Gaggero G, Sola S, Mora M, Fulcheri E
Servizio di Anatomia Patologica dell'Università di Genova.
Pathologica. 2003 Aug;95(4):185-91.
Cdx2 gene belongs to the homeobox caudal gene family and it is located, in humans, on the 13q12.3 chromosome; in particular it codifies for a specific nuclear transcription factor which induces intestinal epithelium development, differentiation and preservation. Cdx2 expression in the human embryo can be observed in the intestinal epithelium starting from the sixth week of gestation. In the foetus and in adults it is observed in the whole enteric tube from the duodenum to the anal canal. Because of its organ specificity, cdx2 is an important marker for metastatic neoplastic lesions. Cdx2 is expressed in intestinal metaplasia and it is focally positive in adenocarcinomas of intestinal type of the stomach, pancreas and gall bladder as well as in ovarian mucinous adenocarcinomas. FINALITY OF THE STUDY: The aim of our study is to detect cdx2 positivity, with evaluation of its characteristics and expression, in ovarian mucinous cistoadenomas.
We examined cdx2 expression in 50 ovarian mucinous cistoadenomas (mean age between 17 and 85), 19 of which were localised in the right ovary while 31 in the left one. Standard staining techniques (H&E), histochemistry (AB-PAS) ed immunohistochemistry with monoclonal antibodies against cdx2 (Biogenex/Menarini cdx2-88, batch MU3920402XS) were performed on formalin fixed and paraffin embedded material. For each case two samples were analysed.
Morphological evaluation of the 50 benign mucinous tumours distinguished 47 of endocervical type and 3 of intestinal type. These data were also confirmed by characterisation of mucin profile by AB-PAS staining. Using anti-cdx2 antibodies tumours of endocervical type were negative, while 3 intestinal type tumours were positive. In particular 2 cases presented diffuse nuclear positivity, while in one positivity was only focal.
Until today only two studies deal with cdx2 expression in mucinous ovarian tumours: 5 and 14 cases strong respectively. In the former, cdx2 expression was positive in all cases (100% positivity--5/5), in the latter cdx2 expression was positive in 64% of cases (9/14). In order to explain the lack of consistency in these data one must analyse ovarian mucinous tumours in detail. These neoplasms are divided into two subtypes: endocervical type and intestinal type. Distinction between these two types is near to impossible in malignant tumours, difficult in borderline tumours while it becomes easy in benign ones. Among benign tumours, endocervical type tumours are the majority, while intestinal type are much more infrequent. Our 50 case strong casistic is sufficiently ample to include 3 cases of intestinal type, all of which are cdx2 positive, compared to a complete negativity in the remaining 47 tumours clearly of endocervical type. We believe that the lack of consistency between the aforementioned studies is probably due to the fact that neither work contemplates the subdivision in intestinal and endocervical types. It is hence possible to hypothesise a selective and specific correlation between cdx2 positivity and the intestinal type epithelial component of ovarian tumours.
Cdx2基因属于同源框尾基因家族,在人类中,它位于13号染色体长臂1区2带3亚带(13q12.3);具体而言,它编码一种特定的核转录因子,该因子可诱导肠上皮的发育、分化和维持。在人类胚胎中,从妊娠第6周开始,可在肠上皮中观察到Cdx2的表达。在胎儿和成人中,从十二指肠到肛管的整个肠道中均可观察到Cdx2的表达。由于其器官特异性,Cdx2是转移性肿瘤病变的重要标志物。Cdx2在肠化生中表达,在胃、胰腺和胆囊的肠型腺癌以及卵巢黏液腺癌中呈局灶性阳性。
我们研究的目的是检测卵巢黏液性囊腺瘤中Cdx2的阳性情况,并评估其特征和表达。
我们检测了50例卵巢黏液性囊腺瘤(平均年龄在17至85岁之间)中Cdx2的表达,其中19例位于右侧卵巢,31例位于左侧卵巢。对福尔马林固定、石蜡包埋的材料进行标准染色技术(苏木精-伊红染色,H&E)、组织化学(阿尔辛蓝-过碘酸雪夫染色,AB-PAS)以及使用抗Cdx2单克隆抗体(Biogenex/Menarini cdx2-88,批次MU3920402XS)的免疫组织化学检测。对每个病例分析两个样本。
对50例良性黏液性肿瘤的形态学评估显示,47例为宫颈内膜型,3例为肠型。AB-PAS染色对黏液成分的特征分析也证实了这些数据。使用抗Cdx2抗体检测,宫颈内膜型肿瘤均为阴性,而3例肠型肿瘤呈阳性。具体而言,2例呈现弥漫性核阳性,1例仅为局灶性阳性。
到目前为止,仅有两项研究涉及黏液性卵巢肿瘤中Cdx2的表达,分别为5例和14例。在前者中,所有病例(100%阳性,5/5)的Cdx2表达均为阳性,在后者中,64%的病例(9/14)Cdx2表达为阳性。为了解释这些数据缺乏一致性的原因,必须对卵巢黏液性肿瘤进行详细分析。这些肿瘤分为两种亚型:宫颈内膜型和肠型。在恶性肿瘤中,区分这两种类型几乎不可能,在交界性肿瘤中困难,而在良性肿瘤中则容易。在良性肿瘤中,宫颈内膜型肿瘤占大多数,而肠型则更为少见。我们50例的病例组足够大,其中包括3例肠型肿瘤,所有这些肿瘤的Cdx2均为阳性,而其余47例明显为宫颈内膜型的肿瘤则完全为阴性。我们认为,上述研究之间缺乏一致性可能是由于两项研究均未考虑将肿瘤细分为肠型和宫颈内膜型。因此,可以假设Cdx2阳性与卵巢肿瘤的肠型上皮成分之间存在选择性和特异性的相关性。