前列腺癌P504S、p63及CK34βE12表达的研究

目的：探讨P504S、p63及CK34βE12表达在前列腺癌诊断和鉴别诊断中的价值。方法：采用免疫组织化学技术，检测P504S、p63及CK34βE12在各类前列腺病变中的表达。结果：102例前列腺癌中有92例表达P504S（90．2％）；P504S在良性前列腺病变上皮中表达率是8．2％（8／97），在前列腺高级别上皮内瘤（high grade intraepithelial neoplasias，HGPIN）中表达率是39．5％（15／38）。在切除的前列腺良性标本中，有〉2个腺体的p63表达缺失例数发生率为28．8％，明显低于CK34βE12的发生率53．0％（P〈0．05）。结论：P504S是前列腺癌敏感的生物学标志物；p63在前列腺基底细胞表达完整性方面优于CK34βE12；P504S和基底细胞标志物在临床病理诊断中联合应用可达到互补的作用。     

非小细胞肺癌微转移分子标志物表达的研究

目的探讨非小细胞肺癌（NSCLC）患者外周血癌胚抗原（CEA）、细胞角蛋白19片段（CK19）、外周血肺组织特异性基因（Lunx）mRNA表达对于肿瘤微转移的诊断价值。方法采用反转录一聚合酶链反应（RT—PCR）技术,对46例NSCLC患者及18例良性肺部疾病患者外周血CEA、CK19、LunxmRNA进行检测。结果NSCLC患者外周血Lunx、CEA、CK19的mRNA表达阳性率为52．2％（24例）、43．5％（20例）、41．3％（19例）,其中I、Ⅱ、Ⅲ、Ⅳ期NSCLC患者LunxmRNA阳性率为16．6％（1／6）、44．4％（4／9）、50．0％（7／14）、70．6％（12／17）,CEAmRNA阳性率为16．6％（1／6）、33_3％（3／9）、50．0％（7／14）、52．9％（9／17）,CKl9mRNA阳性率为0（0／6）、22．2％（2／9）、42．9％（6／14）、64．7％（11／17）,与对照组比较差异均有统计学意义（Fisher精确概率法,P〈0．05）。结论外周血CEA、CKl9、LunxmRNA表达可作为诊断早期NSCLC患者肿瘤微转移的重要参考指标。     

胆囊原发性腺鳞癌一例临床病理分析并文献复习

目的：分析胆囊原发性腺鳞癌的临床病理特点、鉴别诊断及治疗预后.方法：对1例胆囊腺鳞癌的临床资料进行分析,并复习相关文献.结果：本病早期无特异临床表现,主要表现为右上腹疼痛合并胆囊内结石.组织学特点：肿瘤由鳞癌及腺癌两种成分构成.以鳞癌成分为主呈巢状结构,鳞癌细胞大小不等,异型性明显,胞浆丰富,边界清楚,核仁较明显,核分裂像可见,可见角化珠、单个细胞内角化及细胞间桥.腺癌成分较少,肿瘤细胞排列成不规则的腺体,异型性较明显.间质中淋巴细胞较丰富,部分腺癌与鳞癌间质有移行.免疫组化染色显示：部分癌细胞34βE12（＋＋）,部分癌细胞CK7（＋＋）、CEA（＋）、CA19-9（＋＋）、ki-67（＋）、p53（＋）、CK20（-）.结论：胆囊腺鳞癌是一种少见的胆囊肿瘤,其诊断主要依靠组织病理学和免疫组化标记.     

免疫组化在前列腺癌诊断中的作用

目的观察p504S、p63、CK34βE12在前列腺癌诊断和鉴别诊断中的价值.方法用免疫组化S-P法检测p504S、p63、CK34βE12在前列腺癌、PIN和前列腺良性增生中的表达.结果 72例前列腺癌中61例p504S阳性,但p63和CK34βE12大部分阴性.6例PIN中5例p504S阳性,但p63和CK34βE12均阳性.而良性增生表现为p504S阴性,p63和CK34βE12阳性.结论 p504S和p63、CK34βE12联合检测可极大地提高前列腺癌诊断的准确率.     

