联合检测TTF1、CK5/6、p63和napsinA在肺鳞癌和腺癌鉴别诊断中的价值

目的 探讨TTF1、CK5/6、p63和napsinA联合检测在肺鳞状细胞癌和腺癌鉴别诊断中的价值.方法 应用免疫组化EnVision法分别检测30例肺鳞状细胞癌和30例肺腺癌中TTF1、CK5/6、p63和napsinA的表达.结果 CK5/6、p63、TTF1和napsinA在肺鳞状细胞癌中的阳性率分别为96.7%、100%、20%和0,同时在肺腺癌中的阳性率分别为10%、20%、86.7%和90%.单个标志物中,CK5/6阳性和napsinA阴性对肺鳞状细胞癌与腺癌的鉴别诊断具有较高的特异性和敏感性;联合标志物检测中,p63和CK5/6共同表达阳性与TTF1和napsinA共同表达阴性在肺鳞状细胞癌的诊断中具有较高的特异性.结论 TTF1、CK5/6、p63和napsinA联合检测可鉴别肺鳞状细胞癌和腺癌,p63和CK5/6共同阳性表达与TTF1和napsinA共同阴性表达更加支持肺鳞状细胞癌,而非肺腺癌,反之亦然.     

TTF-1、SP-A在肺腺癌诊断及鉴别诊断中的价值

目的 评价甲状腺转录因子-1(TTF-1)、肺泡表面活性蛋白A (SP-A)在肺腺癌中表达的敏感性和特异性,探讨他们在肺腺癌诊断及鉴别诊断中的价值.方法 选择经组织学和临床资料证实的肺原发性腺癌40例、转移性腺癌13例,采用免疫组化EnVision法检测TTF-1及SP-A的表达情况.结果 40例肺腺癌中有32例表达TTF-1、27例表达SP-A;13例转移性腺癌中只有1例肝细胞癌胞质表达TTF-1、无SP-A表达.TTF-1和SP-A在肺腺癌中表达的敏感性分别为80%和67.5%、特异性均为100%.结论TTF-1在肺腺癌中表达有较高的敏感性和特异性,在排除甲状腺癌可能后,可作为鉴别肺原发性和转移性腺癌的可靠标记;而SP-A敏感性较低且随分化程度降低表达下降,故TTF-1对肺腺癌鉴别诊断的价值优于SP-A.     

一组细胞角蛋白抗体在胸腹腔积液中的表达及其鉴别诊断价值

目的:探讨一组细胞角蛋白抗体在胸腹腔积液中的表达情况及其临床应用价值。方法:选取72例胸腹腔积液标本,其中腺癌30例,鳞癌22例,反应增生性间皮细胞22例,应用细胞免疫化学SP法检测细胞角蛋白CK(AE1/AE3)、细胞角蛋白5/6(CK5/6)、细胞角蛋白18(CK18)的表达。结果:三种抗体在反应增生性间皮细胞、腺癌细胞、鳞癌细胞中阳性率分别是CK(AE1/AK3):10.0%,73.3%,68.2%;CK5/6:60.0%,6.7%,77.3%;CK18:0,80.0%,4.5%。组合CK(AE1/AE3)(-)、CK5/6(+)、CK18(-)检测间皮细胞的敏感性为93.3%,特异性为80.2%;CK5/6(-)、CK18(+)检测腺癌细胞的敏感性为84.7%,特异性为93.6%;CK(AE1/AE3)(+)、CK5/6(+)、CK18(一)检测鳞癌细胞的敏感性为86.4%,特异性为92.8%。结论:多项细胞角蛋白联检提高了诊断反应增生性间皮细胞、腺癌细胞、鳞癌细胞的敏感性和特异性,可辅助细胞形态学对于良恶性胸腹腔积液的鉴别诊断。     

恶性上皮性肿瘤中CK20的表达及其临床意义

目的　研究单克隆抗体CK2 0在恶性上皮性肿瘤和卵巢转移性腺癌组织中的表达及其意义。方法　应用S P法对鼻咽非角化性癌、乳腺浸润性导管癌、肺的鳞癌和腺癌、卵巢黏液性囊腺癌、胃腺癌和结肠直肠腺癌各组总计 6 7例和 4 1例分别进行了CK2 0和CK19检测。结果　CK2 0阳性率 :肺腺癌 1/ 7(14 3% ) ,卵巢浆液性和黏液性腺癌 3/ 12 (33 3% ) ,胃腺癌 3/ 9(33 3% ) ,结肠直肠腺癌组 2 1/ 2 2 (95 5 % ) ,其他癌组织均呈阴性。结肠直肠腺癌组组与其他各组间比较差异有显著性 (P <0 0 1)。CK19在上述 4 1例癌组织中均呈强阳性表达。结论　CK2 0表达对鉴别结肠腺癌和直肠腺癌与肺腺癌和乳腺浸润性导管癌具有高度特异性和较高的敏感性 ;CK2 0高表达对鉴别卵巢原发性腺癌与卵巢的结肠腺癌或直肠腺癌转移具有一定的意义     

