大肠腺瘤与腺癌P21,P53,P185蛋白表达及ras,p53基因突变的检测

应用免疫组化及ＰＣＲ－ＲＦＬＰ法检测３０例大肠腺瘤、７４例大肠腺癌及癌旁粘膜Ｐ２１、Ｐ５３、Ｐ１８５蛋白表达及ｒａｓ、ｐ５３基因突变。结果表明，大肠腺瘤Ｐ２１、Ｐ５３蛋白阳性率（５３．３％，２７．６％）高于癌旁粘膜（Ｐ＜０．０１），二者过度表达与腺瘤恶性倾向有关。大肠腺癌Ｐ２１、Ｐ５３及Ｐ１８５蛋白阳性率（７２．９％，３７．８％，４７．２％）皆高于腺瘤Ｉ级不典型增生（Ｐ＜０．０１，Ｐ＜０．０５及Ｐ＜０．０５）。９例腺瘤，４０例腺癌存在两种以上蛋白表达，共同表达与腺瘤恶性倾向及腺癌预后有关。大肠腺瘤及腺癌ｒａｓ基因突变率分别为２６．７％及４１．９％，ｒａｓ基因突变与腺瘤恶性倾向有关。大肠腺瘤及腺癌ｐ５３基因２４８位点突变率分别为３．３％及１４．９％。６例腺癌存在两种基因突变，两种基因协同突变与大肠癌预后有关。提示ｒａｓ、ｐ５３及ｃ－ｅｒｂＢ－２基因改变均参与了大肠癌的发生、发展过程。     

c—erbB—2表达及DNA含量与乳腺癌组织学类型的相关性研究

目的：了解乳腺癌组织学类型与ｃ－ｅｒｂＢ－２表达和ＤＮＡ异倍体的关系。方法：用免疫组化法（ＬＳＡＢ），经典的Ｆｅｕｌｇｅｎ染色法及图像分析技术对８４例乳腺癌，２２例乳腺良性病变进行ｃ－ｅｒｂＢ－２免疫组化及ＤＮＡ含量检测。结果：（１）乳腺良性病变全部为整倍体，ｃ－ｅｒｂＢ－２表达阴性。乳腺癌异倍体７０．２％，ｃ－ｅｒｂＢ－２阳性表达率为３３％。（２）浸润性导管癌ｃ－ｅｒｂＢ－２阳性表达率（４１．６％）、异倍体比例（７７％）均高于特殊类型浸润癌（９．６％和５４．８％）。而Ｐａｇｅｔ病阳性表达率和异倍体比例最高（分别为１００％和８０％）。（３）浸润性导管癌ｃ－ｅｒｂＢ－２表达率随合并导管原位癌成分或合并明显坏死而增高（Ｐ＜０．０５）。粉刺型占优势，其表达率高于非粉刺型（Ｐ＜０．０５）。（４）ｃ－ｅｒｂＢ－２阳性肿瘤异倍体高于ｃ－ｅｒｂＢ－２阴性肿瘤异倍体（Ｐ＜０．０５）。结论：ｃ－ｅｒｂＢ－２激活和异倍体的出现主要与导管上皮细胞异型增生有关。可作为乳腺癌一个特殊亚群的诊断依据     