CK34βE12、p63和P504S联合检测在前列腺癌诊断中的应用

 目的 探讨CK34βE12、p63和P504S联合免疫组化标记在前列腺良、恶性病变鉴别诊断中的应用价值。方法 应用免疫组织化学方法，观察74例前列腺病变标本[包括前列腺癌（PC）27例、高级别前列腺上皮内瘤（HGPIN）6例、低级别前列腺上皮内瘤（LGPIN）10例、前列腺非典型腺瘤性增生（AAH）3例、良性前列腺增生（BPH）28例]中CK34βE12、p63和P504S的表达情况。结果 p63和CK34βE12在AAH、LGPIN和BPH中均为阳性染色，而在PC中均为阴性，在6例HGPIN中5例为阳性，PC组表达率明显低于其他病变组差异有统计学意义（P＜0.01）；P504S 在PC、AAH、HGPIN、LGPIN和BPH中阳性率分别为92.6 %（25／27）、0、66.7 %、10 %和0，PC组明显高于AAH、LGPIN和BPH组（P＜0.01），与HGPIN组之间差异无统计学意义（P = 0.132）；P504S阳性协同p63或CK34βE12阴性两种标记在PC、AAH、HGPIN、LGPIN和BPH中表达率分别为92.6 %、0、16.7 %、0和0，两种标记表达在前列腺癌与其他病变之间差异有统计学意义（P＜0.01）。结论 利用P504S与p63或CK34βE12联合检测有助于提高前列腺癌诊断的准确率。     

基底细胞样乳腺癌免疫组化特征及其意义

[目的]探讨基底细胞样乳腺癌（BLBC）的免疫组化特征及其意义。[方法]采用免疫组化检测46例BLBC中细胞角蛋白、肌上皮标记以及EGFR、p53、ERCCl、cKit和Ki67的表达,并通过与激素受体阳性乳腺癌（HR^＋乳腺癌）的比较,分析BLBC免疫组化特点。[结果]58．7％和43．5％BLBC组织中分别表达高分子角蛋白CK5／6和CK14。32．6％、13．0％、15．2％和15．2％BLBC分别表达肌上皮标记SMA、p63、CD10和S100。高分子角蛋白和肌上皮标记表达率均高于HR^＋乳腺癌。BLBC中Vimentin、p53和Ki67阳性率分别为45．7％、60．9％和43．5％,均高于HR^＋乳腺癌。EGFR、ERCCl和cKit阳性率分别为65．2％、34．8％和30．4％,与HR^＋乳腺癌比较差异均有统计学意义。[结论]BLBC是一组可表达高分子角蛋白及肌上皮标记、细胞增殖活跃和具有侵袭倾向的乳腺癌。EGFR和ERCCl检测可用于指导临床治疗。     

肺鳞状细胞癌组织中p63、CK5/6和p40的表达及其病理诊断价值

目的:探讨p63蛋白、细胞角蛋白5/6（cytokeratin5/6,CK5/6）和p40（ΔNp63）蛋白在人非小细胞肺癌（non-small cell lung cancer,NSCLC）组织中的表达及其表达对于肺鳞状细胞癌和肺腺癌的诊断和鉴别诊断价值。方法:采用免疫组化（SP法）检测p63、CK5/6和p40在100例病理确诊的NSCLC组织中的表达情况,并结合NSCLC的临床病理特征进行分析。结果:p63、CK5/6和p40在肺鳞状细胞癌组织中的阳性表达率分别为98.28%、100.00%和98.28%。p63、CK5/6和p40在肺腺癌组织中的阳性表达率分别为45.24%、30.95%和21.43%。肺鳞状细胞癌组织中p63、CK5/6和p40的阳性表达率明显高于肺腺癌组织（P<0.01）。p63、CK5/6和p40诊断肺鳞癌的灵敏度分别为98.28%、100.00%和98.28%,特异度分别为54.76%、69.05%和78.57%。p63、CK5/6和p40在肺鳞状细胞癌中的诊断准确率分别为80%、87%和90%。三者联合检测时三项均阳性诊断肺鳞癌的特异度达90.48%,诊断准确率为95%;三项中至少一项阳性诊断肺鳞癌的灵敏度达100.00%,诊断准确率为75%。结论:p63、CK5/6和p40主要表达在肺鳞状细胞癌组织中。单个指标中p40对诊断肺鳞状细胞癌具有较高的灵敏度和特异度。p63、CK5/6和p40联合检测对肺鳞状细胞癌与肺腺癌的鉴别诊断有重要价值。     

