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Diagnosis-shift between low-grade serous ovarian cancer and serous borderline ovarian tumor: A population-based study.

ABSTRACT: OBJECTIVE:To determine changes in the characteristics of low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor (serous-BOT) in a time-specific manner. METHODS:We conducted a population-based retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Trends, demographics, and outcomes of 775 women with well-differentiated serous ovarian cancer, used as a surrogate for LGSOC, were compared to 3937 women with serous-BOT. RESULTS:In the multivariable analysis, women with LGSOC were more likely to be older, have stage II-IV disease, and have undergone hysterectomy at surgery, but less likely to be a Western U.S. resident compared to those with serous-BOT (all, adjusted-P < 0.05). During the study period, the number of LGSOCs decreased by 25.9%, particularly stage I disease (37.6% relative decrease) compared to stage II-IV disease (21.1% relative decrease) (all, P < 0.05). With a median follow-up of 16.9 years, there was a decreasing trend in the 15-year overall survival rates among LGSOC (28.7% relative decrease, P = 0.056) but not in serous-BOT (2.5% relative increase, P = 0.416) as a whole cohort. The magnitude of hazard risk from all-cause death for women with LGSOC compared to those with serous-BOT increased by 68.9% from 1988 to 2000 (P < 0.001). LGSOC remained an independent prognostic factor for decreased overall survival compared to serous-BOT (adjusted-P < 0.05). CONCLUSION:Our study suggests that the decreasing number and survival of LGSOC over time may be due to a diagnosis-shift from LGSOC to serous-BOT. Given the distinct characteristics and outcomes of LGSOC compared to serous-BOT, our study endorses the importance of making the correct diagnosis upfront. Whether this diagnostic-shift supports a hypothesis that serous-BOT is a precursor lesion of LGSOC merits further investigation.

SUBMITTER: Matsuo K

PROVIDER: S-EPMC7537352 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ovarian tumors of low malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on three normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes upregulated and 232 genes downregulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most upregulated genes in low-grade ovarian serous carcinoma. The upregulation of PAX2 was validated by real-time quantitative RT-PCR, western blot and immunohistochemical analyses. Real-time RT-PCR showed a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (P=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with earlier immunohistochemical findings, PAX2 expression was expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. In addition, the absence of PAX2 expression in normal ovarian epithelia but expression in fallopian tube fimbria and ciliated epithelial inclusions would suggest the potential development of tumors of low malignant potential and of low-grade ovarian serous carcinomas from secondary Müllerian structures.

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Diagnosis-shift between low-grade serous ovarian cancer and serous borderline ovarian tumor: A population-based study.

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