Discrepant clinicopathologic characteristics and HE4 performance in type I and type II epithelial ovarian cancer

Recent studies have demonstrated that epithelial ovarian cancer (EOC) are factual several different diseases. A two-tier system divides EOC into type I and type II EOC. HE4 has been used as a complementary biomarker for diagnosing EOC. This study aimed to evaluate the different clinicopathologic characteristics and HE4 expression levels in types I and II EOCs. This retrospective study included 127 EOC patients. Data related to patient demographics, cancer stages, grades, histology, operation procedures, residual disease, adjuvant chemotherapy, recurrence, and survival were collected. A total of 134 ovarian carcinoma tissue specimens and 40 matching borderline ovarian tumor specimens were chosen from the pathology department archives. Immunohistochemistry was used to assess HE4 expression in EOC and borderline ovarian tumor tissue specimens. Of the 127 patients, there were 42 type I EOC patients (7 low grade serous carcinomas, 8 mucinous carcinomas, 12 low grade endometrioid carcinomas and 15 clear cell carcinomas) and 85 type II EOC patients (83 high grade serous carcinomas and 2 high grade endometrioid carcinomas). The median followed-up time was 18.3 months. There were significant differences between the two types of EOC in terms of the menopausal state, FIGO stage and pathological differentiation, but there were no differences in the residual tumor and chemotherapy treatment. In type I EOC, the median follow-up time was 31 months and the median progression-free survival was 72 months (95% CI: 40.34-103.66). There were 15 (35.7%) relapsed or progressive patients. In type II EOC, the median follow-up time was 17 months (0-60 m), and the median progression-free survival was 27 months (95% CI: 17.83-36.17). There were 47 (55.3%) relapsed or progressive patients. There was a significant difference between the two types of EOCs in terms of progression-free survival (P< 0.001). Among the 44 type I specimens, 25 demonstrated positive expression of HE4 (56.8%). In contrast, 78 (86.7%) type II EOC demonstrated positive expression levels. There was a significant difference between type I and type II EOCs in terms of HE4 expression. Additionally, there was a significant difference between high grade serous carcinoma and borderline serous tumor, but no difference was observed between low grade serous carcinoma and borderline serous tumor or other types of EOC and corresponding borderline tumors. The different clinicopathologic characteristics between type I and type II EOC indicate that the two-tier EOC system reasonable and reliable. HE4 would be a powerful biomarker to distinguish type II EOC from borderline tumors but it is less useful in type I EOC. Type I EOC is generated from the corresponding borderline tumor.