CEA、NSE、CYFRA21-1联合检测肺癌的临床意义

[目的]探讨外周血肿瘤标志物癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19（CYFRA21-1）单项和联合检测对肺癌诊断的价值。[方法]采用酶联免疫法检测35例肺癌患者、20例健康人和32例肺部良性疾病患者血清中3种肿瘤标志物的水平，同时对32例患者进行治疗前后标志物水平检测。[结果]肺癌患者CEA、NSE、CYFRA21-1血清水平明显高于肺良性疾患和健康人，有显著性差异（P〈0．01）；3种标志物在肺癌不同病理类型中比较均有差异，其中腺癌CEA阳性率81．8％、小细胞肺癌NSE阳性率87．5％、鳞癌CYFRA21-1阳性率81．3％．高于其他类型（P〈0．05），三项联合检测阳性率可达94.3％，灵敏度92．8％，特异度95．2％；治疗有效的肺癌患者3种标志物水平均明显下降，而治疗无效者治疗前后均无明显变化。[结论]CEA、NSE、CYFRA21-1联合检测可明显提高肺癌的阳性检出率。     

34βE12、CK5/6、p63、SMA在乳腺增生、不典型增生与原位癌鉴别诊断中的价值

目的探讨高分子量细胞角蛋白34βE12、细胞角蛋白CK5/6、肌上皮标记物p63、平滑肌肌动蛋白SMA在乳腺增生、不典型增生与原位癌鉴别诊断中的价值。方法采用免疫组织化学染色法(SP),检测34βE12、CK5/6、p63、SMA在30例乳腺普通型增生(UDH)、30例非典型导管增生(ADH)、20例导管原位癌(DCIS)和20例浸润性导管癌(IDC)中的表达。结果 UDH和ADH组中34βE12均呈阳性表达,DCIS和IDC组中大部分34βE12呈阴性表达,前两组与后两组比较,差异均有统计学意义(P<0.05);UDH组中CK5/6均呈阳性表达,ADH、DCIS及IDC组中CK5/6大部分呈阴性表达,UDH组与其他3组比较差异有显著性(P<0.05);p63表达量依次为UDH组>ADH组>DCIS组,IDC组中其无阳性表达,各组间差异均有统计学意义(P均<0.05);UDH、ADH和DCIS组中SMA均呈阳性表达,IDC组中其大部分呈阴性表达,与前3组比较,差异均有统计学意义(P均<0.05)。结论联合检测34βE12、CK5/6、p63、SMA表达,有助于鉴别乳腺增生、不典型增生与原位癌,为临床提供可靠的诊疗依据。     

nm23和p53基因与肺腺癌生物学特性的关系

目的：检测肺腺癌组织中nm23表达和p53基因外显子突变情况,寻找有助于准确预测局部肿瘤进展、分型和预后情况的临床参照指标。方法：应用PCR技术检测31例肺腺癌术后存档蜡块组织中nm23表达及p53基因外显子突变情况,并与肺腺癌的病理及临床指标进行相关性分析。结果：nm23表达及p53基因突变率分别为38．7％（12／31）及48．4％（15／31）。nm23表达和p53基因突变与临床分期相关,P值分别为0．005、0．037。结论：nm23表达和p53基因突变与肺癌临床分期和生存相关,在判断肺腺癌细胞增殖、分化程度、恶性程度及预后转归方面有一定价值,可作为判断肺腺癌预后的参考指标,指导高危患者的进一步治疗。     

