摘要目的：探讨Ca15-3在Paget病鉴别诊断中的价值。方法：对11例阴囊Paget病回顾性地做Ca15-3、EMA、CEA和HMB45免疫组化染色，并以4例Bowen病和1例恶性黑色素瘤做对照。结果：Ca15-3、EMA在Paget病和大、小汗腺及皮脂腺均有较强的表达，4例Bowen病均无Ca15-3表达，但其中2例有EMA表达。CEA在6例(54.5%)Paget病中有表达。HMB45只在恶性黑色素瘤中表达。结论：Ca15-3在Paget细胞的相对特异性表达提示它可作为Paget病与Bowen病鉴别诊断的标志物，其对诊断的敏感性与EMA相同，但特异性高于EMA。同时还说明Paget病的发生可能与汗腺有关。

中国图书资料分类法分类号R711.72

The value of Ca15-3 in differential diagnosis of Paget's disease

KONG Xiang-Tian^#， TU Ping, LI Jing-Xian, ZENG Li, XIA Tong-Li, GUO Ying-Lu

(#Institute of Urology, the First Hospital, Beijing Medical University, Beijing100034)

MeSHPaget's disease, extramammary/diagCa15-3^☆Diagnosis, differentialBowen's disease/diag

ABSTRACTObjective: To probe the value of Ca15-3, an antibody to human milk-fat globule membrane and to the membranous component of mammary cancer cells, in differential diagnosis of Paget's disease.Methods: A retrospective study of 11 cases of scrotal Paget's disease from 1984 to 1997 in our hospital was carried out, and 4 cases of Bowen's disease and 1 of malignant melanoma were studied as control. Ca15-3, EMA, CEA, HMB45 were immunostained in all cases.Results: Paget's cells stained strongly with antibodies Ca15-3 and EMA, and staining with Ca15-3 and EMA was also observed in the ductal and secretory portions of the eccrine and apocrine glands, and in the sebaceous gland cells. Staining with the antibody CEA was observed in 54.5% of the cases in Paget's disease, and none in Bowen's disease. Expression of EMA was also observed in 2 out of 4 cases in Bowen's disease. HMB45 was the only antigen expressed in malignant melanoma.Conclusion: Ca15-3 was specifically expressed in Paget's cells. This result demonstrated that Ca15-3 can be used as a marker in the differential diagnosis between Paget's disease and Bowen's disease. It has the same sensitivity as EMA and higher specificity than EMA in differential diagnosis. The coexpression of Ca15-3 in Paget cells and in cutaneous adenexal organs suggests that the origin of Paget cells may be the secretory cells of sweat glands.

(J Beijing Med Univ, 1999,31:426-428)

在Paget病病理诊断中,除常规HE染色外，还发现Paget细胞表达许多上皮和癌基因产物，如低分子量细胞角蛋白、上皮膜抗原(EMA)、癌胚抗原(CEA)和Ca15-3等^［1］。但是，需与Paget病相鉴别的Bowen病也表达其中部分产物,所以找到Paget细胞特异的标志物对鉴别诊断十分必要。我们对我院1984～1997年间收治的11例阴囊Paget病全部做Ca15-3、EMA、CEA和HMB45 4种抗体的免疫组化染色，并以4例Bowen病和1例恶性黑色素瘤做对照研究，发现Ca15-3在Paget细胞呈相对特异性表达。报告如下。

1材料与方法

对1984～1997年间我院收治的11例阴囊Paget病进行回顾性研究，复查病理切片并做免疫组化染色。选取4例Bowen病和1例皮肤恶性黑色素瘤(以下简称恶黑)做对照研究。所用抗体鼠抗人Ca15-3(1∶50)、EMA(1∶100)、HMB45(1∶75)和CEA(工作液)均为美国Zymed公司产品，由北京中山生物制品公司提供。SP法染色。采用微波进行抗原修复。设阳性和阴性对照。染色结果根据强度判断为－～+++不等。

2结果

2.1上述抗体在表皮及其附属器中的表达

Ca15-3在正常皮肤的大、小汗腺导管和分泌腺的管腔表面和分泌上皮细胞胞浆表达较强（++～+++, 图1）, 而导管的基底细胞和分泌腺的肌上皮细胞无表达。皮脂腺有较强表达。EMA的表达情况同Ca15-3, 但表达强度强于Ca15-3（表1）。CEA只在小汗腺导管和分泌腺的管腔表面有弱表达（+/－）。HMB45只在表皮黑色素细胞表达。

图1皮肤小汗腺管腔表面和分泌上皮Ca15-3有较强的表达×50

Figure 1Strong expression of Ca15-3 in eccrine sweat glands×50

表1正常表皮及皮肤附属器几种标志物的表达

Table 1Expression of antibodies in normal epidermis and its adenexal structures

Ca15-3⁺ EMA⁺ CEA⁺ HMB45⁺ Epidermal keratinocytes － － － － Melanocytes － － － ＋＋ Eccrine sweat glands Ducts luminal surface ++ +++ +/－ － luminal cells ++ +++ +/－ － basal cells － － － － Secretary elements luminal surface ++ +++ +/－ － secretary cells ++ +++ +/－ － myoepithelial cells － － － － Apocrine sweat glands Ducts luminal surface +++ +++ － － luminal cells +++ +++ － － basal cells － － － － Secretary elements luminal surface +++ +++ － － secretary cells +++ +++ － － myoepithelial cells － － － － Sebaceous glands +++ +++ － －

+, immunohistochemical staining positive.2.2皮肤肿瘤免疫组织化学染色结果

本组皮肤肿瘤Ca15-3和EMA在11例Paget病中均表达(图2)，其中包括1例转移至腹股沟淋巴结的Paget病(图3)。而CEA只在其中的6例中有表达(54.5%)。EMA在Paget病和Bowen病间有交叉反应，4例Bowen病中2例有EMA的表达。而Ca15-3在Bowen病呈阴性反应。HMB45只在恶黑中表达(表2)。

图2Paget细胞Ca15-3阳性表达，而角化上皮细胞阴性×50

Figure 2Staining is positive for Ca15-3 in Paget cells and negative in keratinocytes×50

表2皮肤肿瘤免疫组织化学染色结果

Table 2Immunohistochemical staining results of skin tumors

Tumors Cases Ca15-3⁺ EMA⁺ CEA⁺ HMB45⁺ Paget's disease 11 11/11 11/11 6/11 0/11 Bowen's disease 4 0/4 2/4 0/4 0/4 Malignant melanoma 1 0/1 0/1 0/1 1/1

3讨论

在皮肤肿瘤中，Paget病、Bowen病和恶黑是需要仔细进行鉴别的，尤其是Paget样Bowen病(Pagetoid Bowen's disease)、表皮内表浅扩散的恶黑(Intraepidermal superficial spreading malignant melanoma)和Paget样无色素性恶黑(Pageto