单/双酶标记鸡尾酒抗体AMACR/p63/34βE12在前列腺穿刺组织鉴别诊断中的对比观察

前列腺穿刺标本良恶性鉴别诊断是临床病理诊断工作的难点之一。近年来通过应用α-甲酰基辅酶A消旋酶（AMACR）、34βE12、p63抗体分别检测前列腺癌细胞和基底细胞，提高前列腺癌诊断的准确性已得到普遍认同。Jiang等在2005年首先使用混合型AMACR／p63／34βE12抗体和双酶标记法检测前列腺癌，国内也有单酶标记鸡尾酒抗体AMACR／p63／34βE12检测前列腺癌的报道，但单酶标记与双酶标记鸡尾酒抗体两种试剂染色的比较研究尚未见报道。我们采用单酶标记的鸡尾酒抗体和双酶标记的混合型抗体标记前列腺穿刺标本，以评价两种方法在前列腺癌的鉴别诊断中的应用价值。[第一段]     

单/双酶标记鸡尾酒抗体AMACR/p63/34βE12在前列腺穿刺组织鉴别诊断中的对比观察

前列腺穿刺标本良恶性鉴别诊断是临床病理诊断工作的难点之一.近年来通过应用α-甲酰基辅酶A消旋酶(AMACR)、34βE12、p63抗体分别检测前列腺癌细胞和基底细胞,提高前列腺癌诊断的准确性已得到普遍认同[1～5].Jiang等[6]在2005年首先使用混合型AMACR/p63/34βE12抗体和双酶标记法检测前列腺癌,国内也有单酶标记鸡尾酒抗体AMACR/p63/34βE12检测前列腺癌的报道[7,8],但单酶标记与双酶标记鸡尾酒抗体两种试剂染色的比较研究尚未见报道.我们采用单酶标记的鸡尾酒抗体和双酶标记的混合型抗体标记前列腺穿刺标本,以评价两种方法在前列腺癌的鉴别诊断中的应用价值.     

抗体鸡尾酒AMACR/P63/34βE12在前列腺良恶性病变鉴别诊断中的应用价值

目的:探讨抗体鸡尾酒AMACR/P63/34βE12在前列腺良恶性病变鉴别诊断中的应用价值。方法:收集2001~2005年111例前列腺手术切除标本，其中前列腺腺癌39例，高级别前列腺上皮内瘤（high-grade prostatic intraepithelial neoplasias，HGPIN）29例，非典型性腺瘤样增生（atypical adenomatous hyperplasia, AAH）3例，前列腺结节性增生（benign prostatic hyperplasia, BPH）40例。作抗体鸡尾酒AMACR/P63/34βE12的免疫标记，观察3种抗体在各类病变中的表达情况。结果:39例前列腺腺癌AMACR全部呈阳性，癌巢周围无基底细胞残存（P63/34βE12阴性）。29例高级别前列腺上皮内瘤变，14例（48.3%）腺泡上皮AMACR呈阳性，29例腺泡上皮周围有连续或不连续的基底细胞（P63/34βE12阳性）。3例非典型性腺瘤样增生中2例腺泡上皮AMACR呈弱阳性；3例腺泡上皮周围有较连续的基底细胞（P63/34βE12中度阳性）。40例前列腺结节性增生，腺泡上皮AMACR染色均呈阴性，周围有连续的基底细胞（P63/34βE12强阳性）。结论:鸡尾酒抗体AMACR/P63/34βE12标记前列腺组织，能够同时高特异性和敏感性地检测出前列腺腺癌细胞（或非典型增生的腺泡上皮细胞）和基底细胞，为前列腺腺癌与高级别上皮內瘤变、非典型性腺瘤样增生、前列腺结节性增生的鉴别诊断提供有力的证据。     

高分子量角蛋白抗体(34βE12)在前列腺癌诊断中的应用价值

目的：研究高分子量角蛋白抗体（３４βＥ１２）在前列腺癌诊断中的作用。方法：采用微波ＥｎＶｉｓｉｏｎ免疫组织化学方法,观察３４βＥ１２抗体在不同前列腺病变中的染色情况。结果：基底细胞特异性细胞角蛋白抗体３４βＥ１２与所有的前列腺良性病变的基底细胞胞浆特异性染色。１５例前列腺癌中１２例３４βＥ１２染色为阴性,有３例出现阳性反应。原发性前列腺导管癌的癌巢外周有连续或不连续的基底细胞围绕。结论：３４βＥ１２染色阳性不是诊断良性前列腺病变的绝对指标。前列腺癌的诊断必须综合考虑临床、常规组织学检查及免疫组织化学结果才能做出正确的诊断。     

