Immunohistochemical expression of CK20, p53, and Ki-67 as objective markers of urothelial dysplasia.

Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Distinguishing CIS and dysplasia from reactive atypia is often difficult on the basis of histological features alone. Cytokeratin 20 (CK20), p53, and Ki-67 are related either to neoplastic change or prognosis in urothelial proliferations. The objective of the present study was to establish the immunohistochemical pattern of these three antibodies in urothelial dysplasia and CIS. Three groups of patients were evaluated: 40 nonneoplastic urothelial samples, 50 cases with histologically incontrovertible CIS, and 30 samples with nonconclusive atypical changes (atypia of unknown significance). Monoclonal antibodies (MoAb) against CK20, p53, and Ki-67 (MIB-1) were used on paraffin-embedded samples. Nonneoplastic urothelium showed no reactivity to CK20 except for umbrella cells; p53 and Ki-67 were negative or weakly positive in <10% of basal cells. In the CIS group, 42% showed positivity for all three MoAb; 44%, for two; and 14%, only for one. CK20 was positive through the full thickness of the urothelium in 72% of cases, p53 was positive in 80% of cases, and Ki-67, in 94% of cases. In the third group, the suspected dysplastic cells showed strong positivity in scattered cells through the epithelium in 75% of cases. Aberrant CK20 expression in urothelial cells plus overexpression of p53 and Ki-67 are indicators of dysplastic change in urothelial mucosa. Thus, immunohistochemistry is a useful tool to confirm the diagnosis of CIS and could be helpful to distinguish dysplastic changes from reactive atypia.     

Thioredoxin, a putative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival

Human thioredoxin is a putative oncogene that may confer both a growth and survival advantage to tumor cells. Overexpressed thioredoxin mRNA has been found in both primary human lung and colorectal cancers. To determine the intratumor distribution and amount of thioredoxin protein in human primary carcinomas, we developed an immunohistochemical assay for thioredoxin in paraffin-embedded tissue. We then studied 10 patients with primary high-risk gastric carcinoma. To further relate thioredoxin protein overexpression to cell death and survival, we used a paraffin-based in situ end-labeling (ISEL) assay. To delineate proliferation, we used the nuclear proliferation antigen detected by Ki-67. In this survey, we found that thioredoxin was localized to tumor cells and overexpressed compared with normal gastric mucosa in 8 of 10 gastric carcinomas. The thioredoxin was found at high levels in 5 of the 8 overexpressing carcinomas. The overexpression of thioredoxin was typically found in both a nuclear and cytoplasmic location in the neoplastic cells. There was a significant positive correlation (P = .0061) with cancer cell proliferation measured by Ki-67. There was a significant negative correlation (P = .0001) with DNA damage measured by the ISEL assay, suggesting decreased apoptosis and increased carcinoma cell survival. Thus, human primary gastric tumors that are highly expressive of thioredoxin have both a higher proliferative rate and a higher survival rate than tumors that do not express thioredoxin. With these newly developed assays in hand, it is now feasible to question whether this thioredoxin-related combined growth and survival advantage translates into poor clinical outcome.     

Apoptosis and expression of bcl-2 protein in invasive ductal adenocarcinoma of the pancreas

Apoptosis plays a central role in the development and/or progression of cancer. There are several methods for detection of apoptotic cells in tissue sections including light and electron microscopy, in situ nick end-labeling (ISEL), TdT-mediated dUTP nick-end labeling (TUNEL) and immunohistochemical detection of proteins associated with apoptosis. Apoptosis was assessed by the monoclonal antibody M30 CytoDEATH (M30), which is specific for neo-epitope in cytokeratin 18 that becomes available at an early caspase cleavage during apoptosis. Expression of bcl-2 protein was evaluated, because bcl-2 protein plays an important role in the regulation of apoptosis. Twenty-six invasive ductal adenocarcinomas of the pancreas were studied immunohistochemically with antibodies M30 and bcl-2. The mean apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells number) was 2.75%. High AI (> 10%) was observed in 4 cases of the 26 pancreatic carcinomas (15%). Protein bcl-2 was expressed in 3 cases (11.5%). The AI did not correlate with the expression of protein bcl-2. In conclusion, the detection of neo-epitope in cytokeratin 18 by monoclonal antibody M30 can be used for quantification of apoptotic cells with immunohistochemical techniques in tissue sections. It is a new approach to evaluate apoptosis in pancreatic carcinomas. The low positivity of bcl-2 expression in pancreatic adenocarcinomas suggests that bcl-2 protein does not play a central role in pancreatic tumorigenesis and cancer progression.     

