Microvascular architecture of experimental colon tumors in the rat

Tumor cell proliferation is dependent upon concurrent growth of a supporting vasculature. This study aims to characterize the structural features of the microvasculature within a primary tumor model. There were 22 colon tumors induced in 16 rats by repeated administration of dimethylhydrazine. A cast of the microvessels was prepared by intraarterial administration of acrylic resin (Mercox). After corrosion of the tissue, the cast was examined by scanning electron microscopy. Tumors 2.6 to 12.0 mm in diameter were examined. Within polypoid carcinomas up to 5.7 mm in diameter, there were two distinct vascular zones, a luminal vascular zone continuous with the vasculature of normal mucosa and a central zone continuous with the normal submucosa and muscularis propria vessels. Within both vascular zones, the organization of microvessels had the same general pattern as in normal mucosa. However, in tumors with diameters greater than 5.7 mm, the vasculature was seen to be disorganized and of a greater density than normal. In the smallest tumors, few morphological changes were seen in the individual microvessels when compared to normal. However, with tumor growth, there was elongation and increased diameters of the microvessels within the tumor. Microvessels within the luminal zone of the tumors which could definitely be traced to veins had diameters of 50 to 100 microns (compared to 12 to 30 microns for normal venules). Individual microvessels varied in diameter along their course forming saccular dilations in places. Networks of frequently anastomosing microvessels were formed. Extravasation of resin occurred from some microvessels. Elongated vessels of uniform diameter which travel distances up to 2 mm without branching were seen and were probably arterioles. These appearances indicate that there are two distinct stages of development of the vasculature within primary tumors, an early phase where the tumor is supplied by the preexisting host microvessels, followed by a phase of proliferation of new vessels with abnormal morphological characteristics.     

Codon 201 polymorphism of DCC gene is a prognostic factor in patients with colorectal cancer

The polymorphism at codon 201 of the "deleted in colorectal carcinoma" (DCC) gene has been liked to susceptibility to colorectal cancer. However, its clinicopathological significance has not been reported. We examined the codon 201 polymorphism and loss of heterozygosity (LOH) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 59 colorectal cancers, 48 samples from transitional mucosa and 67 samples from normal mucosa. The frequencies of the polymorphism did not significantly differ from normal to transitional mucosa and to tumor, but LOH was increased from transitional mucosa to tumor. Almost all of the LOH cases showed the polymorphism. The polymorphism was increased from well/moderately to poorly differentiated and to mucinous carcinoma (P=0.03). The polymorphism was more frequently seen in advanced stages than in earlier stages (P=0.02), and further predicted worse survival (P=0.04). The data suggest that the codon 201 polymorphism of the DCC gene was a target of LOH, and predicted prognosis in colorectal cancer patients.     

KAI1基因表达与大肠癌发生、发展的关系

 目的 探讨KAI1基因的表达与大肠癌(CRC)发生、发展的关系. 方法 采用RT-PCR法及免疫组织化学(EnvisionTM法)检测40例大肠癌组织、8例癌旁黏膜和8例正常黏膜的KAI1 mRNA和蛋白表达. 结果 正常黏膜KAI1 mRNA水平显著低于癌组织(P<0.05),癌旁黏膜略高于正常黏膜,但无显著差异;在大肠癌原发灶中,KAI1蛋白表达阳性25例(62.5%),弱阳性9例(22.5%),阴性6例(15%).KAI1 mRNA及蛋白水平在低分化、伴淋巴结转移肿瘤中表达显著降低(P<0.01,P<0.01;P<0.05,P<0.05). 结论 KAI1的异常表达可能参与了大肠癌的发生、发展,并对肿瘤的分化、淋巴结转移的判断有一定指导意义。     

结直肠肿瘤微血管计数及血管内皮细胞生长因子表达

目的 探讨血管生成与结直肠肿瘤的发生,发展关系,评估微血管计数（ＭＶＤ值）及血管内皮细胞生长因子（ＶＥＧＦ）表达与结直肠肿瘤预后的相关性。方法 应用免疫组化法回顾性地研究了３２例结直肠肿瘤石蜡包埋的病理组织。结果 正常粘膜,腺瘤,癌组织的ＭＶＤ值递增。不同病理状态下的结直肠癌ＭＶＤ值有差异,ＶＥＧＦ阴性组ＭＶＤ值低于ＶＥＧＦ阳性组,低ＭＶＤ值主ＶＥＧＦ阴性组生存率高于高ＭＶＤ值组及ＶＥＧＦ阳性组。     

