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.     

抗凋亡基因bcl—2在膀胱肿瘤中的表达及意义

应用链菌素亲和素－过氧化物酶（ＬＳＡＢ）免疫组织化学技术对４９例膀胱肿瘤石蜡切片ｂｃｌ－２原癌基因蛋白的表达进行研究，结果显示，在各级（期）膀胱肿瘤中均为ｂｃｌ－２基因表达，随着肿瘤分级，分别的增加，ｂｃｌ－２基因表达增多，但无显著性差异（Ｐ〉０．０５），在〉５０岁以上患者中ｂｃｌ－２基因表达率明显高于≤５０岁者（Ｐ〈０．０５）。虽然在复发肿瘤和多发肿瘤及男性患者ｂｃｌ－２基因表达有增加趋势，但其     

Expression of BCL-2 oncoprotein on tumor cells and tumor-infiltrating lymphocytes (TIL) in meningiomas

The Expression of the antiapoptotic oncoprotein BCL-2 and its correlation to tumor grade in 62 meningiomas (48 classic, 9 atypical, and 5 anaplastic) using single and double immunohistochemistry was investigated. BCL-2 expression was found in two different cell populations identified as lymphocytes (BCL-2+CD3+) and tumor cells (BCL+/CD3–). Tumor-infiltrating lymphocytes (TIL) (CD3+) were found within classic (9.5% of cells), atypical (2.4% of cells), and anaplastic (1.8% of cells) meningiomas. In classic meningiomas, 66.5% of TIL were BCL-2-positive, in atypical meningiomas 79.2%, and in anaplastic meningiomas 37.9%. In 33 (68.8%) of the classic meningiomas, medium to high counts of BCL-2+ tumor cells were detected. Atypical meningiomas showed nearly equal percentages of high (two patients), medium (five patients), and low (two patients) BCL-2+ tumor cell counts, whereas anaplastic meningiomas showed only medium (two patients) and low (three patients) BCL-2 tumor cell counts or were BCL-2-negative (one patient). In summary, a significant inverse correlation between the number of BCL-2-positive tumor cells and tumor grade in meningiomas was found. These findings support the hypothesis of cell survival prolongation by the antiapoptotic ability of BCL-2 proto- oncogenes and demonstrate the prognostic relevance of BCL-2 immunoreactivity in meningiomas. Received: 10 June 1998 / Accepted: 23 February 1999     

Comparison of p53 and bcl-2 expression in initial, synchronous, and metachronous colorectal adenomas

To investigate the significance of p53 and bcl-2 expression in metachronous colorectal adenomas arising in the remaining colon after carcinoma resection, we analyzed p53 and bcl-2 expression immunohistochemically in initial adenomas (type I), synchronous adenomas with concurrent carcinoma (type II), and metachronous adenomas arising after resection of initial adenomas (type III) or carcinoma (type IV). The incidence of p53 immunoreactivity in type IV adenomas with mild dysplasia was significantly higher than that in type I, type II, or type III adenomas with mild dysplasia. bcl-2 immunoreactivity was more frequently detected in type IV adenomas with mild dysplasia than in type I or type III adenomas with mild dysplasia. Coexpression of p53 and bcl-2 was detected in 16% of the type IV adenomas, this being a significantly higher frequency than that seen in the type I, type II, or type III adenomas. These results suggest that the evaluation of p53 and bcl-2 in metachronous adenomas in the remaining colon after resection of carcinoma may be a useful biologic marker for assessing the risk of cancer development. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan     

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.     

hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Background The aim of this study was to search for mutations in the humanmutS homolog 2 (hMSH2) and humanmutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC). Methods The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing. Results Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. ThehMLH1 gene had a higher mutation detection rate thanhMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in thehMLH1 gene and four in thehMSH2 gene. Conclusions ThehMLH1 gene had a higher mutation detection rate thanhMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.     

