DNA content and c-erbB-2 oncoprotein expression in hepatic metastases from colorectal carcinoma--in relation to clinicopathologic findings and prognosis

The nuclear DNA ploidy pattern and c-erbB-2 oncoprotein expression in primary and metastatic lesions were investigated using paraffin-embedded materials from 44 cases of colorectal carcinoma with hepatic metastases and 45 cases without hepatic metastases. The frequency of aneuploidy and positive staining of c-erbB-2 in primary tumor with hepatic metastases were significantly higher compared with those without hepatic metastases (p less than 0.05). There were significant correlations between diameter of metastases and DNA ploidy pattern of the metastases and between metachronous metastases, degree of metastases, vessel involvement and DNA ploidy pattern of the primary tumor. Positive staining of c-erbB-2 was detected more frequently with the advancement of depth of tumor invasion. There was no significant correlation between DNA ploidy pattern and c-erbB-2 expression. In the survival of patients whose primary tumor and hepatic metastases were resected, it was shown that DNA ploidy pattern of metastases was the most important independent prognostic factor. Expression of c-erbB-2 in primary tumor predicted the hepatic metastases.     

影响胰腺癌预后的因素分析

目的　探讨影响胰腺癌预后的决定因素。 方法　应用流式细胞仪检测胰腺癌ＤＮＡ倍体６２ 例,采用免疫组织化学法检测ｐ２１ 、ｐ５３ 在胰腺癌中的表达,应用Ｃｏｘ 比例风险模型对其预后因素进行分析。 结果　本组共有６２ 例经手术和病理学检查证实的胰腺癌病人,其中胰腺癌患者二倍体２５ 例,四倍体１１ 例,预后较好,平均生存期分别为２８ 个月和３０ 个月,非四倍体异倍体者２６ 例平均生存期仅为５ 个月。胰腺癌组织ｐ２１ 阳性率为８９％ ,ｐ５３ 阳性率为５１％ 。二者表达均与临床分期密切相关;单因素分析发现,ＤＮＡ倍体、后腹膜浸润、手术方式、肝转移、临床分期、ｐ２１ 表达、十二指肠浸润等与预后密切相关,多因素分析中仅ＤＮＡ倍体和临床分期是独立预后决定因素。 结论　ＤＮＡ倍体和临床分期是胰腺癌独立预后的决定因素     

Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas

To further investigate whether multiple genetic changes are involved in the development of colorectal cancer, we performed an immunohistochemical analysis of p53 and ras p21 protein expression in 139 specimens of colorectal adenoma with varying degrees of dysplasia, 57 specimens of early cancer with an adenomatous component, and 12 specimens of superficial early cancer without any adenomatous component. Positive p53 staining was found in 15% of the adenomas with moderate dysplasia and in 42% of the adenomas with severe dysplasia or intramucosal carcinoma (IMCA). Positive immunostaining of p53 was observed to be significantly correlated with the degree of dysplasia and the depth of invasion, as was the expression of ras p21. However, a closer correlation was observed with the increasing size of the adenomas. Furthermore, p53 staining was positive in 42% of the 12 superficial early cancer specimens, while ras staining was positive in only 1 specimen (8%). These results indicate that p53 gene overexpression may play some biological role in both the adenoma-to-carcinoma sequence and in de novo cancer development, whereas ras p21 expression may not be as involved in de novo cancer development as in the malignant conversion of colorectal adenomas.     

The immunohistochemical expression of BCL-2 oncoprotein in colorectal adenocarcinoma

The immunoreactivity forbcl-2 oncoprotein was determined in tumor tissue samples from 40 patients with colorectal adenocarcinoma. Positive immunoreactivity forbcl-2 oncoprotein was seen in 14 of the 40 tumor tissue samples (35%) and was found to be associated with a significantly higher incidence of synchronous liver metastasis (P=0.043); however, there was no correlation between the immunoreactivity forbcl-2 oncoprotein and tumor size, depth of tumor invasion, lymph node metastasis, or clinical stage of the disease. Among 33 patients who had undergone curative resection, disease-free survival did not differ significantly between 10 withbcl-2-positive tumors and 23 withbcl-2-negative tumors (P=0.498). The present study showed that the positive immunohistochemical expression ofbcl-2 oncoprotein was associated with a significantly higher incidence of liver metastasis from colorectal cancer, but it had no effect on the disease-free survival of patients who had undergone curative resection.     

