Observer variation in histologic classification of malignant and borderline ovarian tumors

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.

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Observer Variation in Histologic Classification of Thyroid Cancer

Acta Pathologica Microbiologica Scandinavica Section A Pathology ◽

10.1111/j.1699-0463.1978.tb02073.x ◽

2009 ◽

Vol 86A (1-6) ◽

pp. 483-486 ◽

Cited By ~ 6

Author(s):

E. Saxén ◽

K. Franssila ◽

O. Bjarnason ◽

T. Normann ◽

N. Ringertz

Keyword(s):

Thyroid Cancer ◽

Observer Variation ◽

Histologic Classification

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Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profiles

International Journal of Cancer ◽

10.1002/ijc.10288 ◽

2002 ◽

Vol 98 (6) ◽

pp. 895-899 ◽

Cited By ~ 43

Author(s):

Ayodele A. Alaiya ◽

Bo Franzén ◽

Anders Hagman ◽

Bjarte Dysvik ◽

Uwe J. Roblick ◽

...

Keyword(s):

Cluster Analysis ◽

Protein Expression ◽

Hierarchical Cluster Analysis ◽

Expression Profiles ◽

Hierarchical Cluster ◽

Molecular Classification ◽

Ovarian Tumors ◽

Borderline Ovarian Tumors ◽

Protein Expression Profiles

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Management of Borderline Ovarian Tumors (BOT): results of a retrospective, single center study in Switzerland

10.1055/s-0040-1718202 ◽

2020 ◽

Author(s):

B Kipp ◽

A Vidal ◽

C Braun ◽

C Christmann

Keyword(s):

Ovarian Tumors ◽

Single Center ◽

Borderline Ovarian Tumors ◽

Single Center Study ◽

Center Study

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Assessment of lymphocyte iNKT+/CD3+/CD161+ in blood and tumor tissue in cases of benign ovarian tumors, borderline ovarian tumors and advanced-stage ovarian carcinomas

10.26226/morressier.597eedbad462b80296ca1465 ◽

2017 ◽

Author(s):

Winkler Izabela

Keyword(s):

Tumor Tissue ◽

Ovarian Tumors ◽

Advanced Stage ◽

Ovarian Carcinomas ◽

Borderline Ovarian Tumors ◽

Benign Ovarian Tumors

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Salpingo-oophorectomy versus cystectomy in patients with borderline ovarian tumors: a systemic review and meta-analysis on postoperative recurrence and fertility

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02241-2 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Peng Wang ◽

Lei Fang

Keyword(s):

Surgical Procedures ◽

Postoperative Recurrence ◽

Pregnancy Rates ◽

Ovarian Tumors ◽

Systemic Review ◽

Cochrane Library ◽

Risk Of Recurrence ◽

Borderline Ovarian Tumors ◽

Surgical Methods ◽

Meta Analyses

Abstract Background To compare the postoperative recurrence and fertility in patients with borderline ovarian tumors (BOTs) who underwent different surgical procedures: salpingo-oophorectomy versus cystectomy. Methods Potentially relevant literature from inception to Nov. 06, 2020, were retrieved in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (Pubmed). We applied the keywords “fertility-sparing surgery,” or “conservative surgery,” or “cystectomy,” or “salpingo-oophorectomy,” or “oophorectomy,” or “adnexectomy,” or “borderline ovarian tumor” for literate searching. Systemic reviews and meta-analyses were performed on the postoperative recurrence rates and pregnancy rates between patients receiving the two different surgical methods. Begger’s methods, Egger’s methods, and funnel plot were used to evaluate the publication bias. Result Among the sixteen eligible studies, the risk of recurrence was evaluated in all studies, and eight studies assessed the postoperative pregnancy rates in the BOT patients. A total of 1839 cases with borderline ovarian tumors were included, in which 697 patients (37.9%) received unilateral salpingo-oophorectomy and 1142 patients (62.1%) underwent unilateral/bilateral cystectomy. Meta-analyses showed that BOT patients with unilateral/bilateral cystectomy had significantly higher recurrence risk (OR=2.02, 95% CI: 1.59-2.57) compared with those receiving unilateral salpingo-oophorectomy. Pooled analysis of four studies further confirmed the higher risk of recurrence in patients with cystectomy (HR=2.00, 95% CI: 1.11-3.58). In addition, no significant difference in postoperative pregnancy rate was found between patients with the two different surgical procedures (OR=0.92, 95% CI: 0.60-1.42). Conclusion Compared with the unilateral/bilateral cystectomy, the unilateral salpingo-oophorectomy significantly reduces the risk of postoperative recurrence in patients with BOT, and it does not reduce the pregnancy of patients after surgery. Trial registration PROSPERO CRD42021238177

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