Expression of TAG-72 in normal colon, transitional mucosa, and colon cancer

Monoclonal antibody (MAb) B72.3 detects an epitope carried by high-molecular-weight mucins (tumor-associated glycoprotein, TAG-72) recently identified as sialyl-Tn. B72.3 MAb has a restricted pattern of reactivity with normal tissues but it reacts with a high proportion of epithelial cancers. To determine the possible relationship between neoplastic transformation and reactivity with B72.3 MAb, we have analyzed samples of normal colon, colon cancer and transitional mucosa (mucosa adjacent to colorectal cancer) or reactive mucosa (mucosa adjacent to squamous carcinoma of the anal canal, or mucosa overlying lymphoma). B72.3 MAb reacted strongly with 21/21 specimens of transitional mucosa and with 17/21 specimens of adjacent colon cancer. Reactivity of B72.3 MAb with transitional mucosa was strong and homogeneous, whereas reactivity with cancer tissue was weaker and more heterogeneous. Reactive mucosa adjacent to squamous carcinoma or lymphoma was also reactive with B72.3 MAb. Our findings show that, in the colon, expression of TAG-72 antigen occurs during the process of epithelial cell transformation but is also regulated by factors unrelated to the process of carcinogenesis.     

The mucin profile in the mucosa of the large intestine in neoplasms]

Qualitative and quantitative changes in secretion of goblet cells of large bowel mucosa in adenomatous polyps (60), adenocarcinoma (30) and bioptates of adjacent transitional mucosa (30) were studied. As neoplasia progressed, mucin profile appeared to follow a certain pattern: it reached its peak in moderate dysplasia in polyps containing predominantly sulphomucins; subsequently both sulphomucin and sialomucin levels decreased. Adenocarcinomas showed a sharp drop in glycoprotein level, and an insignificant build-up of sialomucins was registered in some cases only. Enhanced abnormal secretion was observed in mucinous carcinoma and adenocarcinoma characterized by the presence of large mucinous areas. Also, qualitative changes were identified in transitional mucosa adjacent to tumor.     

直肠癌旁粘膜中细胞动力学的研究

目的探讨直肠癌旁粘膜的细胞生物学特性和范围大小。方法应用放射自显影双标记法检测１０例直肠癌旁粘膜的细胞动力学参数。结果距腺癌８ｃｍ范围内的肠粘膜，与正常粘膜相比，均有明显的腺体标记细胞上移、标记指数（ＬＩ）升高、细胞ＤＮＡ合成时长（Ｔｓ）延长、细胞周期时长（Ｔｃ）缩短。且上述变化呈现移行趋势，即距离腺癌越近，其异常变化的程度亦相对越重。结论直肠癌旁粘膜很可能属于癌前病变，其范围应不小于８ｃｍ。     

72例膀胱移行细胞癌中Fas和FaslL的表达

目的：探讨细胞凋亡基因Ｆａｓ和ＦａｓＬ在膀胱癌保作用及与肿瘤生物学行为和预后之间关系。方法：应用免疫组化方法检测１６例正常膀胱粘膜和７２例膀胱移行细胞癌标本中Ｆａｓ和ＦａｓＬ表达。结果：膀胱癌中Ｆａｓ和ＦａｓＬ表达均显著低于正常膀胱粘 中表达；Ｆａｓ表达与肿瘤分级、分期和复发之间均密切相关，但ＦａｓＬ表达与三者之间均无相关性。结论：Ｆａｓ和ＦａｓＬ系统异常可能是膀胱癌发生发展过程中免疫逃避的重要因     