Ki-67、早期凋亡相关蛋白M30在子宫内膜癌的表达及其与预后的关系

目的　探讨子宫内膜癌增殖抗原Ki 6 7及早期凋亡相关蛋白M 30 (M30CytoDEATH ,细胞角蛋白 18)的表达与其生物学行为间的关系。方法　采用免疫组织化学链霉素抗生物素蛋白 过氧化物酶 (SP)法 ,分别检测了 79例子宫内膜癌Ki 6 7及M30蛋白的表达情况。结果　 79例子宫内膜癌中 ,不同病理学分级间Ki 6 7平均指数分别为 :G1:2 0 4 8± 14 86 ;G2 :2 4 12± 14 4 2 ;G3:38 84± 11 88。不同临床分期间Ki 6 7平均指数分别为 :Ⅰ期 :2 0 6 5± 13 5 6 ;Ⅱ期 :2 6 92± 14 71;Ⅲ期 :35 14± 14 70。不同病理学分级间M30蛋白平均指数分别为 :G1:1 0 3± 1 4 2 ;G2 :1 0 3± 1 6 4 ;G3:1 94± 1 2 0。不同临床分期间M30蛋白平均指数分别为 :Ⅰ期 :0 30± 0 5 8;Ⅱ期 :1 6 6± 1 74 ;Ⅲ期 :2 0 7± 1 6 2。研究结果还显示子宫内膜癌M30指数随Ki 6 7指数增高而增高 ,它们之间呈显著正相关。生存分析表明 ,Ki 6 7指数≥ 30、M30指数≥ 2的患者比Ki 6 7指数≤ 10、M 30指数≤ 1的患者生存率显著降低。结论　Ki 6 7指数、M 30指数越高 ,子宫内膜癌生物学行为越差 ,患者预后也越差。Ki 6 7指数、M 30指数较高的患者 ,生存率显著降低。高分化子宫内膜癌 (G1)中 ,Ki 6 7指数≥30、M30指数≥ 2者可能提示患者预     

Immunohistochemical study of DNA topoisomerase I, p53, and Ki-67 in uterine carcinosarcomas

Uterine carcinosarcomas (UCs) are highly aggressive neoplasms for which no effective adjuvant therapy has been established. The aim of this study was to test potential indicators of UC sensitivity to topoisomerase I (topo I)-targeted drugs. Laboratory studies have shown that the cellular response to topo I-targeted drugs is dependent on topo I expression, DNA replication rate, and activity of the apoptotic pathway. Therefore, this study investigated expression of topo I, a proliferation marker Ki-67, and the apoptosis initiator p53 in 20 cases of UC. Formalin-fixed paraffin-embedded tissue sections were immunostained with monoclonal antibodies against topo I, Ki-67, and p53. The hospital records of all 20 patients with UC were reviewed. Twelve (60%) of 20 cases showed increased expression of topo I. Staining for Ki-67 showed elevated expression in 15 (75%) of 20 cases. Fourteen cases (70%) showed positive staining for p53 in more than 20% of the tumor cells. However, analysis of the relationship between immunohistochemical results and clinical parameters revealed no correlations with topo I expression. There were no significant correlations between the expression of topo I and Ki-67 (P = .704), or topo I and p53 (P = .465). Significantly increased expression of topo I, Ki-67, and p53 in UC tumor cells suggests sensitivity to topo I-targeted drug treatment.     

Prognostic significance of apoptosis in synovial sarcoma: correlation with clinicopathologic parameters, cell proliferative activity, and expression of apoptosis-related proteins.

bcl-2 overexpression in synovial sarcomas has been recently reported. Although it is widely known that bcl-2 suppresses apoptosis in various cells, there are no studies that have examined the significance of apoptosis in synovial sarcoma. In the present study, we visualized apoptotic tumor cells by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of apoptosis was analyzed in relation to several clinicopathologic parameters, cell proliferative activity, and immunohistochemical expression of apoptosis-related proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index (MI) (? = 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (? = 0.52, P = 0.0005). There was a highly significant association between high TUNEL-I value (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and were negative or only sporadically positive for Fas, Fas ligand, p53, and p21 (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in primary synovial sarcoma was considered to be an indicator of poor prognosis. In addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis-regulating mechanisms, including the bcl-2 family.     