Higher expression of oncoproteins c-myc,c-erbB-2/neu,PCNA, and p53 in metastasizing colorectal cancer than in nonmetastasizing tumors

Background: Expression of individual oncogenes may predict outcome in patients with metastatic colorectal cancer (CRC). We studied the oncogene profile in the tumors of patients with CRC and assessed their value as predictors of liver metastases. Methods: The oncoproteins c-myc, c-erbB-2/neu (c-neu), PCNA and p53, were measured by immunohistochemistry in sections of metastasizing human CRC (n=34) and their liver secondaries as well as in sections of nonmetastasizing CRC (n=25). Results: The metastasizing primary CRC expressed proliferating-cell nuclear antigen (PCNA), c-neu, and c-myc at significantly higher levels than the nonmetastasizing primary cancer. p53 was also overexpressed in the metastatic group compared with the nonmetastasizing CRC, but this difference was not significant. The frequency of expression of all these markers was similar in the metastasizing primary CRC and the liver secondaries from the same patients. There was no correlation between the expression of the individual markers and histological grade, DNA ploidy, and subsequent local recurrence and lung metastasis and survival. However, when both groups were assessed together, positive expression of c-myc was more likely to occur in poorly differentiated tumors, whereas PCNA expression increased with more advanced Dukes stages. Conclusion: These results suggest that the overexpression of c-myc, c-neu, PCNA, and p53 may occur in CRC that are likely to metastasise to the liver.     

Paratesticular metastasis from colorectal adenocarcinoma

Paratesticular tumors are rare, especially when they are metastatic. Most of them originate in the prostate, kidney, gastrointestinal tract, lung, and breast. The most common site of metastasis from the gastrointestinal tract is the colon. A 75-year-old male presented with a painless and tense right scrotal mass. He underwent a radical right orchiectomy, and the pathology revealed mucinous cystadenocarcinoma of the paratesticular tissue. Computed tomography revealed focal wall thickening at the rectosigmoid junction and liver nodules. The colonoscopic biopsy of the mass showed adenocarcinoma. Immunohistochemical staining of both sites confirmed the diagnosis of colorectal adenocarcinoma metastatic to the scrotum.     

DNA ploidy,c-myc oncoprotein p62 and v-H-ras oncoprotein p21 in colorectal carcinoma

DNA ploidy and expression of the c-myc oncoprotein p62 and the v-H-ras oncoprotein p21 were examined in 54 colorectal carcinomas. DNA ploidy, determined by DNA flow cytometry, was diploid in 19 samples and aneuploid in 35. Expression of the p62 oncoprotein, determined by immunohistochemical staining, was intensely positive in 18 samples while that of the p21 oncoprotein, also determined by immunohistochemical staining, was positive in 29. There was no correlation between DNA ploidy and expression of the p62 oncoprotein, and DNA ploidy did not correlate with expression of the p21 oncoprotein. There was, however, a close correlation between expression of the p62 oncoprotein and that of the p21 oncoprotein being P<0.01 according to Peason's chisquare test.     

原发性肝癌组织中C-myc癌基因、Ki-67抗原的表达与意义

目的探讨原发性肝癌组织中Ｃ－ｍｙｃ癌基因，Ｋｉ－６７抗原的表达与其临床病理关系。方法应用免疫组织化学方法（ＡＢＣ法）检测１０例正常人肝组织，３７例原发性肝癌组织Ｃ－ｍｙｃ，Ｋｉ－６７表达水平。结果Ｇ－ｍｙｃ，Ｋｉ－６７阳性表达率在低分化肝癌（８６．４％，５７．７％）均高于在高分化肝癌（４５．５％，９．１％）Ｐ＜０．０５；其在肝癌伴淋巴结转移（８６．９％，６１．０％）高于在不伴淋巴结转移者（５０．０％，１４．０％）Ｐ＜０．０５。结论Ｃ－ｍｙｃ癌基因过度表达与肝癌的增殖、浸润有关，Ｋｉ－６７的表达水平有助于判断肝癌的病理分型。     

结肠癌中hTERT的表达及其与Survivin和bcl-2表达的关系

目的：研究端粒酶逆转录酶（hTERT）在结肠癌中的表达及其与Survivin和bcl-2表达的关系。方法：应用免疫组织化学SABC法检测52例结肠癌及其相应癌旁正常组织中hTERT、Survivin和bcl-2的表达。结果：52例结肠癌组织中hTERT表达阳性率为80.8%,而相应癌旁正常结肠组织中无一例阳性表达。hTERT表达的上调与患者性别、年龄、肿瘤浸润深度无明显相关（P〉0.05）,而与肿瘤分化程度、淋巴结转移、Dukes分期明显相关（P〈0.05）。在52例结肠癌组织中hTERT与Survivin以及hTERT与bcl-2的表达之间呈正相关（r=0.589,P〈0.05;r=0.559,P〈0.05）。结论：hTERT表达的上调与结肠癌的发生、发展、恶性程度有着密切的关系;结肠癌中hTERT的表达与Survivin和bcl-2的表达密切相关。     

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.     

