The Value of Cell Proliferation and Angiogenesis in the Prognostic Assessment of Ovarian Granulosa cell Tumors

Jurić, Gordana; Žarković, Neven; Nola, Marin; Tillian, Manfred; Jukić, Silvana

doi:10.1177/030089160108700111

Cited by 34 publications

(29 citation statements)

References 28 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous data suggest that mitotic index is a prognostic marker in GCTs (41)(42)(43), but this has not been found in all studies (22,40). We found that VEGF protein expression correlated positively to tumor MVD, independent of tumor size or stage.…”

Section: Discussioncontrasting

confidence: 79%

See 1 more Smart Citation

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Färkkilä¹,

Anttonen²,

Pociuviene³

et al. 2011

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Ovarian granulosa cell tumors (GCTs) are hormonally active sex cord stromal tumors accounting for 3-5% of all ovarian cancers. These tumors are generally diagnosed at an early stage but there is a high risk of recurrence, associated with high mortality. Treatment of recurrent GCTs is difficult, and biologically targeted treatment modalities are lacking. GCTs are highly vascularized, and angiogenic factors most probably play a role in their pathology. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, but in GCTs, the role of VEGF and its receptors VEGFR-1 (FLT1) and VEGFR-2 (KDR) remains largely unknown. Our objective is to study the expression of VEGF and its receptors in human GCTs. Methods: We analyzed GCTs from 106 patients for the expressions of VEGF and its receptors utilizing tumor tissue microarray, tumor mRNA, and patient serum samples. Results: We found that VEGF and its main biologically active receptor VEGFR-2 were highly expressed in primary and recurrent GCTs, when compared with normal granulosa-lutein cells. The expression of VEGF correlated positively to tumor microvessel density and to VEGFR-2 expression at the protein (P!0.05) and mRNA (P!0.05) levels. In contrast to VEGFR-2, the expression of VEGFR-1 was weak. Tumor VEGF protein expression was not prognostic for recurrence, however, we found high levels of circulating VEGF in the serum of patients with primary GCT. Conclusions:The results suggest an important role of VEGF and VEGFR-2 in GCT pathology and support the possibility of applying novel VEGF-or VEGFR-2-targeted treatments to patients with GCT.

show abstract

Section: Discussioncontrasting

confidence: 79%

“…As an indirect indicator of tumor angiogenesis, MVD has been shown to be of prognostic significance in ovarian cancer (39), but its role in GCTs is still unknown (40). Previous data suggest that mitotic index is a prognostic marker in GCTs (41)(42)(43), but this has not been found in all studies (22,40).…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Färkkilä¹,

Anttonen²,

Pociuviene³

et al. 2011

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…In other, more benign tumors, no correlation of proliferation and angiogenesis has been reported [12,13] . In paragangliomas, a benign tumor entity with some malignant characteristics, only limited data concerning angiogenesis and proliferation are available.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Expression, Vascularization and Proliferation in Paragangliomas

Brieger¹,

Bedavanija

Gosepath³

et al. 2005

ORL

View full text Add to dashboard Cite

Objective/Hypothesis: Paragangliomas are heavily vascularized tumors, and the expression of VEGF (vascular endothelial growth factor) has been reported. The aim of our study was to extend the available database of VEGF expression in paraganglioma, to add correlated data concerning vessel density and proliferative activity, and to draw conclusions concerning the mechanisms resulting in tumor vascularization and growth. Study Design: Semiquantitative histopathologic examination of paraganglioma specimens obtained from surgical cases. Methods: Paraffin-embedded paragangliomas were analyzed by immunohistochemistry. Fourteen consecutive samples were hybridized with VEGF-, CD31- and Ki67-specific antibodies, and visualized by diaminobenzidine staining. Vessel density was determined by counting CD31-positive vessels and proliferation by quantification of Ki67-positive cells. Results: Ten out of 14 samples were positive for VEGF. In this group, vessel density was up to 5 times as high and proliferative activity was about twice as high as in the VEGF-negative group. Conclusions: We observed higher CD31 and Ki67 counts in VEGF-positive tumors, but statistical significance could not be assessed due to low sample numbers. These data might suggest a contribution of VEGF secreted by paragangliomas to tumor vascularization and possibly proliferation. The clinical impact of VEGF expression analysis has to be proven in future studies.

show abstract

“…50,51 An association between the mitotic activity index (MI) of granulosa cell tumor and survival or recurrence has been reported in several studies. 10,12,14,15,55,58,61 In one of these studies, patients whose tumors had a low MI (<3 MI per 10 high-power fields [HPFs]) had a 10-year survival of 70% compared with 37% for those whose tumors had higher MI. 15 In a series, 53 tumors that had <4 mitoses/10 HPFs had a more than 2 times risk of recurrence than did those with <3 mitoses/10 HPFs.…”

Section: Prognostic Factorsmentioning

confidence: 99%

“…In contrast, other investigators were unable to show that nuclear atypia was of any prognostic significance. 48,61 DNA analyses have indicated that 5% to 20% of granulosa cell tumors are aneuploid. According to some investigators aneuploidy was not a predictor for recurrence, 58,[62][63][64] whereas others found that aneuploidy was associated with high risk for recurrence.…”

Section: Prognostic Factorsmentioning

confidence: 99%

Granulosa Cell Tumor of the Ovary: Tumor Review

et al. 2008

View full text Add to dashboard Cite

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis.

show abstract

The Value of Cell Proliferation and Angiogenesis in the Prognostic Assessment of Ovarian Granulosa cell Tumors

Cited by 34 publications

References 28 publications

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

Vascular Endothelial Growth Factor Expression, Vascularization and Proliferation in Paragangliomas

Granulosa Cell Tumor of the Ovary: Tumor Review

Contact Info

Product

Resources

About