Proliferation and apoptosis in normal bitch mammary tissues in relation to progesterone level

The objective of this study was to investigate the proliferating activity and apoptosis in canine normal mammary tissues in different cycle stages. Mammary tissues were collected from five beagle bitches at six different estrous stages: anestrus, proestrus, estrus, early diestrus, mid diestrus, and late diestrus. The expression of Ki-67 protein and apoptotic bodies was evaluated by avidin–biotin–peroxidase complex (ABC) method and TUNEL assay, respectively. Percentage of Ki-67 positive cells and apoptotic bodies was calculated. The significant highest percentage of Ki-67 positive cells and apoptotic bodies was observed at mid diestrus. Positive correlation was found mainly in the alveolar epithelium between progesterone levels and percentage of Ki-67 positive cells, as well as between progesterone levels and apoptosis. In conclusion, the results from the present study suggested that progesterone may influence on proliferation and apoptosis in canine mammary tissue.     

Developmental patterns of Ki-67, bcl-2 and caspase-3 proteins expression in the human upper jaw

The distribution of the Ki-67, bcl-2 and caspase-3 proteins was immunohistochemically analyzed in the developing human upper jaw (5th-10th gestational weeks).During this period, proliferative activity gradually decreased from higher levels at the earliest stages (50-52%) to lower levels, both in the jaw ectomesenchyme and in the epithelium. The highest expression of bcl-2 protein was found in the epithelium and ectomesenchyme of areas displaying lower rates of cell proliferation. High levels of caspase-3 protein were detected during the earliest stages of jaw development, indicating an important role for apoptosis in morphogenesis of early derivatives of the maxillary prominences. The number of Ki-67, bcl-2 and caspase-3 positive cells changed in a temporally and spatially restricted manner, coincidently with upper jaw differentiation. While apoptosis might control cell number, bcl-2 could act in suppression of apoptosis and enhancement of cell differentiation. A fine balance between cell proliferation (Ki-67), death (caspase-3) and cell survival (bcl-2) characterized early human upper jaw development. A rise in the number of apoptotic cells always temporally coincided with the decrease in number of surviving bcl-2 positive cells within the palatal region. Therefore, the upper jaw development seems to be controlled by the precisely defined expression of genes for proliferation, apoptosis and cell survival.     

Role of fragile histidine triad protein expression in pathogenesis of malignant pleural mesothelioma

AIM:To investigate the relationship of fragile histidine triad (FHIT) and Ki-67 expression with clinicopathological variables of patients with malignant pleural mesothelioma (MPM). METHODS: Formalin-fixed, paraffin-embedded tissue sections of 30 asbestos induced MPM (epithelial and biphasic) patients were examined for FHIT and Ki-67 expression using immunohistochemical techniques and results were compared with clinicopathological variables. RESULTS: Immunohistochemical study results were as follows: 12 (40%) cases showed low FHIT expression and 18 (60%) showed high expression. There was no significant relationship between FHIT and age, gender or histological subtypes (p > 0.05). Ki-67 expression was 'low' in 13 (43.3%) cases and 'high' in 17 (56.7%) cases. No correlation could be demonstrated between Ki-67 expression and age, gender or histological subtypes (p > 0.05). No significant association was observed between FHIT and Ki-67 expression in MPM. CONCLUSION: The results support the role of FHIT as a tumour suppressor gene in asbestos induced MPM. There is no significant correlation between FHIT and cell proliferation marker expressions in malignant pleural mesothelioma. Therefore, it can be concluded that loss of FHIT does not interfere with tumour proliferation. This can be accepted as evidence for an early role of FHIT loss in carcinogenesis; however, it needs to be strengthened by further studies.     