Fluorescence in situ Hybridization and Immunohistochemical Analysis of p53 Expression in Endometrial Cancer: Prognostic Value and Relation to Ploidy

Background Endometrial carcinoma is the most common gynecological malignancy. Several molecular biological characteristics have been studied for their potential value in patient management. Objectives Our objectives were to compare p53 immunohistochemical expression with P53 gene status determined by fluorescence in situ hybridization (FISH) and to compare these characteristics with ploidy and with classical clinical and histological prognostic factors. Materials and Methods We reviewed stored specimens from 43 patients with endometrial cancer diagnosed in 1999–2004. P53 FISH and immunohistochemistry were performed, together with imaging cytometry to calculate DNA ploidy. Results Thirteen of the 43 endometrial carcinomas (30.2%) showed P53 loss of heterozygosity (LOH). P53 LOH correlated with the histological type (P = .03) and the histological grade (P = .004). Quantitative immunohistochemical expression of p53 protein correlated with the histological type (P = .0001). With a cutoff of 10% of p53-positive cells, p53 overexpression correlated with the histological type (P = .003) and grade (P = .0008). No relation was found between P53 LOH or immunohistochemical expression and the disease stage, the depth of myometrial invasion, lymph node status, lymphovascular space involvement, recurrence, or death from cancer. Nondiploid carcinomas showed deeper myometrial invasion than diploid carcinomas (P = .01). No relation was observed between ploidy and qualitative or semiquantitative p53 expression or P53 LOH. Conclusion In endometrial cancer, FISH analysis of P53 status adds no significant prognostic information compared with immunohistochemical p53 analysis.     

胆囊癌组织细菌L型的检测与p21及p53基因突变的关系

目的 探讨胆囊癌的发生与细菌L型感染和p21及p53基因突变的关系。方法 采用免疫组化SP法和革兰氏染色技术，对40例胆囊癌及40例慢性胆囊炎组织中的细菌L型和突变型p53蛋白及p21蛋白进行检测，并对胆囊癌组织中的细菌L型阳性伴p21及p53蛋白阳性表达结果和细菌L型阴性伴p21及p53蛋白阳性表达结果进行对比分析。结果 胆囊癌组织中革兰氏染色细菌L型检出率为77．5％(31／40)，明显高于胆囊炎的57．5％(23／40)，P＜0．05，且与免疫组化细菌L型抗原表达阳性率[80．0％(32／40)]具有一致性；胆囊癌组织中的p21及p53蛋白表达阳性率分别为62．5％(25／40)和65．0％(26／40)，明显高于胆囊炎组织中的p21及p53蛋白表达阳性率[2．5％(1／40)和5.0％(2／40)]，P＜0．05；胆囊癌组织中的细菌L型阳性者其p21及p53蛋白表达阳性率分别为75．0％(24／32)和78．1％(25／32)，明显高于细菌L型阴性者的p21及p53蛋白的表达阳性串率[12.5％(1／8)，12．5％(1／8)]，P＜0。05。结论 细菌L型参与了p21及p53基因的突变，并在胆囊癌的发生中可能起协同作用。     

