Original contributionProgressive loss of selenium-binding protein 1 expression correlates with increasing epithelial proliferation and papillary complexity in ovarian serous borderline tumor and low-grade serous carcinoma
Introduction
Serous borderline tumor of the ovary has been a subject of debate because of its uncertain biological behavior. Most participants at the Borderline Ovarian Tumor Workshop held in Bethesda, MD, in 2003 agreed on the following definitions [1]. Serous borderline tumor (SBOT) is characterized by the formation of hierarchical structures consisting of primary and secondary papillae. The designation of SBOT requires the presence of hierarchical papillae in greater than 10% of a cystic neoplasm. Tumors with less hierarchical papillae are categorized as cystadenoma. Micropapillary SBOT (M-SBOT) refers to an SBOT showing at least one 5-mm uninterrupted focus of micropapillary or cribriform pattern. Tumors with smaller micropapillae are classified as SBOT. Destructive invasion in a borderline tumor indicates the presence of a carcinoma. The invasive carcinoma associated with SBOT is usually low-grade serous carcinoma (LGSC). SBOT, M-SBOT, and LGSC frequently show a spectrum of histologic changes ranging from flat cyst wall, hierarchical structures (with primary papillae branching into secondary papillae), micropapillae, and invasive carcinoma. The wide range of histologic changes provides an ideal system to study their biological relationship.
Recent genetic and molecular studies suggest a stepwise progression from serous cystadenoma, SBOT, M-SBOT, to LGSC; this pathway is characterized by mutations in BRAF and KRAS [2], [3]. In general, the development of tumor requires alterations of multiple growth control genes. Up to now, however, only a limited number of molecular changes have been known to occur in the pathway of SBOT, M-SBOT, and LGSC.
Selenium-binding protein 1 (SELENBP1) has been shown to be expressed differentially between normal and neoplastic tissues [4]. SELENBP1 is a cellular protein that binds to exogenously administered selenium. Numerous reports have described a relationship between insufficient selenium intake and increased risk of cancer [5], [6], [7]. SELENBP1 has been suggested to mediate the anticancer action of selenium as it is decreased in cancers of the prostate, the lung, and the colon [8], [9], [10]. By membrane proteome profiling analysis, SELENBP1 was found to be the most significantly down-regulated protein in ovarian cancer cells [4]. Down-regulation of SELENBP1 was also demonstrated in ovarian carcinomas in the experimental laying hens [11]. To date, however, no systematic studies have been carried out concerning the expressions of SELENBP1 in SBOT, M-SBOT, and LGSC.
In this study, we examined the expressions of SELENBP1 in a wide spectrum of histologic components within SBOT, M-SBOT, and LGSC.
Section snippets
Materials and methods
We retrieved a total of 62 cases of SBOT, 11 of M-SBOT, and 7 of LGSC from our institutional pathology archives during a period between 1993 and 2005. Of these cases, 68 were the result of total hysterectomy with bilateral salpingo-oophorectomy, and 12 were from salpingo-oophorectomy or cystectomy alone. The original pathology reports were reviewed for gross characteristics of the tumors. Archival hematoxylin and eosin slides were evaluated to confirm the diagnosis. SBOT, M-SBOT, and LGSC were
Results
The patients' age ranged from 27 to 82 years (mean, 48.5 years) in SBOT, 37 to 72 years (mean, 51.6 years) in M-SBOT, and 40 to 76 years (mean, 52.5 years) in LGSC. Although there was a tendency for an average older age from SBOT, M-SBOT, to LGSC, the difference did not reach a statistical significance (P = .242). A significant difference in tumor size was seen in the following order: SBOT (from 4.8 to 15.4 cm; mean, 7.2 cm) < M-SBOT (from 8.0 to 21.5 cm; mean, 10.8 cm) < LGSC (from 10.5 to
Discussion
Within SBOT, M-SBOT, and LGSC, the degree of epithelial proliferation and papillary complexity in an increasing order ranged from flat cyst wall, primary papillae, secondary papillae, micropapillae, and invasive components. Our study showed a gradual loss of SELENBP1 expression associated with increasing epithelial proliferation and papillary complexity within SBOT, M-SBOT, and LGSC. The highest level of SELENBP1 expression was seen in flat cyst wall and primary papillae of the hierarchical
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