胃癌组织HLA－I类和DR分子免疫组化研究

本文应用免疫组化法对６４例胃癌、癌旁组织和６例胃溃疡大致正常胃粘膜冰冻和石蜡切片进行了染色．结果表明，正常胃粘膜和癌旁胃粘膜上皮细胞ＨＬＡ－Ｉ类分子表达阳性，其着色较均一，ＨＬＡ－ＤＲ染色均阴性．胃癌细胞Ｉ类分子表达缺失（２７／６４例），与癌旁上皮比较差异显著（Ｐ＜０．０１）。粘液细胞癌和低分化癌Ｉ类分子缺失率显著高于高分化癌（Ｐ＜０．０２５）．此外，发生肿瘤转移的病例Ｉ类分子缺失率（１２／１５例）显著高于无转移组（１／５例，Ｐ＜０．０２５）．ＤＲ分子在癌组织表达阳性，其阳性率高达５３．１％（３４／６４例）．低分化癌ＤＲ分子阳性率亦显著高于高分化癌和中分化癌，未分化癌ＤＲ分子阳性率亦显著高于高分化癌（Ｐ＜０．０１～０．０５）．提示（１）ＨＬＡ－Ｉ类分子表达缺失可能与癌细胞逃避宿主免疫监视发生润浸生长和转移有关；（２）分化程度不同的癌组织ＨＬＡ－Ｉ类分子表达差异显著，提示癌细胞分化可能影响Ｉ、Ⅱ类分子表达和肿癌抗原呈递；（３）ＨＬＡ－Ｉ类和ＤＲ分子表达异常可能是上皮恶性转变的标志之一．     

人肝癌与癌旁肝AFP阳性细胞形态的图象分析及增殖活性的研究

采用免疫组化、双标免疫组化及图象分析技术，研究了２７例人体肝细胞癌与癌旁肝甲胎蛋白（ＡＦＰ）阳性细胞的量化形态特征及以其增殖细胞核抗原（ＰＣＮＡ）标记率显示的增殖活性。主要结果显示：（１）ＡＦＰ阳性与阴性癌及癌旁近癌肝细胞间难以用量化形态标准区分（Ｐ＞０．０５）；核面积与核浆比提示癌旁ＡＦＰ阳性肝细胞可能是尚无表型转化的癌前细胞。（２）ＡＦＰ阳性癌细胞ＰＣＮＡ的平均标记率（１５．７０％±６．２５％）显著低于肝癌的平均标记率（Ｐ＜０．０１），表明大多数ＡＦＰ阳性癌细胞处于非增殖状态。（３）癌旁近癌肝可见ＡＦＰ与ＰＣＮＡ双标阳性肝细胞。     

严重烧伤病人感染期恢复阶段的微循环改变

目的探索严重烧伤病人感染恢复阶段的微循环改变。方法用微循环显微镜（ＷＸ－７５３Ｂ型）及其图像处理系统（ＸＧ－８型），观测５１例处于烧伤感染恢复阶段的严重烧伤病人足甲襞微循环。本组平均烧伤面积是５４．５９％±１７．３０％，年龄为２７．２１±５．２７岁；对照组是５０例健康成人，年龄为２４．４０±４．６８岁。结果与对照组比较，感染恢复组管襻畸形发生率明显高于对照组（Ｐ<０．０１）；血流速度慢（Ｐ<０．０５），红细胞聚集性增高（Ｐ＜０．０１），聚集以轻、中度为主；血管襻周围有轻度渗出（Ｐ<０．０１），汗腺导管数减少（Ｐ<０．０１），其余指标无显著性变化（Ｐ>０．０５）。结论感染恢复阶段的严重烧伤病人存在一定程度的微循环障碍，在治疗时需纠正微循环紊乱。     

c—erbB—2,AgNOR在乳腺癌中的预后价值及其相互关系探讨

对８８例乳腺癌作了ＡｇＮＯＲ银染计数及ｃ－ｅｒｂＢ －２癌蛋白的免疫组化研究。结果发现ｃ－ｅｒｂＢ－２阳性者，病死率大于ｃ－ｅｒｂＢ－２阴性者（Ｐ＜０．０１）；ＡｇＮＯＲ计数＞５者，病死记大于ＡｇＮＯＲ≤５者（Ｐ＜０．０１），表明了这两个指标对预后具有明显的价值。同时发现ＡｇＮＯＲ值＜４者，ｃ－ｅｒｂＢ－２阳性率显著高于ＡｇＮＯＲ≤４者（Ｐ＜０．０５），表明这两个指标之间有一定的关系。我们还发现     

