 107 patients were evaluable for response rate and survival. The overall response rate was 75% (95% Confidence Interval=74-76%) and the median survival time was 14 months. The median survival time of limited stage was 16 months and that of extensive stage was 10 months. The prevalence of p53, bcl-2 and Ki-67 expression was 62%, 70%, and 49%, respectively. There were no correlations among the immunoreactivities of p53, bcl-2 and Ki-67 with clinical stage, chemoresponsiveness or overall survival. The clinical stage was the only prognostic factor influencing survival. The expression rates of p53, bcl-2, and Ki-67 were relatively high in SCLC without any prognostic significance. The exact clinical role of these markers should be defined through further investigations.     

bcl-2 and p53 protein expression in follicular lymphoma

Recent studies have shown bcl-2 to be regulated by p53. Other studies have suggested an inverse relationship between p53 and bcl-2 protein expression in breast and colonic cancers and in a variety of subtypes of non-Hodgkin's lymphoma. This study investigates the relationship between bcl-2 and p53 protein expression and the correlation between these findings and the grade and cell type of follicular lymphomas according to the REAL classification. Paraffin-embedded nodal follicular lymphomas (n=37) were subjected to bcl-2 and p53 immunohistochemistry on tissue sections using a three-step ABC system. Positive immunostaining for both oncoproteins was scored using a three-tiered scale: +, <10 per cent cells; ++, 10–50 per cent cells; and +++, >50 per cent cells (<10 per cent was used as a cut-off to define negative tumours). Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1=6 per cent (1/16); grade 2=48 per cent (10/21); grade 3=100 per cent (6/6). Five cases comprised varying combinations of grades. This latter finding suggests a role for p53 mutation in the progression/transformation of follicular lymphoma. The mechanism, however, differs from that suggested in breast and colonic cancers, since an inverse relationship between bcl-2 and p53 was not demonstrated in the present study. © 1997 John Wiley & Sons, Ltd.     

Correlation of p53 protein expression with apoptotic incidence in colorectal neoplasia

The wild-type p53 gene suppresses cell proliferation and induces apoptosis when it is transfected into human colon cancer cell lines. Therefore, mutation of the p53 gene, which correlates closely with p53 protein overexpression, would be predicted to activate cell proliferation and limit apoptosis. We tested this hypothesis by correlating p53 protein expression with cell proliferation and apoptosis in 70 neoplasms (29 adenomas and 41 carcinomas) using p53 and Ki-67 immunohistochemical staining and DNA nick end labelling. The p53 immunoreactivity was independent of the Ki-67 positivity. The apoptotic incidence was less frequent (P<0.005) in tumours with diffuse p53 protein overexpression than in those with the sporadic overexpression, defined as p53 staining of isolated or scattered expression. In addition, apoptotic incidence only correlated directly (P<0.05) with Ki-67 positivity in tumours with sporadic p53-protein expression. These results indicate that p53 protein that is expressed sporadically in colorectal neoplasms is probably wild-type protein and induces apoptosis in response to active cell proliferation. In contrast, diffusely overexpressed p53 protein in colorectal neoplasms is probably mutant and correlates with a reduction in apoptotic cell death independently of cell proliferation.     

Relationship of Fas,FasL, p53 and bcl-2 expression in human non-small cell lung carcinomas

Objective: Lack of surface Fas expression is a main route for apoptotic resistance which is considered an important mechanism of tumorigenesis and tumor progression. Fas and FasL expression in 110 non-small cell lung carcinomas (NSCLCs) were investigated to evaluate their roles in pulmonary carcinogenesis and to examine the clinicopathologic significance of Fas expression with its relationship with p53 and bcl-2 over- expression. Methods: Immunohistochemical analysis using tissue microarray demonstrated that a large proportion of NSCLC patients (60%) showed lack of membranous Fas expression. The Fas-negative cases revealed the significantly lower survival rate than Fas-positive ones. Also, the loss of Fas receptor expression was found more frequently in advanced stage and higher nodal status. FasL protein was increased in most NSCLCs (89%) compared to normal lungs. Results: p53 and bcl-2 overexpression showed no association with Fas expression. Conclusively, reduced membranous Fas expression as a mechanism of apoptotic resistance is considered to play an important part of the pulmonary carcinogenesis, which may predict poor survival and have a negative prognostic influence. Conclusion: Increased FasL expression is thought to be a basis for the immune evasion in NSCLCs. The rare bcl-2 overexpression suggests that this anti-apoptotic protein is unlikely to play a role in the apoptotic resistance of NSCLCs.     

Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression

Tissue microarray technology enables the analysis of hundreds of specimens by arranging numerous 0.6-mm tissue core biopsy specimens into a single paraffin block. Validation studies are necessary to evaluate the representativeness of small disks taken from the original tissue. We validated the tissue microarray technology in colorectal carcinoma by analyzing the immunohistochemical expression of proteins involved in the two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors, hMLH1 and hMSH2 proteins for microsatellite instability (MSI) tumors. We compared in 30 colorectal carcinomas (15 MSI^– and 15 MSI⁺), 8 microarrays disks, and the whole section of the block from which they were derived. Tumoral tissue was present in 95.7% of the microarray disks. The analysis of three disks per case was comparable to the analysis of the whole section in 99.6% (p53), 98.8% (hMLH1), and 99.2% (hMSH2) of cases. In the second part we applied the tissue microarray technology to 263 consecutive cases of colorectal carcinoma, sampled by three cores. We showed that 48.5% overexpressed p53 and 8.7% lost hMLH1 or hMSH2. Tissue microarray technology, validated in colorectal carcinoma, appears as a useful research tool for rapid analysis of the clinical interest of molecular alterations.     

p53 and bcl-2 protein expression in non-small-cell lung carcinoma

The diagnostic significance of p53 and bcl-2 proteins in epithelial non–small-cell lung cancers was examined, and the relationship between these proteins expression and other disease parameters, including stage of the disease and tumor differentiation, were studied. We analyzed p53 and bcl-2 proteins expression in 60 imprint smears of freshly resected lung tumors (37 squamous and 23 adenocarcinomas) using the immunocytochemical technique. There were seven patients with stage I disease, 24 with stage II, 23 with stage IIIa, and six with stage IIIb disease, according to the International Staging System classification. Sixteen of the tumors were bcl-2 positive and 25 were p53 positive. Twenty tumors were negative for both bcl-2 and p53 (33.3%). Statistical analysis showed no association between the incidence of p53 or bcl-2 positivity. Adenocarcinoma or squamous carcinoma analysis showed significant associations between p53 positivity and poor differentiation and advanced disease stage as well as bcl-2 and early disease stage and well-differentiated tumors. There was also an association between the stage of the disease and the degree of differentiation of the tumors. In conclusion, bcl-2 positivity must be considered a good prognostic sign. On the other hand, p53 positivity seems to indicate, even in tumors at a relatively early stage, that a serious aggressive tumor which will not be easily eradicated is present. Diagn. Cytopathol. 1998;19:255–259. © 1998 Wiley-Liss, Inc.     

癌基因c-erbB2、c-myc和抑癌基因p16、p53在口腔鳞癌中的蛋白表达及其协同作用

目的：探讨癌基因c—erbB2、c-myc和抑癌基因p16、p53在口腔鳞癌(OSOC)中的蛋白表达及其协同作用。方法：用免疫组化结合图像分析对口腔鳞癌中4种基因的蛋白表达进行定性、定位、定量研究。结果：口腔鳞癌中c—erbB2、c—myc、p16和p53的蛋白表达阳性率依次为46．67％、60％、86．67％和63。33％。肿瘤部位不同,erbB2蛋白表达有显著性差异;腭癌和口底癌中的erbB2蛋白表达都明显高于唇癌和牙龈癌中的erbB2表达。c-myc蛋白表达与p16蛋白表达之间具有显著性相关。结论：以上4种基因的蛋白表达增高在口腔鳞癌发生发展中具有重要作用,c—erbB2蛋白过表达在腭癌和牙龈癌中具有更重要的意义;c—myc和p16蛋白表达间具有一定的内在联系。     

Prognostic value of p53, bcl-2, and c-erbB-2 protein expression in phaeochromocytomas

Many studies have tried to discriminate malignant from benign phaeochromocytomas, but until now no widely accepted histological, immunohistochemical, or molecular methods have been available. In this study of 29 malignant and 85 benign phaeochromocytomas from 102 patients, immunohistochemistry was performed with antibodies to the tumour suppressor gene product p53 and the proto-oncogene products bcl-2 and c-erbB-2, using the avidin–biotin complex method. Malignant phaeochromocytomas showed a statistically significant higher frequency of p53 (p=0·042) and bcl-2 (p=0·037) protein expression than their benign counterparts. The combination of both markers showed an even higher significance (p=0·004), to which both markers contributed equally. Overexpression of c-erbB-2 was associated with the occurrence of familial phaeochromocytomas (p=0·001), but no difference was found between benign and malignant cases. In conclusion, p53, bcl-2, and c-erbB-2 all appear to be involved in the pathogenesis of a proportion of phaeochromocytomas. Immunoreactivity to p53 and bcl-2 proteins may help to predict the clinical behaviour of phaeochromocytomas. Copyright © 1999 John Wiley & Sons, Ltd.     