Activation of T cells in the blood of patients with acute malaria: proliferative activity as indicated by Ki-67 expression

The expression of the proliferation-associated nuclear antigen Ki-67 in peripheral blood mononuclear cells was studied in 30 patients with acute malarial illness and 11 healthy controls from Addis Ababa or Nazareth in Ethiopia. Seventeen patients had Plasmodium falciparum infections and 13 had Plasmodium vivax. Two-colour immunoenzymatic staining was developed in order to simultaneously detect the expression of the nuclear antigen Ki-67 and determine the surface phenotype of the cell. The median percentage of proliferating, Ki-67 positive lymphocytes was significantly higher in patients with acute P. falciparum (11.8%) and P. vivax (15.6%) illnesses compared to the controls (4.3%). The majority of Ki-67 positive cells were T cells (CD3+) while the relative increase of Ki-67 expressing cells was similar for both the CD4+ and CD8+ T-cell subsets. Our data show an increased number of activated cells driven to proliferation in the peripheral blood of patients during acute malaria illness.     

弥漫性大B细胞淋巴瘤中AID蛋白的表达及意义

目的研究活化诱导胞苷脱氨酶(activation-induced cytidine deaminase,AID)在弥漫性大B细胞淋巴瘤(diffuse large Bcell lymphoma,DLBCL)中的表达,探讨其与DLBCL的临床病理特征、免疫组化亚组及预后的关系。方法采用组织芯片免疫组化法检测101例DLBCL中AID、CD10、BCL-6、MUM1、Ki-67的表达,免疫组化双重染色检测AID与CD20、Ki-67的共定位表达。结果 AID在DLBCL的肿瘤性B细胞中阳性表达率为26.7%。101例DLBCL中,AID阳性表达率在年龄≥60岁患者中明显高于<60岁的患者(P<0.05),AID的表达与患者性别、病变部位、形态学变异型、免疫组化亚组无关(P>0.05)。DLBCL中,AID的表达与B细胞分化标记物CD10、BCL-6和MUM1的表达无相关性(P>0.05),与Ki-67增殖指数(Ki-67>50%)呈正相关(P<0.05)。生存分析表明,AID阳性表达者的5年生存率明显低于AID阴性表达者,两者之间的差异具有统计学意义(P=0.042)。结论 AID的阳性表达与DLBCL的不良预后...     

In situ localization of S-phase-specific histone (H3) mRNA in Bowen's disease

PCNA and Ki-67 immunohistochemistry has been used to assess cell proliferation in place of tritiated thymidine or BrdU labeling of S-phase cells. Recently, it has been possible to reliably demonstrate histone H3 mRNA by in situ hybridization in formalin-fixed and paraffin-embedded tissue sections. We have compared this new proliferation marker with Ki-67 and PCNA with regard to distribution of positive cells and labeling indices (LI%) for 22 cases of Bowen's disease. In normal skin, Ki-67-IHC positive cells and histone mRNA positive cells were observed in the basal and suprabasal layers of the epidermis. In Bowen's disease, positive cells with each marker were more frequent in upper neoplastic epidermis than in suprabasal layers, and the average LI%s were markedly elevated with all markers, the scores decreasing in the following order: PCNA-IHC, Ki-67-IHC and H3mRNA-ISH. However, the results of double staining demonstrated that S-phase cells do not necessarily show exactly the same distributions as with PCNA and Ki-67-IHC labeling. H3mRNA-ISH showed three different degrees of reaction with significantly different LI%s, whereas PCNA and Ki-67 LI% did not vary essentially in the same areas. These results strongly suggest that Bowen's disease, which is well known as a low-grade neoplastic state with malignant potential, also demonstrates clear intratumoral heterogeneity of S-phase cells using the H3mRNA-ISH method.     

Increased tissue immunoexpression of YKL-40 protein in high grade serous ovarian cancers

YKL-40 is a glycoprotein secreted by numerous human cells, such as cartilage, synovial, and endothelial cells. The biological role of YKL-40 has not yet been fully unveiled, however, its participation is perceived in angiogenesis, growth, proliferation, differentiation, and remodeling processes. The primary goal of our study was to evaluate possible differences in tissue immunoexpression of YKL-40, assumed between high grade and low-grade ovarian cancers and between the above-mentioned cancer types and benign lesions. Another purpose was to find out whether immunoexpression of the studied protein could correlate with the tumor proliferation process, evaluated by Ki-67 immunoexpression.The analysis comprised 45 women, diagnosed and treated for epithelial ovarian tumors at the Medical University of Lodz between 1997 and 2002. YKL-40 protein immunoexpression was semiquantitatively assessed, whereas immunoexpression of Ki-67 was evaluated using a computer image analysis system. Significantly higher immunoexpression values of both examined proteins were observed in high-grade serous ovarian cancers vs. low-grade and benign tumors. Moreover, a significant positive correlation was identified between the immunoexpressions of YKL-40 and Ki-67 proteins in the studied groups of tumors.In conclusion, the obtained data suggest an overt prominence of TKL-40 tissue immunoexpression of YKL-40 in high-grade serous ovarian tumors, which could then be approached as a helpful, additional marker to identify more aggressive ovarian cancers.     

