Endometrial glandular dysplasia: A putative precursor lesion of uterine papillary serous carcinoma. Part II: Molecular features
Endometrial glandular dysplasia: A putative precursor lesion of uterine papillary serous carcinoma. Part II: Molecular features
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DOI：
10.1177/106689690401200405
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发表时间：
2004-10-01
影响因子：
1.2
通讯作者：
Zheng, WX
中科院分区：
文献类型：
--
作者：
Liang, SX;Chambers, SK;Zheng, WX
子宫内膜腺样变(EmGD)可能是子宫乳头状浆液性癌(UPSC)的一种新的形态特征。在这份报告中，我们用激光捕获显微解剖组织样本的杂合性丢失(LOH)方法研究了EmGD中存在的分子变化。选择19个形态显示至少1个EMGD病灶的子宫。其中UPSC 12例，透明细胞癌2例，子宫乳头状浆液性和子宫内膜样癌混合性癌1例，子宫癌肉瘤1例，浆液性子宫内膜上皮内癌1例，子宫内膜息肉2例。利用了7个微卫星DNA标记(位于17p的TP53、位于1p32的D1S211和D1S162、位于17q21的D17S1323、位于17q25的D17S1330、位于5q的D5S346和位于2p的D2S123)。对19例123个激光捕获的显微解剖标本进行了杂合性缺失研究。分析比较良性静息子宫内膜(RE)、EMGD、浆液性EIC和UPSC的LOH频率和模式。在EMGD、浆液性EIC和UPSC等所有类型的皮损中，至少观察到7个标记物中的1个发生LOH。EmGD组LOH发生率为4.2%~31.3%，浆液性EIC组为5.9%~78.6%，UPSC组为7.7%~62.5%。在上述3类病变中，最常见的LOH发生在17P(TP53)和1P(D1S162)。携带TP53和D1S162标记的EmGD组LOH频率显著高于RE组(P<0.05)。以D1S211和D2S123为标记物，EmGD的LOH高于RE，接近统计学意义。然而，与浆液性EIC和UPSC相比，仅TP53基因座的EmGD的LOH发生率显著低于浆液性EIC和UPSC(31.3%对60%以上，p<；0.05)。EmGD组和浆液性EIC/UPSC组与其他染色体标记的LOH频率差异无统计学意义。EMGD病灶与浆液性ETC/UPSC的LOH模式具有高度一致性(p=0.05)。我们的结论是，EmGD在多个染色体上经常表现为LOH，尤其是在17p和1p。EmGD与配对浆液性EIC或UPSC高度一致的LOH频率强烈提示EmGD是UPSC的非癌性前驱病变，可能也是浆液性EIC的前驱病变。EmGD的临床意义有待进一步研究。
Endometrial glandular dysplasia (EmGD) may be a newly defined precursor lesion of uterine papillary serous carcinoma (UPSC) by morphology. In this report, we studied molecular changes present in EmGD by the loss of heterozygosity (LOH) approach using laser capture microdissected tissue samples. Nineteen uteri showing at least 1 focus of EmGD by morphology were selected. These cases were 12 UPSC, 2 clear cell carcinomas, I mixed uterine papillary serous and endometrioid carcinoma, 1 uterine carcinosarcoma, 1 serous endometrial intraepithelial carcinoma (EIC), and 2 EmGD involving endometrial polyps. Seven microsatellite polymorphic DNA markers (TP53 at 17p, D1S211, and D1S162 at 1p32, D17S1323 at 17q21, D17S1330 at 17q25, D5S346 at 5q, and D2S123 at 2p) were utilized. A total of 123 laser-captured microdissection samples from 19 cases was studied with LOH method. The frequencies and patterns of LOH were analyzed and compared among benign resting endometrium (RE), EmGD, serous EIC, and UPSC. LOH was observed for at least 1 of the 7 markers in all categories of lesions, EmGD, serous EIC, and UPSC. The frequency of LOH for EmGD ranged from 4.2% to 31.3%; the range for serous EIC was 5.9% to 78.6%; and that for UPSC was 7.7% to 62.5%. The most frequent LOH in the 3 above-cited categories of lesions was identified at 17p (TP53) and 1p (D1S162). The frequency of LOH in EmGD with markers of TP53 and D1S162 was significantly higher than in RE (p < 0.05). With markers of D1S211 and D2S123, LOH in EmGD was higher than RE, approaching to a statistically significant level. Compared with foci of serous EIC and UPSC, however, the rate of LOH in EmGD was significantly lower only with TP53 locus (31.3% vs more than 60%, p < 0.05). The difference of LOH frequency with other chromosomal markers between EmGD and serous EIC/UPSC did not reach a statistically significant level. A significantly high concordant LOH pattern was found between foci of EmGD and serous ETC/UPSC (p = 0.05). We conclude that EmGD frequently shows LOH at multiple chromosomal loci, particularly at 17p and 1p. Significantly high concordant LOH frequency between EmGD and paired serous EIC or UPSC strongly suggests that EmGD is a noncancerous precursor lesion of UPSC, probably also of serous EIC. The clinical significance of EmGD needs further studies.