人骨肉瘤中p53、p21~(WAF1/CIP1)和增殖细胞核抗原的表达及相互关系

目的 探讨细胞周期相关基因p21~(WAF1/CIP1)、p53和增殖细胞核抗原(PCNA)在人骨肉瘤中的表达和相互关系.方法 应用LSAB法,对40例骨肉瘤、20例骨软骨瘤患者的病变组织和20例正常人骨组织分别以p53、p21~(WAF1/CIP1)、PCNA蛋白的单克隆抗体作免疫组织化学检测.结果 骨肉瘤组织中p53、p21~(WAF1/CIP1)、PCNA蛋白的阳性反应率和阳性反应强度均明显高于骨软骨瘤和正常骨组织,其差异有统计学意义(P<0.05).p53标记指数与p21~(WAF1/CIP1)标记标数以及p21~(WAF1/CIP1)与PCNA标记指数间呈正相关(t值分别为2.93和4.20,P<0.01).结论 骨肉瘤组织中有p53、p21p21~(WAF1/CIP1)和PCNA的过表达,其表达的强度与肿瘤的恶性程度和预后相关.     

c-myc oncoprotein levels in bladder cancer

Summary The protein coded by the oncogene c-myc, p62^c-myc, was measured using monoclonal antibodies and flow cytometry in nuclei derived from paraffin-wax sections of transitional cell carcinomas of the human bladder. Superficial disease (stages pTa and pT1) which did not recur within 5 years of diagnosis had significantly higher oncoprotein levels than those which did recur or were muscle-invasive (stage pT2 or greater) at presentation (P<0.01). These preliminary findings indicate that oncoprotein levels might have prognostic significance for bladder cancer.     

PCNA and p53 in Urinary Bladder Cancer: Correlation with Histological Findings and Prognosis

Background This study aimed to immunohistochemically examine the expression of proliferating cell nuclear antigens (PCNA) and pS3 protein in transitional cell carcinomas (TCC) of the urinary bladder, and to investigate possible correlations of this expression with the tumor grade or stage, tumor recurrence, and prognosis of the disease. Materials and Methods The immunohistochemical status of the PCNA and p53 proteins were determined on paraffin-embedded sections from 128 patients with TCC of the urinary bladder, using PC-10 and D07 as the primary antibodies. Positive stainings were represented by scores (Labeling Index; LI, %) calculated as the percent of positive cells among all neoplastic cells counted. The findings were compared to the patients' histopathological features. Patients who underwent transurethral resection were divided into groups with low and high scores for PCNA and p53, respectively, and the tumor recurrence rate was compared among the groups. Patients who underwent total cystectomy were similarly divided into low and high score groups, and survival rates of the groups were compared. Results PCNA expression was observed in 66 of 128 patients (51.6%), with a mean labeling index of 26.6%. Overexpression of p53 was observed in 65 of 1 28 patients (50.8%), with a mean labeling index of 35.3%. There were significant correlations of the PCNA and p53 indices with both histological grade and stage of the tumor. In the TUR group, there were no statistically significant differences in recurrence rate between the groups with high or low scores for either PCNA or p53. In the total cystectomy group, there was a significant correlation between survival rate and positive staining for PCNA, but not for p53. The relationship between 2 parameters, PCNA and p53 scores, was not significant (linear correlation coefficient, r= 0.67). Conclusions PCNA and p53 status in transitional cell carcinomas of the urinary bladder is related to the histopathological findings. We also suggest that immunohistochemical staining for PCNA provides significant clinical information which may be useful in the initial selection of therapy. However, overexpression of p53 does not appear to represent an independent prognostic marker in bladder tumors.     

Detection of p53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications

Summary For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumorsuppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (T_a) tumors to 83.3% of muscle-invasive (T₃/T₄) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G₁ tumors to 75% of G₃ tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T₁) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10). After a median follow-up period of 54 months, 7 of 8 patients for whom more than 20% of cells stained positively for p53 had disease progression as compared with only 1 of 33 patients who were negative for p53 detection (P<0.01; chi-square test). For other urological tumors such as prostate cancer, the results of immunohistochemistry are more difficult to interpret and require definite confirmation on the DNA level.     