109例支气管活检肺腺癌的临床病理分析

目的观察肺腺癌的临床病理特征、诊断及鉴别诊断。方法对109例肺腺癌患者的临床及病理资料进行回顾性分析,并根据2011年肺腺癌新分类对109例肺腺癌标本重新进行镜下观察和免疫组化评估。结果肺腺癌临床主要症状为咳嗽、气短及胸痛,CT扫描常表现为实性的结节、毛玻璃样斑块和实性/毛玻璃样斑块。肺腺癌主要组织学类型包括:浸润前病变、微浸润性病变、浸润性病变。免疫表型:肺腺癌组织中CK7阳性率为100%,TTF1阳性率为72.2%,未见CK5/6表达。结论肺腺癌的诊断及鉴别诊断主要依靠临床资料、组织学特征及免疫表型。     

特异性抗体在乳腺癌和肺腺癌鉴别诊断中的应用及异常表达率的研究

目的探讨GATA3、ER、PR、TTF-1、Napsin A在乳腺癌及肺腺癌中的敏感性、特异性、异常表达率及其组合在鉴别诊断中的应用价值。方法采用免疫组化法检测GATA3、ER、PR、TTF-1、Napsin A在152例乳腺癌及116例浸润性肺腺癌中的表达,阳性细胞所占比率≥10%定义为阳性。用MedCalc软件统计各抗体及组合抗体在乳腺癌及肺腺癌鉴别诊断中的敏感性及特异性。结果 GATA3表达于87.5%的乳腺癌(管腔A/B型100%、HER-2阳性型79.2%、三阴型39.1%)及3.4%的肺腺癌(非黏液腺癌2.7%,黏液腺癌16.7%,P=0.194)。GATA3在ER阳性及阴性乳腺癌中的阳性率差异有显著性(100%vs59.6%,P0.05)。TTF-1表达于96.5%的肺腺癌(非黏液腺癌98.2%,黏液腺癌66.7%,P=0.013)及1.3%的乳腺癌(管腔A/B型0.9%、HER-2阳性型0、三阴型4.3%)。Napsin A表达于87.1%的肺腺癌(非黏液腺癌88.2%,黏液腺癌66.7%,P=0.172),乳腺癌均未见表达。肺腺癌表达ER(10.2%)、PR(1.7%)。GATA3对乳腺癌的敏感性及特异性均优于ER(87.50%vs 69.08%,96.55%vs 89.66%),而TTF-1对肺腺癌的敏感性优于Napsin A(96.55%vs 85.34%)。GATA3/TTF-1组合可鉴别87.5%的乳腺癌及93.1%的肺腺癌,而TTF-1/GATA3均阳性见于3.4%的肺腺癌及1.3%的乳腺癌。结论少数肺腺癌及乳腺癌可异常表达GATA3及TTF-1,特别是在三阴型乳腺癌及肺黏液腺癌中异常表达率偏高。在穿刺活检标本任何一种抗体都不能单独作为鉴别两者的依据。GATA3/TTF-1标记是鉴别乳腺癌及肺腺癌的首选抗体,而ER、PR及Napsin A对于鉴别诊断有较好的辅助作用。     