混合型p504s/34βE12/p63抗体在前列腺腺癌诊断中的应用价值

目的评价混合型p504s/34βE12/p63抗体和双重染色技术在诊断前列腺腺癌中的价值。方法选择47例前列腺病例,包括36例前列腺癌、4例不典型腺瘤样增生、4例良性增生和3例间质肉芽肿性炎。采用混合型p504s/34βE12/p63抗体和双酶标记法检测这3种抗原在各类病变中的表达状况。p504s阳性表现为胞质内蓝黑色颗粒状物,而基底细胞的核(p63)和胞质(34βE12)呈红色着色。结果在36例前列腺癌中,32例(88·89%)表达p504s,其中5例为小灶性癌,所有癌细胞巢周围无肌上皮细胞(34βE12和p63阴性)。在4例不典型腺瘤样增生中,1例p504s阳性,但腺上皮细胞周围也有肌上皮细胞(34βE12和p63阳性)。其余7例良性病变中p504s阴性。无非癌性病变同时出现p504s阳性而34βE12和p63阴性的情况。单标抗体p504s和混合型p504s在前列腺病变中的表达一致率为91·49%。结论混合型p504s/34βE12/p63抗体双标在前列腺癌的诊断中具有很高的敏感性和特异性,与单标抗体比较,更容易观察、分辨,有助于提高小灶性前列腺癌的检出率。该法适用于常规病理诊断中,尤其是穿刺活检的小标本,而且减少了免疫组化染色片的数量。     

抗体鸡尾酒p504s/p63标记在前列腺癌诊断中的应用

随着前列腺癌发病率的增高,对前列腺癌的诊断,特别是对高分化肿瘤的判断,显得越来越重要。为辅助形态病理诊断,我们将抗体鸡尾酒p504s/p63标记应用于前列腺癌标本的鉴别诊断上,增加了结果判断的准确性。材料与方法.1材料前列腺切除及针吸活检组织,经15%缓冲福尔马林固定,石蜡包     

前列腺活检诊断中p504s与34βE12的应用

在前列腺活检中,经常会碰到组织学类似于前列腺癌(PA)的病变,有时靠HE切片难以诊断。PA的标记物p504s具有较佳的特异性和敏感性,尤其是与34βE12联合标记,对鉴别前列腺良恶性病变有很大帮助。1材料与方法1.1材料收集宁波市鄞州人民医院2000年1月~2004年12月前列腺活检标本759例     

P504S、34βE12双重免疫组织化学染色在前列腺癌诊断中的应用

前列腺癌是老年男性常见的恶性肿瘤之一。近年来发病率逐渐上升。随着微创技术的发展,穿刺组织中微小癌的诊断越来越多,美国近期发现的前列腺癌的平均直径在1cm左右。前列腺癌的诊断主要依赖于光镜病理检查,但高分化前列腺癌和前列腺上皮内肿瘤（PIN）的差别非常小,有时单凭HE染色难以鉴别,     

高分子量角蛋白抗体（34βE12）在前列腺癌诊断 …

目的：研究高分子量角蛋白抗体（３４βＥ１２）的前列腺癌诊断中的作用。方法：采用微波ＥｎＶｉｓｉｏｎ免疫组织化学观察３４βＥ１２缺本在不同前列腺病变中的染色情况。结果：基底细胞特异性细胞角蛋白抗体３４βＥ１２与所有的前列腺良性病变的基底细胞胞浆特异性染我。１５例前列腺癌中１２例３４βＥ１２染色为阴性，有３例出现阳性反应，原发性前列腺导管癌的癌巢外周有连续或不连续的基底细胞围绕。结论：３４βＥ１２染色     

Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.     