Expression of p53 protein related to human papillomavirus and DNA ploidy in superficial esophageal carcinoma

We examined the p53 protein and human papilloma virus (HPV) by immunohistochemistry and DNA ploidy by cytofluorometry in paraffin-embedded esophageal carcinoma tissue specimens. Sixty-one patients with superficial esophageal carcinoma were operated on between 1983 and 1991 without any prior treatment. Immunostaining of the anti-p53 protein antibody (CM1) was positive in 32 carcinomas (52%). Patients with p53-positive tumors had a poorer outcome than those with p53-negative tumors (P<0.05). In addition, patients with p53-positive tumors did not have any characteristic site of relapse. Only 5 of the 61 patients (8.2%) had HPV-positive tumors. One of these 5 carcinomas expressed both p53 protein and HPV. Three patients with HPV-positive tumors which had invaded the submucosal layer died of relapse. A determination of DNA ploidy revealed 30 patients with aneuploid tumors, 13 with polyploid tumors and 18 with diploid tumors. The outcome of the patients with aneuploid tumors was worse than that of the patients with diploid tumor (P<0.05). p53 protein expression was not associated with DNA ploidy; however, the 16 patients who had both p53-positive and aneuploid tumors had a worse prognosis than patients with p53-negative and aneuploid tumors (P<0.01). These findings suggest that p53 protein expression in conjunction with DNA ploidy may be a useful indicator in evaluating the prognosis of patients with superficial esophageal carcinoma.     

MDM2/p53 protein expression in the development of colorectal adenocarcinoma

The murine double minutes 2 (MDM2) oncoprotein inhibits p53-mediated tumor suppression. MDM2 has been shown to be overexpressed in sarcomas and more recently was implicated in the pathogenesis of carcinomas. The purpose of this study was to determine the expression pattern of MDM2 in adenomas and colorectal adenocarcinomas and decide whether there is a correlation between MDM2 and p53 protein status. Paraffin-embedded tissues from 52 colorectal cancer (CRC) specimens and their adjacent normal tissue (N-CRC) were studied. In addition, 56 sporadic adenomas were investigated for the immunohistochemical expression of MDM2 and p53 proteins. Immunoreactivity of p53 indicating p53 gene mutation (p53 +) was significantly higher in CRC (44%) compared to adenomas (23.2%) (P <0.01). None of the N-CRC specimens expressed the immunoreactive p53 protein. MDM2 overexpression (MDM2+) was similar in adenomas (30.3%) and CRC (25%), but only 2 (3.8%) of 52 N-CRC specimens showed overexpression of MDM2. In most cases MDM2 expression was associated with negative p53 expression (wild-type p53) in both adenomas (r = 0.59, P <0.001) and CRC (r = 0.69, P <0.0001). No correlation was found between MDM2, p53 expression, and either the histologic grade, nodal stage or morphology of the tumors. There is greater p53 mutation in CRC compared to adenomas and N-CRC. The data indicate that MDM2 is overexpressed in CRC and is significantly associated with wild-type p53 compared to N-CRC specimens from the same patient. The MDM2 expression pattern is similar in adenomas and CRC, which may suggest that MDM2 overexpression is an early event in the progression of CRC. Supported by a grant from The Methodist Hospital Foundation, Houston, Tex. Presented at the Fortieth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Fla., May 16–19, 1999.     

p27蛋白在原发性胆囊癌中的表达及其意义

目的探讨p27蛋白在原发性胆囊癌中的表达及其意义.方法应用免疫组织化学SABC法检测原发性胆囊癌中p27蛋白的表达.结果p27蛋白在原发性胆囊癌中的阳性表达率为25%(11A4),低于良性病变(P<0.05),p27蛋白表达在肿瘤不同病理分级中未见明显差异(P>0.05),但与Nevin分期呈显著负相关(P<0.05),有癌转移者明显低于未转移者(P<0.05).结论p27蛋白可作为原发性胆囊癌的生物学标记物.     

