Davies Suzy, Holmes Anna, Lomo Lesley, Steinkamp Mara P, Kang Huining, Muller Carolyn Y, Wilson Bridget S
Departments of Obstetrics and Gynecology (S.D., C.Y.M.) Pathology (A.H., M.P.S., L.L., B.S.W.) Internal Medicine (H.K.) Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM (H.K., B.S.W).
Int J Gynecol Pathol. 2014 Jul;33(4):402-10. doi: 10.1097/PGP.0000000000000081.
Ovarian cancer is the leading cause of death from gynecologic cancers in the United States. Failure may be due to variable expression and/or complex interactions of growth factor receptors in individual tumors. As ErbB3-MET cooperativity is implicated in solid tumor resistance to EGFR/ErbB2 inhibitors, we evaluated expression of MET and all 4 ErbB family members in ovarian cancers. Tissue arrays were prepared from archival formalin-fixed paraffin-embedded tumor samples, including 202 ovarian carcinomas (Stage I-IV) and controls. Of 202 patient samples, only 25% were positive for EGFR and 35% for ErbB2 expression. ErbB3, ErbB4, and MET showed marked expression in 76%, 98%, and 96% of cases. Consistent with high incidence, there was no significant correlation for expression of ErbB3, ErbB4, or MET with outcome. On the basis of their high expression in the majority of cases, inhibitors targeting ErbB3, ErbB4, and/or MET may be broadly applicable as therapeutic agents in this disease.
卵巢癌是美国妇科癌症死亡的主要原因。治疗失败可能是由于个体肿瘤中生长因子受体的表达可变和/或复杂相互作用。由于ErbB3-MET协同作用与实体瘤对EGFR/ErbB2抑制剂的耐药性有关，我们评估了MET和所有4种ErbB家族成员在卵巢癌中的表达。组织芯片由存档的福尔马林固定石蜡包埋肿瘤样本制备而成，包括202例卵巢癌（I-IV期）和对照。在202例患者样本中，仅25%的EGFR呈阳性，35%的ErbB2表达呈阳性。ErbB3、ErbB4和MET在76%、98%和96%的病例中呈显著表达。与高发生率一致，ErbB3、ErbB4或MET的表达与预后无显著相关性。基于它们在大多数病例中的高表达，靶向ErbB3、ErbB4和/或MET的抑制剂可能作为治疗该疾病的药物广泛适用。