一种较p63特异性更高的鉴别非典型纤维黄色瘤和其他皮肤恶性梭形细胞肿瘤的标志物--p40

非典型纤维黄色瘤( AFX)是一种生长迅速的皮肤肿瘤,常累及老年人受日光照射的头颈部皮肤。典型的AFX由增生的恶性梭形和上皮样细胞构成膨胀性或浸润性的结节状结构,位于紧靠表皮的真皮层中,累及皮下组织罕见,瘤细胞怪异,多形性显著,核分裂丰富。鉴别诊断包括低分化梭形细胞鳞癌( SpSCC)、梭形细胞黑色素瘤、平滑肌肉瘤和血管肉瘤等。目前对于 AFX的组织发生及鉴别诊断仍存在争议,该病是一种排除性诊断(需广谱CK、S-100、肌源性标志物和血管标志物均阴性),若误诊造成的后果将非常严重。AFX罕有复发或转移,属惰性生物学行为,外科切除即可,而其他需要鉴别的恶性梭形细胞肿瘤的复发/转移率高于AFX。其他病变通过S-100、desmin、CD31等免疫标记较易鉴别,在少见情况下SpSCC中CK可阴性,且p63的阳性率最高只有83%,特异性不足,在AFX中可有9%的阳性率。近年来,有关食管、头颈部、肺等部位的鳞状细胞癌的研究显示p40较p63有更高的特异性,因此作者采用免疫组化法观察104例皮肤恶性肿瘤(包括中分化鳞状细胞癌27例、SpSCC 26例、AFX 27例、梭形细胞黑色素瘤24例)中p40的表达,并比较p40与p63在鉴别AFX和SpSCC的准确性差异,结果显示 p40与 p63在中分化鳞状细胞癌中的阳性率均为100%,在 SpSCC 中的阳性率分别为96.1%和92.3%,在AFX中的阴性率分别为100%和70.4%,在梭形细胞黑色素瘤中二者均有少数病例呈局灶弱阳性表达。统计学分析显示：p40和p63在诊断皮肤SpSCC方面具有相同的敏感性,但p40的特异性高于p63(P=0.01),其阳性染色更支持Sp-SCC,而非AFX。     

CK7、CK20联合肠道源性标志物检测在肺肠型腺癌和转移性结直肠腺癌鉴别诊断中的价值

目的检测肺肠型腺癌(pulmonary enteric adenocarcinoma,PEAC)和肺转移性结直肠腺癌(pulmonary metastatic colorectal adenocarcinoma,PMCA)中CK7、CK20和肠道源性标志物(CDX2、SATB2、CDH17、β-catenin)的表达,探讨其在两者鉴别诊断中的价值。方法应用免疫组化EnVision法检测11例PEAC和22例PMCA中CK7、CK20、CDX2、SATB2、CDH17和β-catenin的表达,分析其在两者鉴别诊断中的敏感性、特异性、阳性预测值和阴性预测值。结果CK7在PEAC中的表达高于PMCA,CK20、CDX2、SATB2、CDH17和β-catenin在PMCA中的表达均明显高于PEAC,差异有统计学意义(P<0.05)。SATB2和β-catenin的表达对PEAC与PMCA的鉴别诊断,具有较高的特异性和阳性预测值(100%)。CK7^-/CK20^+联合肠道源性标志物对PEAC和PMCA的鉴别诊断,均有较高的特异性和阳性预测值(100%)。结论SATB2或β-catenin是鉴别PEAC与PMCA高度特异性的免疫组化标志物,联合CK7和CK20可以提高PEAC病理诊断的准确性。     

p53、p21~(WAF1)蛋白在非小细胞肺癌中的表达及其临床意义

目的　探讨原发性非小细胞肺癌中p5 3、p2 1WAF1蛋白表达与临床病理及预后的关系。方法　应用免疫组织化学 (SP法 )方法。共检测非小细胞肺癌 147例 ,其中腺癌 6 6例 ,鳞癌 6 3例 ,腺鳞癌 14例 ,大细胞癌 4例。结果　p5 3蛋白总阳性率为 6 1.2 % (90 / 147) ,腺癌为 5 7.6 % (38/ 6 6 ) ,鳞癌阳性率为 6 3.5 % (4 0 / 6 3) ,腺鳞癌为 71.4% (10 / 14) ,大细胞癌 2例阳性。p2 1WAF1蛋白总阳性率为40 1% (5 9/ 147) ,腺癌为 42 .4% (2 8/ 6 6 ) ,鳞癌为 41.3% (2 6 / 6 3) ,腺鳞癌 2 8.6 % (4 / 14) ,大细胞癌 1例阳性。肺腺癌p5 3蛋白阳性表达与其预后相关 ,6 6例腺癌中 ,生存率低于 3年组和高于 3年组的p5 3蛋白阳性率分别为 75 % (2 1/ 2 8)和 44 .7% (17/ 38) ,差异有显著性意义 (P <0 .0 2 5 )。p2 1WAF1阳性表达与肺癌预后有关 ,p2 1WAF1阳性表达者 3年生存率 (6 4.4% )高于阴性表达者 (4 6 .6 % ) (P <0 .0 5 )。p5 3阳性而p2 1WAF1阴性的非小细胞肺癌患者的预后比p5 3阴性而p2 1WAF1阳性者差 (P <0 .0 1)。结论　检测p5 3蛋白表达可作为判断肺腺癌预后的指标之一 ;检测p2 1WAF1蛋白表达有利于对非小细胞肺癌预后的判断 ;联合检测p5 3、p2 1WAF1蛋白对判断非小细胞肺癌的预后有重要的意义 ,似可作     