Prognostic significance of tumor angiogenesis,Ki 67, p53 oncoprotein,epidermal growth factor receptor and HER2 receptor protein expression in undifferentiated nasopharyngeal carcinoma--a prospective study

BACKGROUND: This study prospectively examines the prognostic role of p53 oncoprotein (p53), Ki67-antigen (Ki67), tumor angiogenesis (MVD), epidermal growth factor receptor (EGFR), and HER2 receptor protein (HER2) expression in Chinese with undifferentiated nasopharyngeal carcinoma (NPC). METHODS: Seventy-eight Chinese were recruited from October 1995 to July 1997 at the Prince of Wales Hospital, Hong Kong. Pretreatment immunohistochemical preparations of the primary tumor were made, and clinical data were collected prospectively until October 30, 2000. The markers were correlated with overall survival (OS), disease-free survival (DFS), time to progression (TTP), and UICC stage. RESULTS: On univariate analysis, EGFR expression correlated with poorer OS (p =.0001), DFS (p =.01), shorter TTP (p =.0001), and advanced T stage (p =.036). Strong EGFR expression, when compared with weak or moderate, was associated with poorer OS (p =.04) and shorter TTP in a subgroup of patients with UICC stage III-IV disease. HER2 expression was associated with advanced UICC stage (p =.006). The presence of p53 expression correlated with poorer DFS (p =.01) and a trend toward shorter TTP (p =.06). No correlation was found with Ki67-antigen or MVD. On multivariate analysis, only EGFR expression was significantly linked to shorter OS and TTP. CONCLUSIONS: EGFR expression in undifferentiated NPC is associated with a poor clinical outcome. A prognostic role of p53 and HER2 expression is suggestive but not consistently defined in this study. The relatively high prevalence of positive staining for EGFR supports the use of molecular targeted therapy in this disease.     

Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma

BACKGROUND: A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of cyclooxygenase-2 (COX-2) and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53. METHODS: Immunohistochemistry was used to determine the expression of COX-2 and p27. The correlation with survival of these factors and of p21 and p53 expression was assessed by univariate and multivariate analyses. RESULTS: A positive statistically significant correlation was found between p27 and p21 expression (p<0.0001), but there was a negative correlation between COX-2 expression and both p27 (p = 0.001) and p21 (p<0.0001). No statistically significant correlation was recorded between p53 and all the other immunohistochemical parameters. Univariate analysis showed that overall survival was strongly influenced by p21, p27, and COX-2 expression, but multivariate Cox regression analysis showed that the only immunohistochemical parameter to influence overall survival of patients with mesothelioma was COX-2. CONCLUSIONS: These findings suggest that COX-2 expression may be a useful prognostic parameter for mesothelioma.     

p16、p21蛋白和增殖细胞核抗原在胃癌中的表达及其相互关系

目的 探讨p16、p21蛋白和增殖细胞核抗原（PCNA）在胃癌发生、发展中的作用及临床意义。方法 应用免疫组织化学法,以46例胃癌及癌旁组织中p16 、p21蛋白和PCNA进行检查。结果 胃癌组织中p16、p21蛋白和PCNA的阳性率分别为21．05％、28．26％、73．91％,与癌旁组织中的阳性率为58．705、65．21％、23．91％差异有显著性（P＜0．05）。在胃癌的不同病理参数（淋巴结转移,分化程度,浸润深度及TNM分期）中,p16,PCNA和p21蛋白表达则分别在全部4个,前2个,前2个参数中存在着明显差异（P＜0．05）。p16、p21蛋白和PCNA在肿瘤的部位、大小、患者性别及年龄间差异无显著性（P＞0．05）。p16原癌基因蛋白质与PCNA,p21与PCNA阳性表达存在明显差异（P＜0．05）,而p21表达与p16表达之间则差异无显著性（P＜0．05）。结论 p16、p21蛋白和PCNA是胃癌发生、发展过程中的重要因素,且与胃癌临床病理参数密切相关。     