宫颈癌细胞增殖及凋亡与bcl-2表达的研究

本研究旨在探求宫颈癌变中细胞增殖和细胞凋亡的变化规律,以及凋亡出现频率与ｂｃｌ－２癌蛋白的关系。结果发现宫颈癌组织的增殖指数（ＰＩ）和凋亡指数（ＡＩ）明显高于正常宫颈组织和宫颈不典型增生组织（Ｐ＜０．０１）,而ＡＩ／ＰＩ显著低于两者（Ｐ＜０．０１）。ｂｃｌ－２癌蛋白常见于正常宫颈上皮和不典型增生上皮的基底细胞层,宫颈癌组织中其表达随临床期别升高呈下降趋势,ｂｃｌ－２阳性组的ＡＩ与阴性组无显著差异。证实宫颈癌变是细胞无限增殖,凋亡异常被抑制的结果。ｂｃｌ－２是宫颈癌变的早期特征,但不是调节细胞凋亡的唯一因素     

p53、EGFR和Ki-67抗原在子宫恶性中胚叶混合瘤中的表达

目的：研究子宫恶性中胚叶混合瘤ｐ５３、ＥＧＦＲ和Ｋｉ－６７抗原的表达及与肿瘤临床分期、组织学分级和预后的关系。方法：用免疫组化Ｓ－Ｐ法对２１例子宫恶性中胚叶混合瘤的存档资料作染色观察。结果：ｐ５３、ＥＧＦＲ和Ｋｉ－６７抗原的阳性表达率分别为６１．９％、６１．９％和７１．４％。临床分期Ⅱ～Ⅳ期肿瘤（１０／１２）的ｐ５３阳性表达率明显高于Ⅰ期肿瘤（３／９）（Ｐ＜０．０５）、肿瘤癌性成分Ⅱ级的ｐ５３阳性表达高于Ⅰ期（Ｐ＜０．０５）。６例在１年内死亡的病例，其中５例ｐ５３阳性染色，而５例生存２年以上的肿瘤ｐ５３免疫染色全部阴性，两组比较（Ｐ＜０．０５）。肉瘤成分Ⅲ级的ＥＧＦＲ阳性率高于Ⅱ级（Ｐ＜０．０５），除此而外，ＥＧＦＲ和Ｋｉ－６７的表达和肿瘤分期、预后均无相关性。结论：肿瘤的ｐ５３表达具有预后意义     

青年人大肠癌细胞p53蛋白表达和DNA的定量研究

目的：研究青年人大肠癌抑癌基因ｐ５３蛋白的表达和细胞ＤＮＡ含量。方法：采用流式细胞光度术（ＦＣＭ）。结果：青年组大肠癌细胞ＤＩ值（１．３０±０．１７）显著大于老年癌组（１．１０±０．０９）（Ｐ＜０．０１），且细胞增殖指数（ＰＩ）亦明显大于后者（２４．９％±６．５％ｖｓ２０．２％±４．７％）（Ｐ＜０．０５）。青年组大肠癌中ＤＮＡ异倍体癌发生率为８７．１％（２７／３１），而老年癌组仅为２８．６％（４／１４），两者之间差别有高度显著性（Ｐ＜０．００１）。ｐ５３蛋白表达量青年患者（ＦＩ＝１．３４±０．２６）显著大于老年患者（ＦＩ＝１．１５±０．２５）（Ｐ＜０．０１）。在青年大肠癌中，粘液癌和侵犯周围软组织者，其ｐ５３蛋白的阳性表达率（１００％，９５％）分别高于腺癌和浸润较浅者（６７％，５８％）（Ｐ＜０．０５），而且低分化癌和有局部淋巴转移者ｐ５３蛋白的表达阳性率（９３％，１００％）也较高、中分化癌和无局部淋巴结转移者（６９％，６８％）为高。结论：在ＤＮＡ水平上，青年大肠癌的恶性程度高于老年大肠癌；ｐ５３蛋白的高表达可能是造成青年大肠癌恶性度高的原因之一。     