Induction of proliferating cell nuclear antigen and Ki-67 expression by cytomegalovirus infection

With the goal of facilitating viral reproduction, cytomegalovirus (CMV) induces changes in the host cell replication machinery. Very little information is available, however, on the effects brought about by CMV on proliferating cell nuclear antigen (PCNA) and Ki-67 expression in infected cells. Fifty-five paraffin-embedded tissue samples (43 gastrointestinal, 10 skin, and 2 kidney biopsies) with both histological and immunohistochemical evidence of CMV infection were investigated for PCNA and Ki-67 expression by the avidin– biotin–peroxidase method. Of the 55 cases studied, 47 were positive for PCNA and 46 for Ki-67. PCNA and Ki-67 immunostaining was more striking in CMV-immunoreactive, inclusion-free cell nuclei, whereas cell nuclei exhibiting well-developed CMV inclusions either showed a weak peripheral signal for both proliferation markers, or were completely negative. Enhanced PCNA and Ki-67 expression appears to be among the changes induced by CMV infection in host cells. Moreover, this induction seems to reach its peak during the earlier phases of CMV infection and abate as the infection proceeds to its inclusion-forming phases, when a sufficiently high viral load would have been attained. © 1998 John Wiley & Sons, Ltd.     

Ki-67 and caspase expression in breast carcinoma: does variance in locational sampling exist?

Ki-67 and caspase indices are two very important prognostic variables for breast cancer. The aim of this study was to compare the immunoexpressions of these two prognostic variables at the center, the periphery of the tumor in comparison with each other, and additional parameters in 53 breast cancer specimens. It has been shown that the increase of caspase immunoexpression either at the periphery or the center of the tumor correlated with the increase of Ki-67 immunoexpression at the same areas. There was no statistically significant difference between caspase and Ki-67 immunoexpression at the center or the periphery of the tumor. No statistically significant correlation was found between immunoexpressions of caspase and Ki-67 with the tumor grade, stage, lymph node metastasis, lymphovascular or perineural invasion. The two very important prognostic variables of breast cancer (caspase and Ki-67) were evenly distributed in the center and the periphery of the tumor. It is evident that there is no need for a specific locational sampling when these two variables are considered. In accordance with this information, the differences in sampling due to observer diversity may be prevented.     

Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome.

The present study analysed by immunohistochemistry the protein level of cyclin A and Ki-67 in a panel of paraffin-embedded tissue obtained from 172 primary (110 superficial and 62 nodular) and 73 metastatic melanomas, and ten benign naevi. Since cyclin A exists in the same quaternary complex in the S-phase of the cell cycle as the cdk inhibitor p21WAF1/CIP1, the levels of the two proteins were compared. Cyclin A and Ki-67 were heterogeneously expressed in the malignant tumours, whereas in benign naevi, only rare positive cells were detected. In superficial spreading melanomas, the cyclin A level was related to tumour thickness, with less expression in thinner lesions (p<0.00001), and to Ki-67 (p<0.00001) and p21WAF1/CIP1 (p=0.01) scores. Multivariate analysis showed that in addition to the depth of the primary tumour, the protein level of cyclin A was an independent indicator of relapse-free period (thickness, p<0.00001; cyclin A, p=0.0003). In contrast, in nodular melanoma, the cyclin A level was associated with Ki-67 expression, but neither cyclin A nor Ki-67 was related to tumour thickness (cyclin A, p=0.06; Ki-67, p=0.61) and neither had any impact on relapse-free (cyclin A, p=0.64; Ki-67, p=0.32) or overall (cyclinA, p=0.94; Ki-67, p=0.45) survival. In conclusion, the results indicate that cyclin A is a strong prognostic factor for patients with superficial spreading melanomas. In nodular melanomas, the proliferation rate seems to have little impact on disease progression.     

