Biomarker expression in normal fimbriae: Comparison of high- and low-grade serous ovarian carcinoma

Abstract

The objective of this study was to assess the difference in fimbriae of high- and low-grade ovarian serous carcinoma (OSC). The fimbriae of normal appearance [without serous tubal intraepithelial carcinoma (STIC)] from 28 patients with high-grade OSCs and 24 patients with low-grade OSCs were assessed for the expression of 6 markers [E-cadherin, matrix metalloproteinase-2 (MMP-2), phospho-AKT (pAKT), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and p53] using immunohistochemistry. Sectioning and extensively examining the fimbria (SEE-FIM) was performed to exclude fimbrial involvement for all the cases. The immunostaining levels of pAKT and COX-2 were significantly higher in the fimbriae of normal appearance from high-grade OSCs compared with low-grade OSCs (61 vs. 8% and 71 vs. 21%; P=0.005 and 0.007, respectively). The immunostaining of E-cadherin was significantly higher in the fimbriae of low-grade OSCs compared with high-grade OSCs (83 vs. 21%; P= 0.003). The remaining 3 markers (MMP-2, VEGF and p53) had similar expression in low- and high-grade OSCs (21 vs. 13%; 25 vs. 21%; and 14 vs. 8%; P=0.78, 0.86 and 0.82, respectively). Our results suggest marked biological differences in the behavior of the fimbriae in high- and low-grade OSCs and indicate that proliferation, cell adhesion and the inflammatory microenvironment of fimbriae in high-grade OSCs without STIC had changed prior to p53 mutation.

Figure 1

Cases of fimbrial epithelial cells in (A) high-grade and (B) low-grade OSC exhibiting strong nuclear positivity for pAKT. The high-grade lesions consistently showed more staining than the low-grade tumors. Cases of fimbrial epithelial cells in (C) high-grade and (D) low-grade OSC exhibiting strong nuclear positivity for E-cadherin. The high-grade lesions consistently showed less staining than the low-grade tumors. Cases of fimbrial epithelial cells in (E) high-grade and (F) low-grade OSC exhibiting strong nuclear positivity for COX-2. The high-grade lesions consistently showed more staining than the low-grade tumors. OSC, ovarian serous carcinoma; pAKT, phospho-AKT; COX-2, cyclooxygenase-2.