慢性肾炎患者血清sIL－2R和IL－8的变化及意义

研究用ＥＬＩＳＡ双抗体夹心法对慢性肾炎肾功能不全各期患者血清ｓＩＬ－２Ｒ和ＩＬ－８水平进行了测定。结果显示：①肾功能不全代偿期ｓＩＬ－２Ｒ水平显著高于健康人（Ｐ＜０．０１），提示此期存在Ｔ细胞异常活化。②氮质血症期ｓＩＬ－２Ｒ水平显著高于健康人和代偿期（Ｐ＜０．０１），与Ｓｃｒ呈显著正相关（ｒ＝０．６５，Ｐ＜０．０００５），提示血清ｓＩＬ－２Ｒ水平可作为肾小球肾炎恶化的重要指标。③尿毒症期ＩＬ－８水平显著低于健康人（Ｐ＜０．０１），ｓＩＬ－２Ｒ水平显著低于氮质血症期（Ｐ＜０．０１），提示此期存在细胞免疫缺陷，其中单核细胞缺陷可能是Ｔ细胞功能低下的重要原因；ＩＬ－８水平降低可能是此期中性粒细胞吞噬功能减弱的原因之一。总之，本研究有助于进一步阐明慢性肾炎的发病机理。     

乳腺癌癌旁腺病的病理形态观察

从病理形态学角度研究了本院142例乳腺癌并存癌旁腺病的改变,并重点观察乳腺癌癌旁腺病性上皮增生、不典型增生与癌的关系。发现:全组95%以上腺病性导管上皮出现不典型增生;40.1%显示增生、不典型增生与癌的移行形态;11.3%发现腺病性小叶内上皮多中心癌变灶。由此提出腺病(尤其当出现导管上皮重度增生、不典型增生时)与乳腺癌发生有直接关系,应引起临床重视和慎重处理。     

Small focal lesions of the breast: a clinico-morphological analysis

Morphological and mammographic study of small (less than 1 cm) focal mammary gland lesions of 170 women revealed foci of typical epithelium proliferation of the ducts and lobules, fibrosing adenosis, small duct papillomas and fibroadenoma, intraductal and ductal carcinoma in situ, sometimes with small invasion foci, infiltrating carcinoma, infiltrating lobular carcinoma. Peculiarities of small focal lesion morphology determine the mammographic picture. Analysis of nodular shadows on the mammogram gives as a rule a possibility to differentiate between benign conditions (focal proliferation of the epithelium, fibroadenoma), early carcinoma (intraductal and lobular in situ, sometimes with small foci of invasion) and infiltrating carcinoma. Calcareous deposits in both benign lesions and carcinomas do not differ mammographically. Morphogenetic link was revealed between foci of epithelium proliferation (benign displasia), intraductal and lobular carcinoma in situ and infiltrating carcinoma. Among 65 cases of non-palpable carcinoma, 31 (47.7%) were classified as early carcinoma and 34 (52.3%) as infiltrating carcinoma with a relatively low histological degree of malignancy. In both groups a good postoperative survival was observed.     

Carcinoma in situ involving sclerosing adenosis: a mimic of invasive breast carcinoma

The distinction between invasive and in situ carcinoma of the breast is important with regard to the treatment and prognosis of the patient. When carcinoma in situ involves breast tissue in which the normal architecture is altered by pre-existing sclerosing adenosis, the resulting histological picture may closely mimic an invasive carcinoma. We record the histopathological features in 13 cases where there was difficulty in identifying the presence or extent of invasive carcinoma. The most useful clue was attention to the low power appearances of distorted lobular units in the areas of malignancy and comparison with surrounding breast tissue which usually showed recognizable sclerosing adenosis. The use of immunohistochemical stains for myoepithelium (α-actin and S-100 protein) and for basement membrane (collagen type IV and laminin) proved to be of considerable value in identifying the preservation of these features around glandular structures in areas of sclerosing adenosis containing in situ carcinoma.     