人甲状腺髓样癌内凋亡细胞检测和bcl-2、p53及Ki-67的免疫组化研究

目的：检测甲状腺髓样癌内凋亡细胞、ｂｃｌ－２、ｐ５３和Ｋｉ－６７，探讨其与患者的预后关系。方法：在２１例甲状腺髓样癌内，用ＤＮＡ末端标记方法检测凋亡细胞和用免疫组织化学技术检测ｂｃｌ－２、ｐ５３及Ｋｉ－６７的表达。结果：在２１例甲状腺髓样癌标本中，凋亡细胞ｂｃｌ－２、ｐ５３和Ｋｉ－６７的检出率分别为８１％，１００％，６２％和７１％。ｂｃｌ－２阳性物质位于肿瘤细胞的胞浆内，少数病例则位于膜上。ｐ５３蛋白阳性主要位于胞核内，少数病例也同时见于胞浆内。Ｋｉ－６７抗原主要位于肿瘤细胞核内。本研究结果表明，ｂｃｌ－２和肿瘤细胞凋亡之间有密切关系（Ｐ＜０．０１）。ｂｃｌ－２阳性细胞检出率较高的病例，凋亡细胞检出率则较低；反之，凋亡细胞检出率则较高。ｐ５３和Ｋｉ－６７阳性细胞检出率和细胞凋亡无相关性（Ｐ＞０．０５）。结论：ｂｃｌ－２具有抑制细胞凋亡的作用。上述各因素检测结果与患者存活率无统计学意义。ｂｃｌ－２肿瘤蛋白在甲状腺髓样癌中高表达，可作为该肿瘤的一个新的标记物，对预后的判断可能也有一定的意义     

EGFR and p53 expression and proliferative activity in parathyroid adenomas; an immunohistochemical study

EGFR (epidermal growth factor receptor), p53, and proliferative markers provide some clues as to the formation of several tumours. In this study the mechanism of the genesis of parathyroid adenomas was investigated using immunohistochemistry. Sections of parathyroid adenomas from 12 cases were stained using PCNA (proliferating cell nuclear antigen), EGFR, and p53 immunohistochemistry. Correlations between PCNA LI (labelling index), EGFR expression, p53 expression, age, serum parathormone, Ca and P levels, and tumour diameter were investigated. PCNA LI was 45.8+/-33.1 (mean+/-standard deviation) and all the cases were somewhat positive. Five cases (41.67 %) were EGFR positive. Maximum 10 % of the cells were positive in these cases. All the cases were p53 negative. There was a correlation between PCNA LI and serum parathormone level (r=0.607, p=0.036). According to these results, parathormone synthesis is high when the proliferative activity of parathyroid adenoma is high. Four of the five EGFR-positive patients were below 35 years of age. These data may indicate that formation of parathyroid adenoma in young patients is related to a mechanism involving EGFR. Absence of p53 expression suggests that p53 mutation is not a common component of parathyroid adenomas.     

Epithelial neoplasms of the appendix and colorectum: an analysis of cell proliferation,apoptosis, and expression of p53, CD44, bcl-2

CONTEXT: Carcinomas of the appendix are usually well-differentiated mucinous adenocarcinomas that tend to produce pseudomyxoma peritonei and do not show metastatic spread until late in the disease process. In contrast, adenocarcinomas of the colon and rectum rarely result in pseudomyxoma peritonei and frequently metastasize, even if mucinous and well differentiated. These differences in behavior may be reflected by differences at the molecular level. OBJECTIVES: To examine adenocarcinomas and their precursor lesions (adenomas) of the appendix and colorectum and to determine whether differences exist in the numbers of proliferating and apoptotic cells or in expression of p53, bcl-2, and the standard form of CD44 (CD44s). DESIGN: Retrospective analysis of surgical specimens. SETTING: Multicenter study. PATIENTS: Individuals treated surgically for tumors of the appendix or colorectum. INTERVENTIONS: Sections were cut from formalin-fixed surgical specimens and immunohistochemical tests were performed for Ki-67 (as a marker of proliferating cells), M30 (as a marker of apoptotic cells), p53, CD44s, and bcl-2. MAIN OUTCOME MEASURES: Expression of Ki-67, M30, p53, CD44s, and bcl-2 in tumor cells. RESULTS: The appendiceal adenomas showed significantly lower Ki-67 counts, p53 expression, and bcl-2 expression. When compared with adenocarcinomas of the colorectum in general (mucinous and nonmucinous), the appendiceal adenocarcinomas showed significantly lower Ki-67 counts, M30 counts, and CD44s expression. However, when the analysis was confined to well-differentiated mucinous adenocarcinomas, only the M30 count was significantly different. CONCLUSIONS: The lower proliferative and apoptotic activity of appendiceal carcinomas and the lower CD44s expression are in keeping with their more indolent behavior compared with adenocarcinomas of the colorectum. However, when only the subset of well-differentiated mucinous adenocarcinomas was compared, only the apoptotic activity was different, suggesting that the other differences were related to the morphologic structure of the lesions.