Alpha-methylacyl-CoA racemase (P504S)/34betaE12/p63 triple cocktail stain in prostatic adenocarcinoma after hormonal therapy

Alpha-methylacyl-CoA racemase (AMACR) has recently been shown to be a highly sensitive marker for the diagnosis of prostate cancer. However, there is limited information concerning its utility as a marker for prostate carcinoma after hormonal therapy. Our current investigation was conducted to evaluate the expression of AMACR in patients with prostate carcinoma after hormonal therapy and assess its diagnostic utility in combination with p63 and high molecular weight cytokeratin (34betaE12) staining. Prostate tissues from 49 patients who had been treated with hormonal therapy were immunohistochemically analyzed for AMACR, 34betaE12, and p63 expression by a triple antibody cocktail stain. The staining intensities and the percentages of positively staining tumor cells were recorded. The correlations between AMACR expression and metastatic status, associated hormonal therapy regimens, and the extent of hormone therapy effect were analyzed. All malignant acini were completely negative for both basal cell markers (34betaE12 and p63). Tumor cells failed to demonstrate expression of AMACR in 14 (29%) of 49 cases. In the remaining 35 cases (71%), positive immunostaining for AMACR was noted, but with variable intensities and percentages of cells stained. Positive staining for AMACR in benign glands was not seen in any case. In all cases, basal cells were strongly stained by p63 in benign acini with a mean positive percentage of 96%. Similarly, basal cells in benign acini displayed moderate staining intensities for 34betaE12 in 3 (7%) of 41 cases and strong immunostaining for this marker in the remaining 38 cases (93%); the mean percentage of positive cells was 92%. alpha-methylacyl-CoA racemase expression may be substantially diminished or entirely lost in prostate carcinoma after hormonal therapy. This variation in AMACR expression does not correlate with the metastatic status, the modality of hormonal therapy, or the extent of therapy-related effect. It is important that pathologists be aware that some hormonally treated prostate carcinomas do not express AMACR, and that immunostaining in such cases must be interpreted with caution. A triple cocktail stain using AMACR, 34betaE12, and p63 can be helpful in evaluating prostate specimens for the presence of residual or recurrent carcinoma after hormonal therapy for cancer.     

Usefulness of basal cell cocktail (34betaE12 + p63) in the diagnosis of atypical prostate glandular proliferations

We evaluated the diagnostic usefulness of the 34betaE12-p63 cocktail, compared with 34betaE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3 transurethral resection specimens containing atypical glandular proliferations and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining intensity; percentage of basal cells staining in benign, atypical, and malignant glands; number of benign glands lacking basal cell staining; and staining variance were analyzed. All NBXs with unequivocal PCa were negative with all 3 markers. Diagnoses were as follows for the atypical cases after staining for the 3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign atypical proliferations, 4; and HGPIN with adjacent small atypical acinar proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong staining intensity and improved basal cell staining in morphologically benign and benign atypical glands compared with p63 and 34betaE12 alone; it had the smallest staining variance compared with 34betaE12 (F < 0.0001) and p63 (F = 0.31), although its advantage for resolving individual atypical cases was limited compared with 34betaE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally was resolved as benign using the cocktail and p63. Because the diagnosis of PCa is supported by lack of basal cell staining, the immunohistochemical analysis with highest possible sensitivity and lowest possible variability is critical to ensure that a negative reaction is true. The cocktail provides a simple, cost-effective improvement in basal cell immunohistochemical analysis of difficult prostate lesions.     