Expression of c-erbB2, p53, Bcl-2, Bax,c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast

Molecular evidence has recently suggested a number of different pathways leading to the development of ductal carcinoma of the breast. The links between atypical ductal hyperplasia and low-grade ductal carcinoma in situ and lobular neoplasia and lobular carcinoma are well known pathologically, but high-grade in situ and invasive carcinomas appear to have a different biological oncogenetic pathway. Morphologically there is a similarity between apocrine cells and some cases of high-grade ductal carcinoma. In order to investigate this possibility a number of different biological markers known to occur in high-grade breast carcinomas were assessed in both apocrine metaplasia (APM) and a putative premalignant lesion called apocrine change within sclerosing adenosis (AA). In 64 cases of APM and 18 cases of AA we examined for expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 proteins using immunocytochemistry. c-erbB2 expression was seen in 55.6% of AA cases and in 10.9% of APM cases. p53 expression was detected in 27.8% of AA cases but only 1.6% of APM cases. All cases of AA and APM were negative for the anti-apoptotic protein Bcl-2, but all the APM and 33.3% of AA cases showed cytoplasmic positivity for Bax, a pro-apoptotic protein. All the cases of AA and APM were positive for c-myc oncoprotein, however, the mean percentage of nuclear positivity was 50% in AA and 37% in cases of APM cases. The mean percentage positivity for Ki-67, a proliferation associated antigen, was 3.6% in AA and 1.3% in APM. The results indicate that a subset of breast lesions containing APM epithelium show abnormal oncoprotein and apoptosis-related protein expression and have a higher proliferation rate.     

Twist转录因子、E-钙黏蛋白和N-钙黏蛋白在乳腺癌中的表达及意义

目的 观察上皮间质转化因子Twist转录因子(简称Twist)和相关蛋白E-和N-钙黏蛋白(cadherin)在乳腺癌中的表达及其与患者临床病理指标的关系.方法 采用免疫组织化学SP法检测56例浸润性导管癌、38例浸润性小叶癌和41例导管内癌以及10例正常乳腺组织中Twist、E-和N-cadherin的表达.结果 (1)三种病理类型乳腺癌组织中,Twist阳性率分别为46.4%(26/56)、79.0%(30/38)和26.8%(11/41),其中浸润性小叶癌中Twist阳性率显著高于浸润性导管癌和导管内癌(分别P=0.002、0.000);E-cadherin阳性率分别为78.6%(44/56)、29.0%(11/38)和80.5%(33/41),其中浸润性导管癌和导管内癌中E-cadherin阳性率显著高于浸润性小叶癌(均P=0.000);N-cadherin阳性率分别为53.6%(30/56)、68.4%(30/56)和31.7%(13/41),其中在浸润性导管癌和浸润性小叶癌中的阳性表达显著高于导管内癌(分别P=0.033、0.001).(2)135例乳腺癌组织中Twist和E-cadherin表达呈显著负相关性(P=0.005,Spearman相关系数-0.239);Twist和N-cadherin 表达呈显著正相关性(P=0.000,Spearman相关系数0.319).(3)乳腺浸润性导管癌差分化组中N-cadherin阳性率显著高于中分化和高分化组(P=0.004).(4)乳腺浸润性小叶癌淋巴结转移组中Twist阳性率显著高于淋巴结未转移组(P=0.037).结论 三种蛋白在三种乳腺癌组织中的表达差异较大.Twist阳性表达与乳腺浸润性小叶癌淋巴结转移相关.N-cadherin阳性率与乳腺浸润性导管癌组织学分级相关.检测这三个指标可为研究乳腺癌的进展和转移机制及评判其生物学行为提供有价值的参考.     