Immunocytochemical evaluation of human esophageal neoplasms and preneoplastic lesions for beta-chorionic gonadotropin, placental lactogen, alpha-fetoprotein, carcinoembryonic antigen, and nonspecific cross-reacting antigen

Human esophageal neoplasms were studied in comparison to normal, uninvolved, and preneoplastic human esophageal epithelium for the presence of human chorionic gonadotropin (HCG), human placental lactogen (HPL), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and nonspecific cross-reacting antigen (NCA) using the unlabeled antibody peroxidase-antiperoxidase technique. HCG immunoreactivity was identified in 10 of 33 squamous cell carcinomas (33%), in 1 of 6 adenocarcinomas (17%), and 1 of 6 preneoplastic esophageal lesions (17%); while 9 of 33 squamous cell carcinomas (33%) and 1 of 6 adenocarcinomas (17%) contained immunoreactive AFP. Immunoreactive HPL was detected in 6 of 33 squamous cell carcinomas (20%), but in none of the adenocarcinomas. Neither AFP nor HPL immunoreactivity was identified in the 6 hyperplastic lesions which were studied. When stained with an antiserum that was able to detect both CEA and NCA, 27 of 33 squamous cell tumors (82%) and 6 of 6 adenocarcinomas (100%) showed positive immunostaining reactions. Of these, 8 squamous cell carcinomas and 1 adenocarcinoma were subsequently shown to contain only NCA immunoreactivity, while 19 squamous cell carcinomas and 5 adenocarcinomas contained both NCA and CEA immunoreactivity. NCA immunoreactivity alone was identified in 3 of 6 preneoplastic lesions and NCA and CEA immunoreactivity in 1 of 6 preneoplastic lesions. None of the markers was detected in 8 specimens of normal esophageal epithelium which were studied as controls, nor in 6 specimens of uninvolved esophageal epithelium obtained from patients with esophageal cancer. Most tumors expressed 2 or 3 markers, and some tumors were identified which expressed up to 4 of the 5 markers investigated. Only 3 tumors failed to express any of the markers studied. No association was found between the degree of tumor differentiation and presence or absence of HCG immunoreactivity. However, HPL immunoreactivity was more common in poorly differentiated squamous cell carcinomas. In contrast, immunoreactive AFP was more common in well-differentiated squamous cell carcinomas than in other tumor types. Similarly, both CEA and NCA were more frequently expressed in well-differentiated squamous cell carcinomas, adenosquamous carcinomas, and adenocarcinomas than in less differentiated tumors. Our results suggest that HCG, HPL, AFP, CEA, and NCA are tumor-associated antigens in esophageal cancer. Therefore, they could be of value in screening tests for esophageal neoplasms and could be useful in subclassification of esophageal neoplasms.     

Pathological aspects of so called "hilar cholangiocarcinoma"

Cholangiocarcinoma(CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group.However,"hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or,more commonly,the extrahepatic hilar CC.Grossly,a major distinction can be made between papillary and non-papillary tumors.Histologically,most hilar CCs are well to moderately differentiated conventional type(biliary) carcinomas.Immunohistochemically,CK7,CK20,CEA and MUC1 are normally expressed,being MUC2 positive in less than 50% of cases.Two main premalignant lesions are known:biliary intraepithelial neoplasia(BilIN) and intraductal papillary neoplasm of the biliary tract(IPNB).IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma.A series of 29 resected hilar CC from our archives is reviewed.Most(82.8%) were conventional type adenocarcinomas,mostly well to moderately differentiated,although with a broad morphological spectrum;three cases exhibited a poorly differentiated cell component resembling signet ring cells.IPNB was observed in 5(17.2%),four of them with an associated invasive carcinoma.A clear cell type carcinoma,an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.     