DNA topoisomerase II-alpha immunoreactivity as a marker of tumor aggressiveness in invasive breast cancer.

OBJECTIVE: The nuclear enzyme DNA topoisomerase (topo) II breaks and rejoins DNA strands; its isoform topo IIalpha is associated with active cell proliferation of mammalian cells. The aim of this study was to examine the relationship between the expression of topo IIalpha and biological behavior markers in breast cancer. METHODS: Formalin-fixed, paraffin-embedded tissue from 88 samples of infiltrating breast cancer was immunohistochemically stained for topo IIalpha. For each case, a topo IIalpha index was determined by image analysis. Similar indexes were available for Ki-67 protein, a known cell proliferation marker, and p53, bcl-2 and c-erbB-2 oncoproteins. Each case had been staged and graded and the patients had been followed up for a mean period of 61.62 months. RESULTS: Elevated topo IIalpha immunopositivity (in >10% of malignant nuclei) was detected in 22 tumors, and this immunostatus was statistically associated with poor nuclear differentiation, absence of steroid hormone receptors, high Ki-67 immunoexpression, p53 protein accumulation and c-erbB-2 protein overexpression. Topo IIalpha expression was not linked with disease extent (stage or lymph node status). Neither proliferation marker (topo IIalpha or Ki-67) had any significant influence on the patients' recurrence-free survival. CONCLUSION: From the above results, we conclude that topo IIalpha overexpression appears to be linked with cellular dedifferentiation and potentially aggressive tumor phenotype in invasive breast cancer.     

Apoptosis in breast carcinoma

Apoptosis may play a major role in determining tumor growth and aggressiveness. The aim of this study was to examine the relationship between apoptosis, expression of bcl-2 and p53 proteins, proliferation index, and other clinicopathological features of breast carcinoma. Sixty-five formalin-fixed paraffin-embedded tissue sections from invasive ductal breast carcinomas were studied for the presence of apoptosis by the terminaldeoxynucleotidyl-transferase-mediated dUTP-FITC nick end-labeling (TUNEL) method. Immunohistochemical methods were also used to determine the expression of estrogen receptor, Ki67, bcl-2 and p53 proteins. The number of apoptotic cells ranged from 2.0 to 236.0/10HPF (mean 36.26, median 28.0). The observation of 30 apoptotic cells/10HPF was more common in tumors > 3 cm, of histological grade III, with a high mitotic index, Ki67 index > or = 300, and p53 positivity; however, statistical significance was found only for the histological grade. Grade I and III tumors displayed an inverse association between the apoptotic index and bcl-2 and p53 protein expressions; grade I tumors frequently expressed bcl-2 (19/28), lacked p53 (20/28), and presented a low number of apoptotic cells (18/28), whereas grade III tumors tended to express p53 (12/17), lacked bcl-2 (13/17), and displayed a high number of apoptotic cells/10HPF (12/17). Multivariate analysis for survival revealed that estrogen receptors and apoptosis were independent variables. These data suggest that apoptosis, rather than proliferation index or expression of bcl-2 or p53 proteins, is an independent factor for the prognosis of survival.     

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.     

乳腺癌组织Survivin和Ki-67的表达情况及其临床意义

目的：探讨乳腺癌与Survivin、Ki-67的相关性,以及Survivin、Ki-67检测的临床意义。方法：采用免疫组化法研究Survivin、Ki-67在乳腺癌中的表达情况。结果：36例乳腺癌患者有28例（77.8%）Survivin表达阳性,对照组30例中只有1例（3.3%）Survivin表达阳性,Survivin诊断乳腺癌的敏感性为77.8%,特异性为96.7%。36例乳腺癌患者有26例（72.2%）Ki-67表达阳性,对照组30例中无1例Ki-67表达阳性,Ki-67诊断乳腺癌的敏感性为72.2%,特异性为100%。36例乳腺癌患者中Survivin与Ki-67的表达密切相关（P〈0.05）。结论：Survivin、Ki-67在乳腺癌病例中均有较高表达,并且其特异性均很高,故临床检测Survivin、Ki-67对乳腺癌的病理诊断有较高的鉴别意义,具有临床推广价值。