伴皮脂腺分化的腺样囊性癌和鳞癌构成的食管碰撞瘤1例并文献复习

目的探讨伴皮脂腺分化的腺样囊性癌和鳞癌构成的食管碰撞瘤的临床病理学特征、诊断及鉴别诊断。方法回顾性分析1例伴皮脂腺分化的腺样囊性癌和鳞癌构成的发生在食管的碰撞瘤,分析其临床表现、组织病理学特征和免疫表型,并复习相关文献。结果胃镜下见距门齿34～37cm处食管见一隆起型灰黄色肿物,组织学表现为双原发肿瘤,糜烂区为中分化鳞癌,浸润黏膜下层,周围可见鳞状上皮不典型增生;隆起型灰黄色肿物主要由3种不同组织构型区域融合构成。免疫表型:未分化基底样细胞CK8/18、CAM5. 2、p63、p40、GATA-3、S-100均(+),CK5/6、CK7均灶(+),AR、GCDFP-15、SMA均(-);腺样囊性癌样区域:腺上皮CK8/18、CAM5. 2、CK7均(+),基底细胞p63、p40、CK5/6、S-100、CD117均(+),SMA、AR、GCDFP-15、GATA-3均(-);皮脂腺分化区域:CK5/6、p40、GATA-3、EMA均(+),SMA灶(+); AR、GCDFP-15、vimentin、CD117、CD15均(-);鳞癌区域:p40、p63、CK5/6均(+)。随访56个月,患者无复发及转移。结论伴皮脂腺分化的腺样囊性癌和鳞癌构成的食管碰撞瘤临床罕见,需与基底细胞样鳞癌、黏液表皮样癌、腺鳞癌及MuiR-Torre综合征鉴别。     

Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas

In this study, we sought to validate the importance of p63, CK5/CK6, CK7, and surfactant-A (SP-A) to classify 42 non-small cell lung cancers in autopsy and surgical resection specimens and to study the usefulness of these markers in distinguishing between squamous cell carcinomas and adenocarcinomas because of their different implications regarding treatment and prognosis. All adenocarcinoma cases were negative for p63; 9 (56.2%) of 16 were CK5/CK6 positive, 16 (94.1%) of 17 were CK7 positive, and 4 (26.6%) of 15 were SP-A positive. In squamous cell carcinoma, 1 case was CK7 and SP-A positive and 14 (77.8%) of 18 were p63 positive. The latter appears to be useful in differentiating squamous cell carcinoma from adenocarcinoma of the lung in small biopsies without keratinization or glandular differentiation; thus, for advanced-stage cases, where there is no possibility of surgical resection and the treatment of choice is radiotherapy plus chemotherapy, we would be able to differentiate between the two histological types, establishing then a different therapy.     

Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from adenocarcinoma in lung fine‐needle aspiration specimens

The current FDA‐approved standard of care for nonsmall cell lung cancer is Carboplastin/Taxol/Avastin based upon an impressive survival benefit; however, patients with squamous carcinoma (SQCC) cannot receive Avastin because of a 30% mortality rate due to fatal hemoptysis. In this study we evaluated the role of cytomorphology and immunohistochemistry in differentiating SQCC from adenocarcinoma (ADC) in lung FNA specimens. The case cohort included 53 FNA cases of nonsmall cell lung carcinoma with surgical pathology follow‐up. All FNA specimens were reviewed independently by a panel of cytopathologists to differentiate between SQCC and ADC. The cell block material was available in 23 cases (11 ADC and 12 SQCC) to perform immunohistochemical stains for TTF‐1, CK7, CK20, P63, and CK5/6. On surgical resection, 35/53 (66%) cases were diagnosed as ADC and 18/53 (34%) as SQCC. The number of cases classified correctly on the basis of cytomorphology was 66% for ADC and 53% for SQCC (combined accuracy 60%). By immunohistochemical staining, 14/23 (61%) cases expressed TTF‐1. Nine cases were TTF‐1 negative; eight of the TTF‐1 negative cases (89%) were SQCC. Twenty‐three cases expressed CK7 (87%); one ADC case (4%) showed focal CK20 positivity. Both P63 and CK5/6 expression was seen in 9/12 (75%) SQCC cases; none of the ADC cases showed this dual expression. Cytomorphology alone may not be able to stratify all cases of nonsmall cell lung carcinoma into ADC and SQCC in FNA specimens. The immune‐panel of TTF‐1, CK7, CK20, P63, and CK5/6 is useful in differentiating SQCC from ADC. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma

Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes ΔNp63-a p63 isoform suggested to be highly specific for squamous/basal cells. Here we compared the standard p63 antibody (4A4) and p40 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas (n=81), adenocarcinomas (n=237), and large cell lymphomas (n=152). The p63 was positive in 100% of squamous cell carcinomas, 31% of adenocarcinomas, and 54% of large cell lymphomas (sensitivity 100%, specificity 60%). In contrast, although p40 was also positive in 100% of squamous cell carcinomas, only 3% of adenocarcinomas, and none of large cell lymphomas had p40 labeling (sensitivity 100%, specificity 98%). The mean percentage of p63 versus p40-immunoreactive cells in squamous cell carcinomas was equivalent (97 vs 96%, respectively, P=0.73). Rare adenocarcinomas with p40 labeling had reactivity in no more than 5% of tumor cells, whereas the mean (range) of p63-positive cells in adenocarcinomas and lymphomas was 26% (1-90%) and 48% (2-100%), respectively. In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity, which eliminates a potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as squamous cell carcinoma. These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma.     

Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas.

To facilitate the differential diagnosis of poorly differentiated metastatic carcinomas of unknown primary site, we evaluated p63 and cytokeratin (CK) 5/6 as immunohistochemical markers for squamous cell carcinomas. The study cases were as follows: squamous cell carcinoma of the lungs, head/neck, esophagus, cervix uteri, or anal canal, 73; non-squamous cell carcinomas of various primary sites, 141; and urothelial carcinoma, 20. We also tested 14 malignant mesotheliomas. Immunoreactivity for p63 was as follows: squamous cell carcinomas, 59 (81%); urothelial carcinoma, 14 (70%), most often with diffuse staining patterns; non-squamous cell carcinomas, 20 (14.2%), resulting in a specificity of 0.86 of p63 for squamous cell carcinomas. Coexpression of p63 and CK5/6 had a sensitivity of 0.77 and a specificity of 0.96 for squamous cell carcinomas. Increasing the minimal criterion of positive immunostaining for both markers to more than 50% of immunoreactive tumor cells resulted in a specificity of 0.99, although the sensitivity diminished to 0.66. All malignant mesotheliomas were negative for p63. Our data suggest that positive immunostaining for both p63 and CK5/6 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin.     

Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma

For treatment purposes, distinction between squamous cell carcinoma and adenocarcinoma is important. The aim of this study is to examine the diagnostic accuracy on lung cancer small biopsies for the distinction between adenocarcinoma and squamous cell carcinoma and relate these to immunohistochemical and KRAS and EGFR mutation analysis. An interobserver study was performed on 110 prospectively collected biopsies obtained by bronchoscopy or transthoracic needle biopsy of patients with non-small cell lung cancer. The diagnosis was correlated with immunohistochemical (IHC) analysis for markers of adeno- (TTF1 and/or mucin positivity) and squamous cell differentiation (P63 and CK5/6) as well as KRAS and EGFR mutation analysis. Eleven observers independently read H&E-stained slides of 110 cases, resulting in a kappa value of 0.55?±?0.10. The diagnosis non-small cell lung cancer not otherwise specified was given on average on 29.5?% of the biopsies. A high concordance was observed between hematoxylin?Ceosin-based consensus diagnosis (??8/11 readings concordant) and IHC markers. In all cases with EGFR (n?=?1) and KRAS (n?=?20) mutations, adenodifferentiation as determined by IHC was present and p63 staining was absent. In 2 of 25 cases with a consensus diagnosis of squamous cell carcinoma, additional stainings favored adenodifferentation, and a KRAS mutation was present. P63 is most useful for distinction between EGFR/KRAS mutation positive and negative patients. In the diagnostic work-up of non-small cell lung carcinoma the limited reproducibility on small biopsies is optimized with immunohistochemical analysis, resulting in reliable delineation for predictive analysis.