Annexin A4 Is Involved in Proliferation, Chemo-Resistance and Migration and Invasion in Ovarian Clear Cell Adenocarcinoma Cells

open access (technical)

 ..... CCC is the second most common EOC subtype after HGSC. More than 50% of inactivating mutations in the AT-rich interactive domain 1A gene (ARID1A), almost 40% of activating mutations in the gene encoding the catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA), and microsatellite instability characterize the genetic alterations in CCC [1]. A recent large-cohort study found a pattern in CCC of resistance to standard platinum-based chemotherapy, which offers poor prognosis for patients diagnosed in advanced clinical stages (i.e., International Federation of Gynecology and Obstetrics stages III and IV) [2]. The ratio of CCC among EOC in Japan is reported to be higher than that in Western countries (15–25% and 5–12%, respectively); ethnic or geographical differences in its incidence have also been noticed [3]......

Results

ANXA4 was highly expressed in CCC specimens

Images corresponding to each representative IHC score and a summary of the results are shown in Figure 1A and B. All 52 CCC specimens demonstrated significant staining for ANXA4 (IHC score 5 or 6) without exception, with P<0.05 against all other types of ovarian carcinomas and LMP tumors (Figure 1B). In carcinoma cases, although few cases were available for IHC, all four mucinous carcinomas and two of six endometrioid carcinomas showed high levels (IHC score 4 or greater) of ANXA4 expression. Conversely, all three poorly or undifferentiated carcinomas and 13 of 14 SC expressed no detectable ANXA4. Only two mucinous adenomas were examined, but both of them showed an IHC score 6 expression of ANXA4, presenting a similarity to their malignant counterpart. Only one case of normal premenopausal ovary was available for IHC, but no ovarian components, including surface epithelium, follicles, and stromal tissues, were reactive for ANXA4.....