P33ING1、p53基因在膀胱移行细胞癌中的表达及其意义

目的探讨抑癌基因P33ING1在膀胱移行细胞癌中的表达及其与p53蛋白表达的相关性。方法采用免疫组化S-P法,检测83例膀胱移行细胞癌及11例正常膀胱黏膜组织中P33ING1、p53的表达。结果83例膀胱移行细胞癌组织中P33ING1蛋白阳性表达率为59．03％,而正常膀胱黏膜组织中P33ING1蛋白阳性表达率为90．90％。P33ING1蛋白表达与膀胱移行细胞癌的WHO肿瘤分级相关。根据Spearman相关分析表明P33INGI蛋白表达与p53蛋白表达呈正相关关系（P〈0．05）。结论P33ING1基因可能在膀胱移行细胞癌的发生、发展过程中起重要作用,P33ING1与p53基因具有协同作用,同时检测p53和P33ING1表达水平,对膀胱癌的诊断、治疗和预后判断可能具有积极意义。     

COX-2、Ki-67和VEGF在膀胱移行细胞癌中的表达及意义

 目的 探讨环氧化酶-2（COX-2）在膀胱移行细胞癌中的表达及临床意义。方法 应用免疫组织化学法检测50份膀胱移行细胞癌患者手术后存档标本和10份正常膀胱黏膜组织中COX-2、血管内皮生长因子（VEGF）和增生细胞核抗原（Ki-67）的表达。结果 COX-2在膀胱移行细胞癌组织中阳性表达率为80 %，而在正常膀胱黏膜组织中无表达，差异有统计学意义。而且不同分期、不同分级间表达差异亦有统计学意义，即与分级、分期呈正相关；初发组COX-2表达高于复发组；单发组与多发组差异无统计学意义。在膀胱移行细胞癌组织中COX-2的表达与Ki-67的表达呈正相关；COX-2与VEGF在膀胱移行细胞癌组织中的表达呈正相关。结论 COX-2在肿瘤发生、发展中可能起着促进细胞增生的作用。VEGF的表达与COX-2呈正相关，表明VEGF可能是COX-2促进肿瘤血管生成的重要介质     

Expression of a novel family of epitopes on small intestinal mucins in colorectal cancers, adjacent and remote mucosa.

We describe the production, immunochemical and immunohistochemical characterization of monoclonal antibodies (MAbs) raised against the oncofetal small intestinal mucin antigen (SIMA). Four MAbs, reacting with distinct neuraminidase-sensitive SIMA epitopes, were shown to define a novel differentiation-associated relationship of SIMA epitopes within the normal small intestinal villus. Using Swiss rolls of 15 entire colorectal cancer resections, inappropriate expression of SIMA epitopes was detected in all cancers, in adjacent transitional mucosa and remote morphologically normal mucosa, extending as far as resection margins (73%). SIMA expression, whether preexisting or reactive to the tumor, may predispose to malignant change and tumor recurrence.     

hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells

Colorectal cancers exhibit a high telomerase activity, usually correlated with the hypermethylation of the promoter of its hTERT catalytic subunit. Although telomerase is not expressed in normal tissue, certain proliferative somatic cells such as intestinal crypt cells have demonstrated telomerase activity. The aim of this study was to determine whether a correlation exists between telomerase activity, levels of hTERT methylation and telomere length in tumoral and normal colorectal tissues. Tumor, transitional and normal tissues were obtained from 11 patients with a colorectal cancer. After bisulfite modification of genomic DNA, hTERT promoter methylation was analyzed by methylation-sensitive single-strand conformation analysis (MS-SSCA). Telomerase activity and telomere length were measured by a fluorescent-telomeric repeat amplification protocol assay and by Southern blotting, respectively. A significant increase of hTERT methylation and telomerase activity, and a reduction of the mean telomere length were observed in the tumor tissues compared to the transitional and normal mucosa. In the transitional and normal mucosa, telomerase activity was significantly lower than that in tumor tissues, even with high levels of hTERT methylation. Nevertheless, hTERT promoter methylation was not linearly correlated to telomerase activity. These data indicate that hTERT promoter methylation is a necessary event for hTERT expression, as is telomerase activity. However, methylation is not sufficient for hTERT activation, particularly in normal colorectal cells.     

