Elsevier

Human Pathology

Volume 41, Issue 2, February 2010, Pages 255-261
Human Pathology

Original contribution
Progressive 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

https://doi.org/10.1016/j.humpath.2009.07.019Get rights and content

Summary

Ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma often show a spectrum of histologic components with increasing epithelial proliferation and papillary complexity from flat cyst wall, hierarchical structures (with primary papillae branching into secondary papillae), micropapillae, and invasive carcinoma. Although tremendous research has been carried out to elucidate the causes of these tumors, the pathogenesis remains unclear. Literature has described a relationship between insufficient selenium intake and increased risk of cancer. The anticancer action of selenium has been suggested to be mediated by selenium-binding protein 1 as selenium-binding protein 1 is decreased in several cancers. The aim of the study was to examine by immunohistochemistry the expression of selenium-binding protein 1 in the various histologic components within ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma. Our study consisted of 62 cases of ovarian serous borderline tumor, 11 of micropapillary serous borderline tumor, and 7 of low-grade serous carcinoma. Review of archival slides showed flat cyst wall in 69 cases, primary and secondary papillae of hierarchical structures in 75 cases, micropapillae in 26 cases, microinvasion in 1 case, and frankly invasive carcinoma in 7 cases. The strongest immunoreactivity of selenium-binding protein 1 was seen in epithelial cells of flat cyst wall and primary papillae, followed by secondary papillae of the hierarchical structures. Micropapillae and invasive carcinoma (including microinvasion) exhibited a near complete loss of selenium-binding protein 1 expression. Selenium-binding protein 1 immunoreactivity remained the same regardless of the size of the micropapillae. Similar selenium-binding protein 1 expression was seen in the same histologic components from either ovarian serous borderline tumor or micropapillary serous borderline tumor. The gradual loss of selenium-binding protein 1 associated with increasing epithelial proliferation and papillary complexity indicates that selenium-binding protein 1 is involved in tumorigenesis of ovarian serous borderline tumor, micropapillary serous borderline tumor, and low-grade serous carcinoma. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as a possible role of selenium in chemoprevention and treatment of ovarian serous borderline tumor, micropapillary 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

References (17)

There are more references available in the full text version of this article.

Cited by (18)

  • Circulating levels of selenium-binding protein 1 (SELENBP1) are associated with risk for major adverse cardiac events and death

    2019, Journal of Trace Elements in Medicine and Biology
    Citation Excerpt :

    A 3D model has been proposed which supports Cys57 as a binding site for selenite at neutral pH [16]. SELENBP1 has been studied in tumor tissues and cell culture models, and evidence is accumulating for a dynamic regulation of intracellular SELENBP1 expression and function as a tumor suppressor [17–19]. High expression levels have been associated with reduced tumor cell proliferation or increased survival in, e.g., prostate [17] or breast cancer [20], characterizing it as a potential prognostic marker in clinical practice.

  • Selenium-binding protein 1 (SELENBP1) is a marker of mature adipocytes

    2019, Redox Biology
    Citation Excerpt :

    As several studies in tumour cells suggest that SELENBP1 counteracts proliferation and dedifferentiation [9,14,45], high SELENBP1 levels may support the maintenance of a well-differentiated phenotype in mature adipocytes.

  • Selenium Binding Protein 1: A Moonlighting Protein.

    2015, Foods and Dietary Supplements in the Prevention and Treatment of Disease in Older Adults
  • Selenium-binding protein 1: Its physiological function, dependence on aryl hydrocarbon receptors, and role in wasting syndrome by 2,3,7,8- tetrachlorodibenzo-p-dioxin

    2013, Biochimica et Biophysica Acta - General Subjects
    Citation Excerpt :

    A number of studies have suggested a tumor-suppressive role for Selenbp1. This is based on the fact that the expression of Selenbp1 is reduced in tumor tissues in the lung [6], colon [7,8], esophagus [9], ovary [10,11] and liver [12]. Conversely, elevated expression of Selenbp1 has been demonstrated in the brain of schizophrenic patients [13].

  • Evolutionary Aspects of Selenium Binding Protein (SBP)

    2023, Journal of Molecular Evolution
View all citing articles on Scopus
View full text