Abstract
Background
Borderline ovarian tumors (BOT) are uncommon but not rare epithelial ovarian neoplasms, intermediate between benign and malignant categories. Emerging knowledge supports the notion that subtypes of borderline ovarian tumors comprise distinct biologic, pathogenetic, and molecular entities, precluding a single unifying concept for BOT. Therefore, the identification of valuable markers for the diagnosis and classification of these tumors is in need. Among the molecular candidates, the Retinoblastoma (Rb) family members Rb/p105 and Rb2/p130 seem to play a pivotal role in ovarian cancer. In particular, Rb/p105, when in the unphosphorylated form, acts as a growth suppressor and plays a pivotal role in the negative control of the cell cycle and in tumor progression; whereas, the phosphorylated form (p-pRB) activates genic transcription and cellular proliferation. While Rb/p105 is ubiquitously confined to the nuclei of cycling and quiescent cells, Rb2/p130 activity is also regulated by intracellular localization. According to this premise, Rb family members could represent a novel marker in diagnosis and classification risk for patients with borderline ovarian tumors (BOT).
Aims
In this study, we evaluated the immunohistochemical expression and subcellular localization of proteins of the retinoblastoma (Rb) gene family: Rb/p105 and Rb2/p130 in 65 ovarian borderline tumors (26 serous, 19 sero-mucinous and 20 mucinous subtypes).
Results
Statistically significant differences were found in nuclear and cytoplasmic expression of Rb/p105 and Rb2/p130 according to different examined histotypes. In detail, the nuclear expression of Rb/p105 and Rb2/p130 was more frequently detected in serous (84.6%) than sero-mucinous (42.1%) and mucinous (50%) types. Conversely, the cytoplasmic expression of Rb2/p130 was not detected in serous tumors and frequently observed in mucinous subtypes (80%).
Conclusions
Our findings suggest that Rb proteins do not play a key role in the tumor progression of serous borderline tumors since they are always located in the nucleus and no cases showed a cytoplasmic localization. By contrast, the observed higher cytoplasmic expression of Rb2/p130 in mucinous BOTs (intestinal) types, is suggestive of Rb proteins involvement in the cancerogenesis pathway of mucinous ovarian tumors. Our results also suggest that mucinous BOTs of intestinal type, exhibiting low nuclear and high cytoplasmic levels of Rb2/p130 might potentially be considered a high risk category of malignant evolution. Further studies on larger series are needed in order to clarify how BOTs could be stratified in different prognostic groups according to their Rb proteins immunohistochemical profile.
Role of Retinoblastoma Protein Family (Rb/p105 and Rb2/p130) Expression in the Histopathological Classification of Borderline Ovarian Tumors
