Molecular genetic alterations in endometrioid carcinomas of the ovary: Similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas

Catasús, Lluis; Bussaglia, Elena; Rodrı́guez, Ingrid; Gallardo, Alberto; Pons, Cristina; Irving, Julie; Prat, Jaime

doi:10.1016/j.humpath.2004.07.019

Cited by 166 publications

(145 citation statements)

References 40 publications

(23 reference statements)

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“…57 In addition, ovarian cancers exhibit microsatellite instability and PTEN alterations less frequently than their uterine counterparts. 13 The study of loss of heterozygosity in synchronous uterine and ovarian endometrioid tumors suggests that when is selective for one tumor site the patient is more likely to have two separate primary tumors. 58 Owing to this molecular difference, the ovarian endometrioid carcinoma grading system might not be parallel to that for uterine endometrioid carcinomas.…”

Section: Discussionmentioning

confidence: 99%

“…b-catenin gene mutations are common molecular alterations in endometrioid carcinomas and therefore have emerged as a promising prognostic marker of this tumor. [11][12][13][14][15] b-Catenin has been implicated in two important biological processes: cell-cell adhesion and signal transduction. 16 In adherens junctions of epithelial cells, b-catenin association with the cytoplasmic domain of cadherins has an important function in Ca 2 þ -dependent cell adhesion.…”

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confidence: 99%

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Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

et al. 2010

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Mutations in the b-catenin gene are common in ovarian endometrioid carcinoma. Few studies have addressed the association of b-catenin expression with tumor characteristics and patient outcome, yielding controversial results. The purpose of this study was to retrospectively assess the expression of b-catenin in ovarian endometrioid carcinoma and correlate its expression with the Gynecologic Oncology Group's (GOG) grading system, clinicopathological characteristics, and patient survival. A total of 49 patients with primary ovarian endometrioid carcinoma were included in this study. A four-tier score grading system was used for the membranous staining (negative, weak, moderate, and strong) and the percentage of positive cells for the nuclear staining of b-catenin. The status of five morphometric parameters, nuclear morphology (uniform or pleomorphic), mitotic count, glandular pattern, degree of squamous differentiation, and status of papillary pattern, was assessed. We found that a low membranous expression of b-catenin and a high mitotic count (415 per 10 high-power fields) were significantly associated with poor prognosis and early recurrence of ovarian endometrioid carcinoma. In addition, cases with nuclear expression of b-catenin showed an intermediate overall survival risk and late disease recurrence. Young age at the time of diagnosis, advanced disease stage, and suboptimal debulking were among the clinical factors predicting poor survival and early disease recurrence. The presence of squamous differentiation, a papillary pattern or nuclear pleomorphism did not show any correlation with overall survival or disease-free survival. Low membranous expression of b-catenin and high mitotic count are poor prognostic indicators in patients with ovarian endometrioid carcinoma, whereas the GOG grading system showed no prognostic value. Our data suggest that there is a need to define a better grading system for ovarian endometrioid carcinoma. Molecular markers such as b-catenin and mitotic count could aid in defining this grading system.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

et al. 2010

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“…17 Oncogenic b-catenin mutation is characteristic to the endometrioid type of ovarian carcinomas, and results in nuclear b-catenin expression. [24][25][26] We found that both high and intense MMP-7 expression in tumor cells is associated with nuclear staining of b-catenin, especially in endometrioid tumors with low stage. This is in line with other studies [24][25][26][27] and was also verified in serial sections of 10 tumors (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…[24][25][26] We found that both high and intense MMP-7 expression in tumor cells is associated with nuclear staining of b-catenin, especially in endometrioid tumors with low stage. This is in line with other studies [24][25][26][27] and was also verified in serial sections of 10 tumors (Figs. 1b and 1c, other data not shown).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of matrix metalloproteinase‐7 in epithelial ovarian cancer and its relation to β‐catenin expression

