Fulop V, Mok S C, Genest D R, Szigetvari I, Cseh I, Berkowitz R S
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Reprod Med. 1998 Feb;43(2):101-10.
To determine the expression of bcl-2, c-myc, c-fms and c-erbB-2 oncoproteins in normal placentas, partial and complete hydatidiform moles, and choriocarcinomas and to examine the possible presence of mutations in the K-ras gene in complete moles and choriocarcinomas.
The expression of the above oncoproteins was determined immunohistochemically by specific antibodies for these proteins on formalin-fixed paraffin sections of 18 normal placentas, 17 partial moles, 25 complete moles and 11 choriocarcinomas. This was followed by polymerase chain reaction analysis (exons 12 and 13) of K-ras gene for possible mutations in complete moles and choriocarcinomas.
Expression of c-fms oncoprotein appeared confined to the cytoplasm of syncytiotrophoblastic cells. The c-fms protein staining intensity of the syncytiotrophoblastic layer showed no significant difference among the four gestational tissues. c-erbB-2 antibody expression was confined to the cellular membrane of the extravillous trophoblast. When compared with normal placenta or partial mole, the expression of c-erbB-2 protein was significantly stronger in complete mole (P < .0001 and P < .0001, respectively) and choriocarcinoma (P < .0001 and P < .0001, respectively). Expression of bcl-2 protein was significantly stronger in the syncytiotrophoblast in complete mole and choriocarcinoma as compared to both normal placenta and partial mole (P < .0001 and P < .0001, respectively). Staining of c-myc of the syncytiotrophoblastic layer was significantly stronger in placenta, complete mole and choriocarcinoma than in partial mole (P < .0001, P < .0001 and P < .0001, respectively). Mutation in K-ras gene was not found in any of the 22 complete moles or 11 choriocarcinomas examined.
Our data suggest that c-myc, c-erbB-2, c-fms and bcl-2 oncoproteins may be important in the pathogenesis of complete mole and choriocarcinoma. However, while both complete mole and choriocarcinoma were characterized by overexpression of c-myc, c-erbB-2 and bcl-2, partial mole generally did not strongly express these three oncoproteins.
测定bcl-2、c-myc、c-fms和c-erbB-2癌蛋白在正常胎盘、部分性和完全性葡萄胎及绒毛膜癌中的表达,并检测完全性葡萄胎和绒毛膜癌中K-ras基因是否可能存在突变。
通过针对这些蛋白的特异性抗体,采用免疫组织化学方法在18例正常胎盘、17例部分性葡萄胎、25例完全性葡萄胎和11例绒毛膜癌的福尔马林固定石蜡切片上测定上述癌蛋白的表达。随后对完全性葡萄胎和绒毛膜癌进行K-ras基因的聚合酶链反应分析(外显子12和13),以检测可能的突变。
c-fms癌蛋白的表达似乎局限于合体滋养层细胞的细胞质。合体滋养层的c-fms蛋白染色强度在四种妊娠组织中无显著差异。c-erbB-2抗体的表达局限于绒毛外滋养层的细胞膜。与正常胎盘或部分性葡萄胎相比,c-erbB-2蛋白在完全性葡萄胎(分别为P <.0001和P <.0001)和绒毛膜癌(分别为P <.0001和P <.0001)中的表达明显更强。与正常胎盘和部分性葡萄胎相比,bcl-2蛋白在完全性葡萄胎和绒毛膜癌的合体滋养层中的表达明显更强(分别为P <.0001和P <.0001)。合体滋养层的c-myc染色在胎盘、完全性葡萄胎和绒毛膜癌中明显强于部分性葡萄胎(分别为P <.0001、P <.0001和P <.0001)。在所检测的22例完全性葡萄胎和11例绒毛膜癌中均未发现K-ras基因的突变。
我们的数据表明,c-myc、c-erbB-2、c-fms和bcl-2癌蛋白可能在完全性葡萄胎和绒毛膜癌的发病机制中起重要作用。然而,虽然完全性葡萄胎和绒毛膜癌均以c-myc、c-erbB-2和bcl-2的过表达为特征,但部分性葡萄胎通常不强烈表达这三种癌蛋白。