Investigation of pericytes, hypoxia, and vascularity in bladder tumors: association with clinical outcomes

The contribution of endothelial cell growth to angiogenesis has been widely studied; however, the involvement of pericytes is less well documented, especially in human tumors. In this study we aimed to quantify and assess the prognostic significance of pericyte coverage, the extent of hypoxia, and microvessel density (MVD) in normal bladder mucosa and urothelial carcinoma. Antibody to alpha-smooth muscle actin was used to assess the distribution of pericytes (mural/smooth muscle cells) in the microvessels of normal human bladder (n = 4) mucosa and in urothelial carcinoma (n = 47) samples; this was quantitated using microvessel pericyte index (MPI). The MVD was measured using two different methods (n = 47) and hypoxia was assessed using glucose transporter-1 (Glut-1) staining (n = 30). There was a 70% reduction in MPI in urothelial carcinomas compared to normal bladder mucosa (p < 0.0012); MPI did not correlate with tumor stage or grade. Ta and T1 superficial tumors were divided into two groups with a MPI of <15% or >15%. Progression-free survival was significantly shorter for tumors with MPI >15% (p = 0.0036). MVD had no prognostic value using either evaluation method. Glut-1 immunoreactivity was not prognostic in superficial urothelial carcinoma samples. Tumors with a higher MPI showed a greater Glut-1 immunoreactivity (p = 0.0051). Microvessels in urothelial carcinoma have a considerable loss of pericyte coverage compared to normal bladder mucosa. The data from this preliminary study indicate that progression-free survival was shorter in patients whose superficial tumors had higher pericyte coverage of the microvessels. This may be due to increased levels of hypoxia, as demonstrated by a significant increase in Glut-1 staining.     

PD-ECGF mRNA表达与膀胱移行细胞癌侵袭性的关系

目的　研究血小板衍化内皮细胞生长因子 (PD ECGF)的mRNA表达在膀胱移行细胞癌生长与进展中的作用。方法　用逆转录聚合酶链反应 (RT PCR)测定了 3 5例膀胱移行细胞癌和 6例正常膀胱黏膜的PD ECGFmRNA水平 ;用NIHImage软件量化分析目标PCR条带的面积与吸光度。结果　膀胱癌的PD ECGFmRNA表达水平是正常膀胱黏膜的 3 .86倍 (t =2 .3 6,P <0 .0 5) ,其中Ta、T1与T2 4期肿瘤分别是正常膀胱黏膜的 1.3 3倍、4.0 2倍和 7.59倍 ,G3级肿瘤的PD ECGFmRNA表达水平是G1 2级肿瘤的 2 .2 7倍 (t =3 .52 ,P <0 .0 1) ,G1 2级肿瘤是正常膀胱黏膜的 2 .3 9倍 (t =2 .0 7,P <0 .0 5)。结论　PD ECGFmRNA表达水平与膀胱移行细胞癌的浸润深度与分级呈正相关 ,PD ECGFmRNA表达水平对判断膀胱移行细胞癌的侵袭性及临床上制定治疗方案有重要意义     

Correlation between microvessel density and tumor cell proliferation with clinical factors in breast carcinomas.

Fifty-nine methacarn-fixed, paraffin-embedded human breast carcinomas were immunostained by QB-END/10 (an antibody to CD34 antigen) to observe microvessels and by PC10 (an antibody to proliferating cell nuclear antigen; PCNA) to determine tumor cell proliferation; 9 normal human breast tissue specimens were also immunostained by QB-END/10. The number of microvessels in the periphery of the breast carcinoma was significantly greater than both that in the center of the breast carcinoma and that in the normal breast. There was also a significant relationship between the number of microvessels in the periphery of breast carcinomas and the histological tumor size and lymph node status. However, there was no significant relationship between the tumor cell proliferation activity (PCNA positive cell ratio) and any clinical or histopathological variables. The number of microvessels and the tumor cell proliferation activity showed a weak negative correlation.     

罕见浆细胞样移行细胞癌的病理临床研究(英文)

目的总结并探讨膀胱浆细胞样移行细胞癌的病理特征、诊断和鉴别诊断及临床特点。方法采用常规HE、巴氏染色和免疫组化方法(S-P方法),光镜观察2例膀胱浆细胞样移行细胞癌,通过临床随访和文献复习对此罕见膀胱肿瘤进行讨论。结果其特点是除粘膜有原位癌外,肿瘤多侵犯固有膜和／或肌层。细胞形态和浆细胞相似。肿瘤细胞高表达AEI／AE3,CEA和CK18。临床预后较一般的移行细胞癌差。结论膀胱浆细胞样移行细胞癌罕见,具有其特有的组织病理学和生物学特点,诊断膀胱肿瘤时应考虑到该肿瘤的可能性。     

K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa

The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas. K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69 (6%) of transitional mucosa samples, but not in the normal mucosa. Further, mutation rates were increased in younger patients (P = 0.001) and in mucinous carcinomas (50%) compared with well differentiated (17%), moderately differentiated (26%) or poorly differentiated (24%) tumours. Our findings indicate that mucinous carcinoma may represent a distinct genetic entity.     

Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue

In humans, most blood group substances (BGS) are expressed throughout the fetal colon but are absent from the distal portion of adult colon. Cancers of the distal colon frequently reexpress BGS thereby suggesting that these antigens behave as oncofetal antigens at this organ site. We used a sensitive immunoperoxidase method with monoclonal antibodies directed against blood groups A, B, O (H), Lewisa and Lewisb to systematically evaluate BGS expression in fetal colon, normal adult colon from immediate autopsies of kidney donors, mucosa adjacent to cancer (transitional mucosa) and colorectal cancer tissues. In normal colon, BG-A, B, H, and Lewisb were expressed in proximal but not distal colon, whereas Lewisa was distributed uniformly throughout the colon. In colon cancer, and fetal colon, the proximal-distal gradient of BG-A, B, H, and Lewisb expression was abolished because of enhanced distal expression of these antigens. In cancer tissues, three patterns of altered BGS expression emerged: (a) incompatible expression of BG-A or BG-B (over 50% of patients); (b) deletion of BGS; and (c) precursor BG-H accumulation (80% of 25 tumors). BGS staining of transitional mucosa closely resembled that of the adjacent tumor except that no examples of BGS deletion were encountered in transitional mucosa. The goblet cell secretory vacuole accounted for most of the BGS expression in normal colon, but cancer cells demonstrated differentiation-dependent antigenic expression such that well-differentiated tumors expressed BGS on cell apical membranes and glandular contents, but poorly differentiated cancers exhibited diffuse cytoplasmic staining. These findings confirm the oncofetal nature of BGS in distal colon cancer, and provide immunohistochemical evidence for a diverse repertoire of altered antigen expression in colon cancer. Further investigation is needed to elucidate the possible genetic and biochemical mechanisms involved.     

Bladder wall permeability to to topically administered cisplatin

The aim of the study was quantitation of cisplatinum in the wall of normal urinary bladder, tumor tissue, inflamed mucosa and blood in intravesical administration of cisplatinum. The samples of the tissue were radiated in the flow of heat neutrons 5 x 10(12)-5 x 10(13) neut/cm followed by radiochemical purification of the material and platinum assay in the tissue using analyser LP-4900 with semiconductor radiation detector. The samples were taken from 32 patients with transitional cancer of the bladder. Tumor tissue contained platinum in amounts 33.7 times exceeding those in normal tissue after intravesical administration of 100 mg of the drug. After intravenous administration of 100 mg cisplatinum normal bladder tissue and tumor tissue contained almost similar quantities of the drug. Thus, tumor tissue absorbs more cisplatinum than normal tissue of the bladder in intravesical administration.     

P33ING1、p53在膀胱移行细胞癌中的表达及与细胞凋亡的相关性

目的：探讨抑癌基因P33ING1在膀胱移行细胞癌（BTCC）中的表达及其与p53蛋白表达及细胞凋亡的相关性。方法：利用免疫组化S-P法和TUNEL法检测83例BTCC及11例正常膀胱黏膜组织P33ING1、p53的表达及细胞凋亡指数（AI）。结果：83例膀胱移行细胞癌组织中,P33ING1蛋白的阳性表达率为59.03%,而正常膀胱黏膜组织中P33ING1蛋白阳性表达率为90.9%。P33ING1蛋白表达与膀胱移行细胞癌的WHO肿瘤分级有相关性。Spearman相关分析表明P33ING1蛋白表达与p53蛋白表达正相关（P〈0.05）。AI与P33ING1及p53蛋白表达无相关性。结论：P33ING1在膀胱移行细胞癌中表达下降可能在膀胱移行细胞癌的发生、发展过程中起重要作用,P33ING1与p53基因具有协同作用,同时检测p53的状态和P33ING1表达水平,对于膀胱癌的诊断、治疗和预后判断可能具有积极意义。