title: HER2-positive mucinous adenocarcinomas of the ovary have an expansile invasive pattern associated with a favorable prognosis.
abstract: 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.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: HER2; Mucinous adenocarcinoma; ovary; prognostic factor