结直肠癌临床及病理免疫组织化学多因素分析

目的探讨结直肠癌的生长方式,间质淋巴细胞浸润,Ｄｕｋｅｓ分期,ｐ５３和ｃ－ｅｒｂＢ－２蛋白,增殖细胞核抗原（ＰＣＮＡ）增殖指数,Ｐ２１蛋白,上皮生长因子受体（ＥＧＦＲ）、间质纤维组织增生及组织学类型１０种因素对患者预后的影响。方法运用Ｃｏｘ模型对６８例结直肠癌上述十种因素与预后的关系进行分析。结果单因素分析显示上述前六种因素对患者的预后有影响;经多因素分析显示Ｐ２１和ｃ－ｅｒｂＢ－２蛋白表达情况,Ｄｕｋｅｓ分期以及ＰＣＮＡ指数与病人预后有关,两种癌基因蛋白共同表达时病人的死亡相对危险度更高,ＤｕｋｅｓＡ期Ｐ２１或ｃ－ｅｒｂＢ－２蛋白阳性病人的死亡相对危险度比ＤｕｋｅｓＢ期相应蛋白阴性的病人高。结论Ｐ２１、ｃ－ｅｒｂＢ－２蛋白、ＰＣＮＡ增殖指数及Ｄｕｋｅｓ分期可作为估计结直肠癌患者预后的独立指标,Ｐ２１及ｃ－ｅｒｂＢ－２蛋白同时表达是预后更差的指征。     

Lobular carcinoma in situ in sclerosing adenosis

The initial presentation of breast malignancy as noninvasive carcinoma in an area of sclerosing adenosis is unusual. Especially, lobular carcinoma in situ in sclerosing adenosis sometimes can be a potential source of confusion with invasive lobular carcinoma. We report a case of lobular carcinoma in situ presenting in adenosis exhibiting patterns akin to invasive lobular carcinoma, thus leading to potential misdiagnosis. Overall architecture of the lesion as seen at lower power and immunohistochemistry can be useful to distinguish between sclerosing adenosis with lobular carcinoma in situ and infiltrating lobular carcinoma.     

Intraductal carcinoma of the breast arising in sclerosing adenosis

An unusual case of intraductal carcinoma of the breast arising in sclerosing adenosis is reported. A 49 year old Japanese woman noticed a lump in her right breast 3 years before she sought medical advice. Histologic examination of the lumpectomy specimen showed, adjacent to intraductal papilloma, sclerosing adenosis involved in a neoplastic cellular proliferation with cribriform pattern and comedo necrosis. lmmunohistochemical study with antl-actin antibodies discriminated intraductal carcinoma from adjacent sclerosing adenosis by highlighting myoepithelial components in the latter. Extensive sampling revealed no carcinoma outside the sclerosing adenosis, implying that the intraductal carcinoma did originate in the tubules of sclerosing adenosis. A review of the literature indicated that the ductal to lobular ratio among carcinoma in situ concurring with sclerosing adenosis is about 1:2. The average age of patients with ductal and lobular carcinoma in situ in sclerosing adenosis is 39 and 43.7, respectively. It is suggested that carcinoma in situ arising in sclerosing adenosis and fibroadenoma have a similar biological basis.     

肿瘤相关抗原LEA在大肠癌及大肠非癌患者血清中的表达

目的　探讨LEA在大肠腺瘤和大肠癌的早期诊断价值。方法　应用双抗夹心ELLSA技术 ,以ND - 1单抗和抗CEA单体分别对大肠癌患者 93例、大肠腺瘤 16例、炎性息肉 15例及正常人 32例的血清进行LEA和CEA的检测。结果　LEA在大肠癌的阳性表达率为 72 %与炎性息肉的 7%存在非常显著性关系(P <0 0 1) ;CEA在大肠癌的阳性表达率为 5 9%与健康人的 6 %也存在非常显著性差异 (P <0 0 1)。但LEA在大肠腺瘤的阳性表达率为 6 3%与炎性息肉的 7%存在非常显著性差异 (P <0 0 1) ,而CEA的大肠腺瘤与炎性息肉分别为 5 0 %和 7% ,无显著性差异 (P >0 0 5 )。结论　LEA在大肠腺瘤的血清学表达很有可能作为大肠癌前病变的指标