抑癌基因PTEN和p16在肝细胞性肝癌中的表达及其意义

目的探讨PTKN和p16基因在肝细胞性肝癌（HCC）中的表达及其意义。方法采用免疫组化技术S—P法检测PTKN蛋白及p16蛋白在43例HCC及其相应癌旁组织中的表达。结果PTKN蛋白在HCC组织中的阴性表达率明显高于在癌旁组织中的阴性表达率（P〈0．01）;PTKN蛋白表达阴性率与HCC的分化程度、临床分期呈负相关,与AFP甲值及有无转移、HBV感染相关,与p16蛋白缺失率呈正相关,而与患者年龄、性别、肿瘤直径无关。比较PTKN阴性表达和阳性表达的HCC患者的术后1,3,5年生存率,差异在统计学上有显著性意义。结论PIEN失活部分参与了HCC的发生、发展进程。PIEN基因、p16基因的失活及HBV感染可能在HCC的发生、发展中存在协同关系。PTEN蛋白表达的检测可为HCC患者术后的预后判断提供参考。     

IMMUNOHISTOCHEMICAL DETECTION OF p53 PROTEIN OVEREXPRESSION VERSUS GENE SEQUENCING IN URINARY BLADDER CARCINOMAS

PURPOSE: Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. MATERIALS AND METHODS: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. RESULTS: The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001). The correlation between the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p<0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p<0.0001). However, in multivariate analysis, only stage was significantly correlated to prognosis (p<0.0001). CONCLUSIONS: The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.     

c-myc、MDM2及p53基因在原发性腹膜后脂肪肉瘤中的表达及临床意义

目的:探讨原发性腹膜后脂肪肉瘤中c-myc、MDM2及p53基因蛋白表达及三者与肿瘤发生、发展的关系。方法:应用免疫组化PV-6000两步法对原发性腹膜后脂肪肉瘤及脂肪瘤组织中c-myc、MDM2及p53基因蛋白的表达进行检测,并进行统计学分析。结果:c-myc、MDM2及p53蛋白在原发性腹膜后脂肪肉瘤中表达阳性率分别为58.3%(28/48)、64.6%(31/48)、50.0%(24/48),三种蛋白在脂肪肉瘤与脂肪瘤组织中的阳性率差异有显著性(P0.05)。三种蛋白均与患者的年龄、性别及肿瘤大小无相关性。不同类型脂肪肉瘤分化较好者阳性率明显低于分化较差者。原发性腹膜后脂肪肉瘤中c-myc、MDM2及p53蛋白表达呈正相关(P0.05),c-myc、MDM2及p53蛋白表达在原发者与复发者之间的差异均无统计学意义(P0.05)。结论:c-myc、MDM2及p53蛋白与原发性腹膜后脂肪肉瘤的形成、分化及恶性程度有关,它们可作为判断原发性腹膜后脂肪肉瘤分化程度及恶性程度参考指标之一,但与肿瘤复发无关。在脂肪肉瘤的发生、发展中三者可能起协同作用。     

乳腺癌组织中Skp2和p27Kip1表达与临床病理因素的关系

目的:探讨乳腺癌组织中Skp2与p27Kip1的表达及其意义。方法:采用免疫组化法两步检测法检测正常乳腺组织、导管上皮不典型增生组织(ADH)以及浸润性导管癌(IDC)组织中的Skp2与p27Kip1的表达,并分析两者表达与乳腺癌淋巴结转移及组织学分级的关系。结果:Skp2阳性表达率在正常乳腺组织、ADH组织、IDC组织依次升高,伴腋窝淋巴结转移的IDC组织中Skp2阳性表达率明显高于无淋巴结转移的IDC组织,而p27Kip1的表达则与Skp2的表达呈反向变化(均P0.05);不同组织学分级IDC组织间Skp2阳性率、p27Kip1阳性率差异均有统计学意义(均P0.05),且Skp2阳性表达与IDC组织学分级呈正相关(r=0.492,P0.05),而p27Kip1的阳性表达与IDC组织学分级呈负相关(r=-0.327,P0.05)。结论:乳腺癌组织中Skp2表达上调而p27Kip1表达下调,两者的变化程度与乳腺癌的恶性生物学特征密切相关。