Kim Sang Kyum, Cho Nam Hoon
Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
Int J Clin Exp Pathol. 2014 Jun 15;7(7):4222-30. eCollection 2014.
Ovarian primary mucinous adenocarcinomas (MACs) are refractory to conventional therapy. Biomarkers for ovarian MAC could facilitate prognosis and targeted therapy, but are not currently available. The expression of human epidermal growth factor 2 (HER-2) has been linked to enhanced survival of MAC patients and may hold potential as a biomarker, but this potential has not been sufficiently investigated. In this study, we examined the clinicopathological features of 46 cases of MAC and 36 cases of patients with mucinous borderline tumors (MBTs). The expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 were measured by immunohistochemistry and fluorescent in situ hybridization (FISH). Next, we compared the clinicopathological characteristics according to the HER2 expression profile. MBTs of the endocervical type tended to have simultaneous ER and PR expression (P = 0.0028) while MACs rarely showed ER or PR expression. HER2 expression was observed in 14 out of the 46 MACs (37.84%) and in none of the MBTs (P = 0.0002). HER2-positive MACs occurred approximately 10 years earlier than HER2-negative MACs (35.21 ± 4.768 years compared to 46.78 ± 1.977 years; P = 0.0105). All HER2-positive MACs demonstrated an expansile invasive pattern, while all MACs with infiltrative invasion pattern were HER2-negative (P = 0.0406). Kaplan-Meier survival analysis demonstrated a tendency for improved overall survival in HER2-positive MACs compared to HER2-negative MACs (P = 0.0389). In conclusion, HER2 overexpression in ovarian MACs is associated with an expansile, but not an infiltrative, invasion pattern and a favorable prognosis. Therefore, we suggest that HER2 may be a practical marker for histopathological categorization and a prognostic marker in ovarian MACs.
卵巢原发性黏液腺癌(MAC)对传统治疗具有耐药性。卵巢MAC的生物标志物有助于预后评估和靶向治疗,但目前尚无可用的标志物。人表皮生长因子2(HER-2)的表达与MAC患者的生存期延长有关,可能具有作为生物标志物的潜力,但这一潜力尚未得到充分研究。在本研究中,我们检查了46例MAC患者和36例黏液性交界性肿瘤(MBT)患者的临床病理特征。通过免疫组织化学和荧光原位杂交(FISH)检测雌激素受体(ER)、孕激素受体(PR)和HER2的表达。接下来,我们根据HER2表达谱比较了临床病理特征。宫颈内膜型MBT倾向于同时表达ER和PR(P = 0.0028),而MAC很少表达ER或PR。46例MAC中有14例观察到HER2表达(37.84%),而MBT中均未观察到HER2表达(P = 0.0002)。HER2阳性MAC的发病时间比HER2阴性MAC早约10年(分别为35.21±4.768岁和46.78±1.977岁;P = 0.0105)。所有HER2阳性MAC均表现为膨胀性浸润模式,而所有具有浸润性浸润模式的MAC均为HER2阴性(P = 0.0406)。Kaplan-Meier生存分析表明,与HER2阴性MAC相比,HER2阳性MAC的总生存期有改善趋势(P = 0.0389)。总之,卵巢MAC中HER2过表达与膨胀性而非浸润性浸润模式及良好预后相关。因此,我们认为HER2可能是卵巢MAC组织病理学分类的实用标志物和预后标志物。