Sillanpää

Anttila

Voutilainen

et al. 2006

Intl Journal of Cancer

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We investigated the expression and prognostic significance of matrix metalloproteinase (MMP) -7, its relation to b-catenin expression and clinicopathological factors in epithelial ovarian cancer. The expression of MMP-7 was analyzed immunohistochemically in a series of 284 primary epithelial ovarian cancers, their 36 metastases and 8 normal ovaries. In cancers with endometrioid histology, a high percentage area of MMP-7 expression and an intense MMP-7 signal was significantly associated with nuclear positivity of b-catenin in cancer cells (p 5 0.003, v 2 5 8.853 and p 5 0.030, v 2 5 4.713, respectively). In all tumors and nonendometrioid subgroup, a low percentage area of MMP-7 positive tumor cells was significantly correlated with a high histological grade of the tumor (p 5 0.003 and 0.005, respectively), in all tumors also with advanced stage of the tumor (p 5 0.002) and large primary residual tumor (p 5 0.005). A 10-year disease-related survival (DRS) was significantly better when the percentage area of MMP-7 expression in cancer cells was high, when compared to low (p 5 0.0008). A high percentage area of intense MMP-7 signal in cancer cells predicted a significantly more favorable DRS and recurrence-free survival (RFS) (p 5 0.0003 and 0.0052, respectively). In multivariate analysis, a high percentage area of intense MMP-7 signal in tumor cells was an independent prognostic factor, predicting favorable DRS and RFS. The present study showed that intense MMP-7 signal in tumor cells is an independent prognostic factor predicting better survival in epithelial ovarian cancer. ' 2006 Wiley-Liss, Inc.

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“…49 Higher rates of MSI are found in endometriosis-associated cancers and in endometroid adenocarcinomas than in nonendometroid ovarian cancer. 50 Hypermethylation of both hMLH1 and PTEN with inactivation of protein expression were also demonstrated in atypical endometriosis. 51 LOH at the PTEN locus is a particularly frequent finding in clear cell carcinomas (around 30%) 52,53 and in endometrioid adenocarcinomas (approximately 60%).…”

Section: Specific Genetic Alterations In Endometriosis and Ovarian Camentioning

confidence: 98%

Ovarian endometriosis as a premalignant condition: epidemiological, histological and molecular evidence

Dreyer

2012

Southern African Journal of Gynaecological Oncology

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Endometriosis is a common monoclonal benign proliferative disorder that may give rise to pelvic malignancy. Epithelial ovarian carcinoma is responsible for a large proportion of gynaecological cancer-associated deaths. Early diagnosis is difficult and screening is generally unsuccessful. Knowledge of the risk factors for the development of endometriosis and progression to malignancy may assist in identifying women at risk of developing endometriosis-related neoplasia. The associations between infertility, endometriosis and the development of cancer are reviewed in this article. Proliferative growth, metaplasia, hyperplasia and atypia are identified as proliferative disorders in endometriosis and atypia is considered a premalignant lesion. Several endometriosis-related pelvic malignancies have been described, and these all develop from the multipotent Müllerian cell differentiating into epithelial and/or stromal components. The probable histological type depends on the site of the endometriotic lesion and the population group. Cytogenetic and specific gene alterations that are involved in the carcinogenetic process are described briefly and these may help to predict risk of malignancy or to confirm histological subtype. The importance of endometriosis as a precursor of ovarian and related malignancies was probably seriously underestimated in the past. Advances in molecular testing, histology and our understanding of oncogenesis may empower us to help prevent these devastating diseases.Peer reviewed.

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Molecular genetic alterations in endometrioid carcinomas of the ovary: Similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas

Cited by 166 publications

References 40 publications

Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

Low membranous expression of β-catenin and high mitotic count predict poor prognosis in endometrioid carcinoma of the ovary

Prognostic significance of matrix metalloproteinase‐7 in epithelial ovarian cancer and its relation to β‐catenin expression

Ovarian endometriosis as a premalignant condition: epidemiological, histological and molecular evidence

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