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Mucinous borderline ovarian tumor versus invasive well-differentiated mucinous ovarian cancer: Difference in characteristics and outcomes.

ABSTRACT: OBJECTIVE:Mucinous borderline ovarian tumor (mucinous-BOT) and invasive well-differentiated mucinous ovarian cancer (mucinous-OC) are often histopathologically misclassified. The objective of this study was to examine differences in clinico-pathological characteristics and outcomes of these two entities. METHODS:This is a retrospective population-based study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Stage I mucinous-BOTs and stage I well-differentiated mucinous-OC were compared for patient demographics, tumor characteristics, and outcomes. Propensity score matching and multivariable analysis were used to assess cause-specific survival (CSS). RESULTS:A total of 2130 mucinous-BOT and 581 mucinous-OC cases were examined for analysis. On multivariable analysis, women with mucinous-OC were more likely to be older, Eastern U.S. residents, and have undergone hysterectomy or lymphadenectomy compared to those with mucinous-BOT, and the number of women diagnosed with mucinous-OC decreased over time (all, P?

SUBMITTER: Matsuo K

PROVIDER: S-EPMC7523227 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Mucinous borderline ovarian tumor versus invasive well-differentiated mucinous ovarian cancer: Difference in characteristics and outcomes.

Matsuo Koji K Machida Hiroko H Mandelbaum Rachel S RS Grubbs Brendan H BH Roman Lynda D LD Sood Anil K AK Gershenson David M DM

Gynecologic oncology 20190220 2

<h4>Objective</h4>Mucinous borderline ovarian tumor (mucinous-BOT) and invasive well-differentiated mucinous ovarian cancer (mucinous-OC) are often histopathologically misclassified. The objective of this study was to examine differences in clinico-pathological characteristics and outcomes of these two entities.<h4>Methods</h4>This is a retrospective population-based study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Stage I mucinous-BOTs and stage I well- ...[more]

PMID: 30797590

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Project description:BackgroundDue to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking.MethodsThe New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry.ResultsFrom the New England Case-Control study, 287 cases of MON were compared against 2339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83-1.92, p = 0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48-2.80, p < 0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas.ConclusionPrior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases.FundingNational Cancer Institute grants P50-CA105009 and R21 CA-156021; The Honorable Tina Brozman 'Tina's Wish' Foundation; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Dana-Farber Cancer Institute - Susan Smith Center for Women's Cancers; Robert and Deborah First Fund; The Gamel Family Fund; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Arthur Sachs/Fulbright/Harvard; La Fondation Philippe; La Fondation de France.

Project description:Epithelial ovarian cancer (EOC) are a heterogeneous collection of malignancies, each with their own developmental origins, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis with a 5-year survival of 11% for advanced stages (III/IV). Clinically, due to the large size and heterogeneity of mu-cinous tumors, Malignant forms are difficult to distinguish from Borderline (15%) and benign (80%) forms with a better prognosis. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, miRNA expres-sion profiling generates using FFPE patient samples followed by qRT-PCR validation allows to identify 10 down-regulated and 5 up-regulated miRNAs between Malignant and Borderline tumors. To overcome issues linked to data normalization and to improve the accuracy of the results, a ratio analysis combining up-regulated and down-regulated miRNAs was used. Alt-hough 21/50 miRNA expression ratio were significantly different between Malignant and Bor-derline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 miRNAs expression ratio (double ratio) showed high discriminatory poten-tial, with 100% of accuracy in distinguishing Malignant and Borderline ovarian tumors, and suggests that miRNAs may hold significant clinical potential as a diagnostic tool. Epithelial ovarian cancer (EOC) are a heterogeneous collection of malignancies, each with their own developmental origins, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis with a 5-year survival of 11% for advanced stages (III/IV). Clinically, due to the large size and heterogeneity of mu-cinous tumors, Malignant forms are difficult to distinguish from Borderline (15%) and benign (80%) forms with a better prognosis. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, miRNA expres-sion profiling generates using FFPE patient samples followed by qRT-PCR validation allows to identify 10 down-regulated and 5 up-regulated miRNAs between Malignant and Borderline tumors. To overcome issues linked to data normalization and to improve the accuracy of the results, a ratio analysis combining up-regulated and down-regulated miRNAs was used. Alt-hough 21/50 miRNA expression ratio were significantly different between Malignant and Bor-derline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 miRNAs expression ratio (double ratio) showed high discriminatory poten-tial, with 100% of accuracy in distinguishing Malignant and Borderline ovarian tumors, and suggests that miRNAs may hold significant clinical potential as a diagnostic tool.

Project description:IntroductionRecent classification of neuroendocrine neoplasms has defined well-differentiated high-grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well-described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens.Materials and methodsThis was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients' demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression-free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR).ResultsTreatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki-67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum-etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96-16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months.ConclusionAmong patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short-lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy.Implications for practiceHigh-grade well-differentiated neuroendocrine tumors (NET G3) are considered a different entity from low-grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well-differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.

Dataset Information

Mucinous borderline ovarian tumor versus invasive well-differentiated mucinous ovarian cancer: Difference in characteristics and outcomes.

Publications

Mucinous borderline ovarian tumor versus invasive well-differentiated mucinous ovarian cancer: Difference in characteristics and outcomes.

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