细胞角蛋白34βE12在鉴别乳腺良、恶性病变中的意义

目的 探讨高分子量细胞角蛋白34βE12作为良性病变的标记物对鉴别乳腺病变的意义。方法收集90例有随访活检和组织病理学诊断对照的乳腺细针吸取细胞学(FNAC)资料：良性病变50例,包括非增生性病变30例和增生性病变20例、导管内癌10例和浸润癌30例,对其FNAC涂片和相应的石蜡切片作34βE12的抗生物素蛋白-生物素-过氧化酶复合(ABC)法免疫组织化学分析。利用SPSS10．0软件进行统计学分析。结果 (1)34βE12在良性非增生和增生性病变组中的表达差异无显著性。(2)34βE12在良性病变和癌组中的表达差异具显著性,34βE12在癌组中,FNAC涂片和相应的石蜡切片分别为66．7％和63．3％的病例表现为完全阴性或散在1 的肿瘤细胞胞质阳性;在良性病变组中,FNAC涂片和相应的石蜡切片分别为100％和78％的病例表现为2 至3 的细胞阳性,且在石蜡切片中34βE12表现为完整的细胞膜和细胞质的强阳性,与癌中阳性标本之细胞质颗粒状阳性为主的表达特点不同。(3)34βE12在细胞分化较好的筛孔型、乳头型和实性型导管内癌中为完全阴性和散在细胞胞质阳性,而在细胞分化较差的粉刺型导管内癌中为阴性至3 的细胞阳性。结论 34βE12可作为乳腺病变鉴别诊断中良性病变的标记物,上皮细胞出现34βE12表达缺失时高度提示为癌;大量上皮细胞表达34βE12,且为细胞膜强阳性时,则应多考虑为良性病变。     

The significance of atypical adenomatous hyperplasia and prostatic intraepithelial neoplasia for the development of prostate carcinoma

The term prostatic intraepithelial neoplasia (PIN) is an accepted diagnosis in pathology of the prostate. The diagnostic difference between atypical adenomatous hyperplasia (AAH) and adenosis is still under debate. A number of questions remain about the significance of grading of AAH and PIN, the biology of AAH and PIN as precursors of carcinoma, the possibility of treatment of AAH and PIN and whether AAH- and PIN-associated cancers differ from non-associated carcinoma. This paper reviews the results and discussions at the First International Consultation Meeting on Atypical Adenomatous Hyperplasia and Prostatic Intraepithelial Neoplasia and the Origins of the Prostatic Carcinomas. AAH is an architectural atypia of the prostate. The histological and cytological features of AAH are intermediate between BPH and low-grade carcinoma of the prostate. Cell kinetic findings show no distinct neoplastic pattern. AAH may be a precursor of transition zone carcinoma but the findings to date are inconclusive. Follow up studies should address whether the association of AAH and carcinoma is incidental or whether transition occurs between AAH and carcinoma. In contrast, PIN is an accepted preneoplastic lesion and the most likely precursor of the dorso-peripheral zone carcinoma. The diagnosis of high-grade PIN is clinically important, because high-grade PIN is associated with carcinoma in a high percentage of patients (38–100%). AAH- and PIN-associated cancers may not differ from other prostatic cancers. At present treatment for AAH and PIN without carcinoma is not indicated, but high-grade PIN warrants surveillance and follow up of the patient to identify a possible coexisting cancer. It must be stressed that AAH and PIN are multifocal lesions and both are age-associated.Prepared following the First International Consulting Meeting on Prostatic Intraepithelial Neoplasia and the Origins of Prostatic Carcinoma, Ancona, 11–12 September 1994     

前列腺癌及前列腺上皮内瘤6号染色体等位基因杂合子丢失分析

目的：检测原发性前列腺癌及高级别前列腺上皮内瘤（PIN）6号染色体等位基因杂合子丢失（LOH）及其意义。方法：经显微切割技术切获取前列腺癌及PIN各10例患者DNA,采用聚合酶链反应（PCR）及微卫星多态性技术,对6号染色体上的20个微卫星标志位点LOH进行检测。结果：10例原发性前列腺中有8例在6号染色上至少有1个位点检测到LOH,6p21-6q23及6q25-6q27为2个高频LOH区,10例高级别PIN检测6号染色体20个位点,有5例各有1个位点检测到LOH,结论：前列腺癌中存在6号染色体的高频LOH区,分别位于6q21-6q23,6q25-6q27区,编码细胞周期素C及胰岛素样生长因子Ⅱ受体的基因为此2区侯选的抑癌基因,它们可能与前列腺癌的发生发展有关。     

Comparison of 34betaE12 and P63 in 100 consecutive prostate carcinoma diagnosed by needle biopsies.