Clear cell adenocarcinoma of the uterine cervix in a young pregnant woman: a case report with immunohistochemical study

The patient was a 30-year-old-pregnant woman (para 1, gradiva 1) without in utero exposure to diethylstilbestrol. A papillary and flat lesion was found by colposcopy in the uterine cervix in the routine examination at 10 pregnancy weeks. Biopsies showed papillary and tubular proliferation of malignant cells with clear glycogen-rich cytoplasm and malignant hobnail cells and were diagnosed as clear cell adenocarcinoma. The patient was treated by radical hysterectomy. The lesion of the cervix (10 × 15 × 5 mm) was clear cell adenocarcinoma with mild invasion into shallow myometrium (pTIb). An immunohistochemical study showed that the tumor cells were positive for pancytokeratins (AE1/3, CAM5.2, KL-1, and polyclonal wide), cytokeratin (CK) 7, CK8, CK18, CK19, epithelial membrane antigen, CA 125, p53 protein, and Ki-67 antigen (labeling = 95%). The tumor cells were negative for high-molecular weight CK (34βE12), CK5/6, CK14, CK20, vimentin, AFP, CEA, desmin, S100 protein, α-smooth muscle antigen, CD34, estrogen receptor, progesterone receptor, chromogranin, synaptophysin, neuron-specific enolase, and CD56. The patient is now of free of tumor. In the English literature, the present case is the second case of cervical clear cell adenocarcinoma during pregnancy, and the first case of cervical clear cell carcinoma investigating a wide range of immunoreactive antigens.     

相关蛋白标记物辅助液基薄层细胞检测纤维支气管镜刷片细胞学肺癌分型诊断的探讨

目的 探讨相关蛋白标记物辅助液基薄层细胞检测(TCT)纤维支气管镜刷片细胞学肺癌分型诊断的价值.方法 收集纤维支气管镜刷片细胞学临床诊断剩余标本206例,术后肺肿瘤穿刺标本45例,应用TCT制片技术和免疫细胞化学(ICC)法检测相关蛋白CK10/13、CK7、CK18、CD56和突触素(SYN)在各型肺癌中的表达.结果 CK10/13诊断鳞癌的敏感性和特异性分别为94.7%和72.0%;CK7诊断腺癌的敏感性和特异性分别为98.6%和61.5%;CK18诊断腺癌的敏感性和特异性分别为98.6%和37.5%;CD56诊断小细胞肺癌的敏感性和特异性分别为86.3%和82.9%;SYN诊断小细胞肺癌的敏感性和特异性分别为81.6%和93.5%.CK10/13、CK7和CK18在不同分化鳞癌和腺癌中的表达差异均无统计学意义(均P＞0.05).细胞形态学与ICC联合诊断细胞学未分类癌44例,其中鳞癌、腺癌和小细胞肺癌的分型诊断率分别为90.0%、96.3%和100.O%.结论 相关蛋白ICC检测与细胞学相结合,可提高肺癌分型诊断的准确性,可能成为TCT纤维支气管镜刷片细胞学肺癌分型诊断的一种辅助手段.     

RON及其变异体在肺癌中的表达

目的研究RON及其变异体在肺腺癌中的表达及意义。方法应用免疫组化方法检测106例肺腺癌及35例肺鳞癌中RON的表达情况,并结合临床资料进行统计学分析;通过Western-Blot技术检测31例新鲜肺腺癌组织及9例肺鳞癌组织中RON及其变异体的表达情况,并对RON在不同组织学分级和不同组织学类型中的表达进行统计学分析。结果RON在肺腺癌及鳞癌中都有不同程度的表达,两组比较RON的表达差异具有统计学意义（P〈0.05）;不同分化程度的肺腺癌比较,RON的表达也有差异,低分化的肺腺癌明显高于中分化的腺癌和高分化的腺癌（P〈0.05）;Western-Blot结果显示在肺腺癌和肺鳞癌中均有RON表达;在肺腺癌中观察到RON的变异体,而肺鳞癌中则没有。结论肺癌组织中有RON的过表达,并且肺腺癌中RON的表达明显高于鳞癌（P〈0.05）。肺腺癌中RON的表达与肿瘤分级相关,并存在变异体,而鳞癌则无变异体的表达。     

Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions

Carcinoembryonic antigen (CEA), carbohydrate antigens 15-3, 19-9 and 72-4 (CA 15-3, CA 19-9 and CA 72-4), cytokeratin 19 fragments (CYFRA 21-1), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) were evaluated in pleural fluid for the diagnosis of malignant effusions. With a specificity of 99%, determined in a series of 121 benign effusions, the best individual diagnostic sensitivities in the whole series of 215 malignant effusions or in the subgroup of adenocarcinomas were observed with CEA, CA 15-3 and CA 72-4. As expected, a high sensitivity was obtained with SCC in squamous cell carcinomas and with NSE in small-cell lung carcinomas. CYFRA and/or CA 15-3 were frequently increased in mesotheliomas. Discriminant analysis showed that the optimal combination for diagnosis of non-lymphomatous malignant effusions was CEA + CA 15-3 + CYFRA + NSE: sensitivity of 94.4% with an overall specificity of 95%. In malignant effusions with a negative cytology, 83.9% were diagnosed using this association. The association CYFRA + NSE + SCC was able to discriminate adenocarcinomas from small-cell lung cancers. Regarding their sensitivity and their complementarity, CEA, CA 15-3, CYFRA 21-1, NSE and SCC appear to be very useful to improve the diagnosis of malignant pleural effusions.     

Clinicopathologic characteristics of adenosquamous carcinoma of the lung

Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants.     

Immunohistochemical profile and treatment of uncommon types of thyroid carcinomas

The distinction of uncommon types of thyroid carcinomas is important, because their treatment and prognosis differ. The aim of this study was to describe retrospectively the immunohistochemical profile of uncommon types of thyroid carcinomas and mode of treatment. Of the 1194 patients with thyroid carcinomas treated in Rabin Medical Center from 1954 to 2001, 153 were uncommon types (not papillary or follicular carcinomas). Specimens from archival tissue obtained from thyroidectomies in all these cases were revised and immunohistochemically examined. Anaplastic carcinomas (n=59) were positive for high molecular weight cytokeratin (CK HMW), low molecular molecular weight cytokeratin (CK LMW), cytokeratin (CK) 7, CK 8 and 18, thymoglobulin, EMA and vimentin; medullary carcinomas (n=39) were positive for CK LMW, CK 19, CK 8 and 18, CK 10, CK 7, carcinoembryonic antigen (CEA) and calcitonin; Hurthle cell carcinomas (n=30) for CK LMW, CK 19, CK 8 and 18, thyroglobulin, epithelial membrane antigen (EMA) and CEA; squamous cell carcinomas (SCC) (n=12) for CK HMW and cytokeratin total (CKs); lymphomas (n=7) for leukocyte common antigen (LCA) and B-cells (CD 20), and clear cell carcinomas (n=6) for CK LMW, CEA and thyroglobulin. Use of an immunohistochemical panel has diagnostic value in the differentiation of uncommon types of thyroid carcinoma, which help to plan the best mode of treatment.     

Stainability of lung cancer cells with Leu-7 and OKT-9 monoclonal antibodies

One hundred and one cases of lung cancer were immunohistochemically studied for stainability with Leu-7 (anti-myelin fiber associated glycoprotein) and OKT-9 (anti-transferrin receptor) monoclonal antibodies. All small cell carcinomas and carcinoid tumors were positively stained by Leu-7, and 22 of 41 differentiated adenocarcinomas were also positively stained, especially well-differentiated Clara cell-type adenocarcinoma, (11/14 cases). However, only one of 26 squamous cell carcinomas, one of six large cell carcinomas, one of six adenosquamous carcinomas and none of 16 poorly differentiated adenocarcinomas were stained by Leu-7. On the other hand, all squamous cell carcinomas (26/26 cases), 10 of the 16 poorly differentiated adenocarcinomas, four of the six large cell carcinomas showed positive membranous staining with OKT-9. However, only one of 41 differentiated adenocarcinomas and no small cell carcinomas nor carcinoid tumors were stained by OKT-9. The stainability of lung cancer by these antibodies is discussed.