Acs Geza, Pasha Theresa, Zhang Paul J
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
Int J Gynecol Pathol. 2004 Apr;23(2):110-8. doi: 10.1097/00004347-200404000-00004.
The Wilms' tumor gene WT1 plays complex roles in the development of the organs of the genitourinary tract and mesothelium, as well as Wilms' tumors. Although its biologic role is still unclear, most serous carcinomas of the ovary and peritoneum, mesotheliomas, and Wilms' tumor have been shown to express WT1. A recent study, however, found no WT1 expression in serous carcinomas of the endometrium, suggesting that WT1 could be useful in identifying the primary site of serous carcinomas. We examined the expression of WT1 and p53 by immunohistochemistry in 69 cases of endometrial carcinoma (35 endometrioid, 18 clear cell, 16 serous), 68 cases of ovarian carcinoma (28 serous, 11 endometrioid, 18 clear cell, and 11 mucinous), 14 fallopian tube carcinomas (12 serous, 2 endometrioid), and 20 primary peritoneal serous carcinomas. WT1 nuclear reactivity of any extent and intensity was considered positive. Immunohistochemical stains were evaluated semiquantitatively using a four-tiered scale. Among endometrial carcinomas, WT1 immunoreactivity was seen in 10 of 16 serous, but in none of 35 endometrioid or 18 clear cell carcinomas. Among ovarian tumors, WT1 expression was seen in 24 of 28 serous and 4 of 18 clear cell carcinomas, but in none of 11 endometrioid and 11 mucinous tumors. All 12 serous carcinomas but none of 2 endometrioid carcinomas of the fallopian tube were positive for WT1. WT1 expression was seen in 19 of 20 serous primary peritoneal carcinomas. The difference in WT1 expression was highly significant between serous and other types of tumors in all sites (p<0.0001, chi-square test), although the level of WT1 expression was significantly different among serous carcinomas arising at different sites (p<0.0001, Kruskal-Wallis test). A significant positive correlation was found between the level of p53 and WT1 expression in all carcinomas combined (r = 0.3935, p<0.0001, Spearman test), but when only serous carcinomas were analyzed, the correlation between p53 and WT1 expression levels did not reach statistical significance. Our results suggest that WT1 expression in epithelial tumors of the female genital tract may be related to cell differentiation and histologic subtypes of carcinomas, rather than to primary site of origin.
肾母细胞瘤基因WT1在泌尿生殖道和间皮器官以及肾母细胞瘤的发育中发挥着复杂作用。尽管其生物学作用仍不清楚,但大多数卵巢和腹膜浆液性癌、间皮瘤以及肾母细胞瘤均已显示表达WT1。然而,最近一项研究发现子宫内膜浆液性癌中无WT1表达,这表明WT1可能有助于确定浆液性癌的原发部位。我们采用免疫组织化学方法检测了69例子宫内膜癌(35例子宫内膜样癌、18例透明细胞癌、16例浆液性癌)、68例卵巢癌(28例浆液性癌、11例子宫内膜样癌、18例透明细胞癌和11例黏液性癌)、14例输卵管癌(12例浆液性癌、2例子宫内膜样癌)以及20例原发性腹膜浆液性癌中WT1和p53的表达。WT1核反应性无论程度和强度如何均视为阳性。免疫组织化学染色采用四级评分法进行半定量评估。在子宫内膜癌中,16例浆液性癌中有10例可见WT1免疫反应性,但35例子宫内膜样癌和18例透明细胞癌中均未见到。在卵巢肿瘤中,28例浆液性癌中有24例以及18例透明细胞癌中有4例可见WT1表达,但11例子宫内膜样癌和11例黏液性肿瘤中均未见到。12例输卵管浆液性癌均为WT1阳性,而2例输卵管子宫内膜样癌均为阴性。20例原发性腹膜浆液性癌中有19例可见WT1表达。尽管不同部位的浆液性癌之间WT1表达水平存在显著差异(p<0.0001,Kruskal-Wallis检验),但在所有部位,浆液性肿瘤与其他类型肿瘤之间WT1表达差异均具有高度显著性(p<0.0001,卡方检验)。在所有联合分析的癌中,p53水平与WT1表达之间存在显著正相关(r = 0.3935,p<0.0001,Spearman检验),但仅分析浆液性癌时,p53与WT1表达水平之间的相关性未达到统计学显著性。我们的结果表明,女性生殖道上皮性肿瘤中WT1表达可能与癌的细胞分化和组织学亚型有关,而非与原发部位有关。