Angiogenesis and p53 at the invading tumor edge: prognostic markers for colorectal cancer beyond stage

BACKGROUND: Angiogenesis has emerged as a major prognostic factor in many human malignancies and it is a prospective target for cancer therapy. MATERIALS AND METHODS: In this study, we investigated immunohistochemically the angiogenic activity and the expression of p53 and bcl-2 proteins in a series of 170 operable colorectal carcinomas, stage B and C. RESULTS: A high vascular density at the invading tumor front was directly related to nuclear p53 accumulation, and inversely to cytoplasmic expression of bcl-2. Furthermore, high angiogenic activity was significantly associated with lymph node metastasis. Survival analysis showed that Dukes stage and vascular density were the most important and independent prognostic factors in colorectal cancer. DISCUSSION: It is believed that angiogenesis at the invading tumor edge can be used as an independent prognostic marker to identify subgroups of colorectal cancer patients with an unfavorable post-operative outcome.     

Levels of serum-soluble receptor for interleukin-2 in patients with colorectal cancer

P < 0.05). Markedly elevated levels of serum-soluble IL-2R were recognized in patients with stage IV cancer, those with Dukes' stage D cancer, and those with liver metastasis. Moreover, the prognosis of patients with low levels of IL-2R (<531 U/ml) was significantly better than that of those with high levels (P < 0.05). These findings demonstrate that an elevated concentration of soluble IL-2R might be a useful indicator of liver metastasis and poor prognosis in patients with colorectal carcinoma. (Received for publication on June 17, 1997; accepted on Jan. 6, 1998)     

ITGAV在结直肠癌中的表达及临床意义

目的 探讨整合素αv(ITGAV)在结直肠癌中的表达和临床意义.方法 采用免疫组织化学法检测91例结直肠癌组织及18例癌旁组织中ITGAV的表达,分析ITGAV的表达与临床病理因素的关系.利用GEO和TCGA数据库下载结直肠癌ITGAV的表达及临床随访数据进行生存分析.结果 ITGAV在结直肠癌组织中的表达显著高于癌旁...     

散发性结直肠癌微卫星不稳定性与Mt-p53及bcl-2蛋白表达的研究

目的 探讨散发性结直肠癌微卫星不稳定性民Mt-p53及bcl-2蛋白表达的关系。方法 应用聚合酶链式反应（PCR）技术检测了48例散发性结白肠癌中四个位点的微卫星不稳定性,同时应用免疫组织化学技术对癌基因bcl-2、抑癌基因Mt-p53蛋白的表达。结果 ①48例散发性结直肠癌中四个微卫星位点D2S123、BAT-26、D17S261、D16S799的微卫垦不稳定性检出率分别为12.5％、18.8％、10.4％、8.3％;②Mt-p53蛋白和bcl-2蛋白阳性个分别为66.7％和77.1％;③微卫星不稳定性与mt-p53和bcl-2蛋白的表达均相差个显著（P>0.05）。结论 微卫星不稳定性引起散发性结直肠癌的RER途径是不同于由抑癌基因p53失活及癌基因bcl-2的激活引起的LOH途径的新致癌机制。     

血清脂联素在结直肠癌中表达的研究

目的 探讨结直肠癌血清中脂联素的表达,并对影响脂联素水平的因素进行分析。 方法 选择2010年1月至2010年6月中国医科大学附属盛京医院收治的90例结直肠癌病人作为研究组,选择30名健康成年人作为对照组。用双抗体夹心ABC-ELISA法测定血清的脂联素水平,对结直肠癌不同临床病理特征下的血清脂联素水平差异进行统计分析。 结果 研究组血清脂联素水平（13.08±7.99）μg/mL明显低于对照组（21.92±8.76）μg/mL（P＜0.01）,以男性更为明显。研究组随着肿瘤TNM分期的增加,血清脂联素水平呈现进一步下降的趋势（P<0.05）,肿瘤的不同部位、不同组织学分级间的血清脂联素水平没有明显差异（P >0.05）。 结论 结直肠癌病人血清的脂联素水平要明显低于正常健康人,且随着肿瘤分期的增加,血清脂联素水平呈现进一步下降的趋势。