P63, a homologue of p53, was recently identified as a useful basal cell-specific marker. We compared the sensitivity and specificity of p63 with the widely used high-molecular-weight keratin 34betaE12 for the diagnosis of prostate carcinoma in needle biopsies. We selected 100 consecutive prostate carcinoma diagnosed by needle biopsies with an adequate number of cancerous glands on the slide. We chose 1 representative hematoxylin and eosin-stained slide from each case and gave it a Gleason score. The same paraffin block was retrieved for 34betaE12 and p63 stains. We compared staining patterns of 34betaE12 and p63 on both malignant glands and benign glands and recorded basal cell density (percentage of basal cells with positive staining in the benign glands). The cases were divided into 3 groups according to the Gleason score: 5 to 6 (31 cases), 7 (46 cases), and 8 to 10 (23 cases). In 20 cases, focal and patchy staining in a basal cell distribution in malignant glands (range, 1%-20%; mean, 6.6%) was demonstrated (19 by both stains and 1 by 34betaE12 only). In 1 case with a Gleason score of 9, the cancer cells, not the basal cells, were stained focally by p63 but not by 34betaE12. Higher-grade tumors demonstrated higher numbers of malignant glands with basal cell staining (1.65% for Gleason 7, 1.26% for Gleason 8-10, compared with 0.42% for Gleason 5-6). The overall specificity of the absence of basal cell staining in the malignant glands for 34betaE12 and p63 was 98.63% and 98.60%, respectively. In 17 cases, both stains revealed total absence of basal cell staining in some benign glands (range, 1%-10%; mean, 3.5%). The overall sensitivity in identifying basal cells in benign glands was 99.48% and 99.44% for 34beta12 and p63, respectively. Basal cell density was higher for 34betaE12 in comparison with p63 (92% vs. 87%). For diagnosing prostate carcinoma in the needle biopsies, p63 is as specific and sensitive Hospital as 34betaE12 and therefore can be used as a complementary basal cell-specific stain for 34betaE12 in difficult cases.     

Prostate-specific antigen, high-molecular-weight cytokeratin (clone 34betaE12), and/or p63: an optimal immunohistochemical panel to distinguish poorly differentiated prostate adenocarcinoma from urothelial carcinoma

An optimal immunohistochemical panel to distinguish poorly differentiated prostate (PCa) from urothelial (UCa) carcinoma was selected from a panel consisting of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), high-molecular-weight cytokeratin (HMWCK), clone 34betaE12, cytokeratin (CK) 7, CK20, p63, and alpha-methylacyl-coenzyme A racemase. The pilot group was composed of poorly differentiated UCa (n = 36) and PCa (n = 42). PSA and PAP stained 95% of PCa vs 0% and 11% of UCa cases, respectively. HMWCK and p63 stained 97% and 92% of UCa vs 2% and 0% of PCa cases respectively. CK7/CK20 coexpression was noted in 50% of UCa cases, whereas 86% of PCa cases were negative with both. A panel of PSA, HMWCK, and p63 was optimal for separating 95% PCa (PSA+/HMWCK and/or p63-) vs 97% UCa (PSA-/HMWCK and/or p63+). This panel was used on 26 diagnostically challenging cases and resolved 81% of cases as UCa vs PCa. The majority of PCa cases retain PSA. Negative PSA with positive HMWCK and/or p63 establishes a diagnosis of UCa.     

前列腺原发性印戒细胞癌的病理诊断和形态发生机制

目的：探讨前列腺原发性印戒细胞癌的组织发生、病理特征和鉴别诊断。方法：在262例经穿刺活检证实的前列腺癌中选出10例印戒细胞癌,用SP法作前列腺特异性抗原（PSA）、前列腺酸性磷酸酶（PAP）、雄激素受体（AR）等9种免疫组织化学标记和AB／PAS,黏液卡红染色,3例作电镜观察,并与10例胃肠道印戒细胞癌作比较。结果：10例中仅1例为纯印戒细胞癌,9例与经典型前列腺癌混合,印戒细胞癌成分均大于癌总量的25％。按形态特征和形成机制,可将印戒细胞分为胞质内空泡或内腔形成和胞质内PSA、PAP分泌物积聚二种类型,二种类型印戒细胞均缺乏胞质内黏液,故不同于消化道印戒细胞癌。结论：原发性印戒细胞癌是来自前列腺腺泡上皮的低分化特殊组织学类型腺癌。在穿刺活检中可以与来自消化道,泌尿道的浸润性或转移性印戒细胞癌鉴别,也不同于放疗或内分泌治疗后经典型前列腺癌的空泡变性。