High grade serous ovarian carcinomas originate in the fallopian tube

Labidi-Galy, Sana Intidhar; Papp, Eniko; Hallberg, Dorothy; Niknafs, Noushin; Adleff, Vilmos; Noë, Michaël; Bhattacharya, Rohit; Novak, Marián; Jones, Siân; Phallen, Jillian; Hruban, Carolyn; Hirsch, Michelle S.; Lin, Douglas I.; Schwartz, Lauren E.; Maire, Cécile L.; Tille, Jean Christophe; Bowden, Michaela; Ayhan, Ayşe; Wood, Laura D.; Scharpf, Robert B.; Kurman, Robert J.; Wang, Tian Li; Shih, Ie Ming; Karchin, Rachel; Drapkin, Ronny; Velculescu, Victor E.

doi:10.1038/s41467-017-00962-1

Cited by 537 publications

(513 citation statements)

References 47 publications

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“…Furthermore, while ovarian involvement in HGSC is typically bilateral, as is common in metastasis to a paired organ, tubal involvement is unilateral in the majority of cases 12. These observations are supported by detailed molecular analysis demonstrating shared TP53 mutation between STIC and HGSC, and that the majority of mutational and copy abnormalities seen in HGSC are also identified in accompanying STIC 13. Clonal evolution studies demonstrate the same result14 15 but also show that, in advanced cases, intraepithelial tubal metastasis can produce lesions indistinguishable from STIC, further demonstrating the futility of studying advanced HGSC to answer questions about its origin.…”

Section: Resultsmentioning

confidence: 71%

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

Colombo

Sessa

Bois

et al. 2019

Int J Gynecol Cancer

323

459

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The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO–ESGO consensus conference on ovarian cancer was held on April 12–14, 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO–ESGO consensus conference, together with a summary of evidence supporting each recommendation.

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Section: Resultsmentioning

confidence: 71%

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

Colombo

Sessa

Bois

et al. 2019

Int J Gynecol Cancer

323

459

View full text Add to dashboard Cite

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“…To the best of our knowledge, this is the largest study performing whole‐exome mutational landscape analysis on p53 signatures, dormant STICs and proliferative STICs from cancer‐free women, although a recent study has also analyzed a few such lesions . We found that, compared with tubal lesions associated with ovarian cancer, these incidental tubal lesions have fewer somatic mutations or allelic imbalances, indicative of their earlier occurrence in the tumor evolution timeline.…”

Section: Discussionmentioning

confidence: 81%

Genomic landscape and evolutionary trajectories of ovarian cancer precursor lesions

Wang

Lin

et al. 2019

The Journal of Pathology

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The clonal relationship between ovarian high‐grade serous carcinoma (HGSC) and its presumed precursor lesion, serous tubal intraepithelial carcinoma (STIC), has been reported. However, when analyzing patients with concurrent ovarian carcinoma and tubal lesion, the extensive carcinoma tissues present at diagnosis may have effaced the natural habitat of precursor clone(s), obscuring tumor clonal evolutionary history, or may have disseminated to anatomically adjacent fimbriae ends, masquerading as precursor lesions. To circumvent these limitations, we analyzed the genomic landscape of incidental tubal precursor lesions including p53 signature, dormant STIC or serous tubal intraepithelial lesion (STIL) and proliferative STIC in women without ovarian carcinoma or any cancer diagnosis using whole‐exome sequencing and amplicon sequencing. In three of the four cancer‐free women with multiple discrete tubal lesions we observed non‐identical TP53 mutations between precursor lesions from the same individual. In one of the four women with co‐existing ovarian HGSC and tubal precursor lesion we found non‐identical TP53 mutations and a lack of common mutations shared between her precursor lesion and carcinoma. Analyzing the evolutionary history of multiple tubal lesions in the same four patients with concurrent ovarian carcinoma indicated distinct evolution trajectories. Collectively, the results support diverse clonal origins of tubal precursor lesions at the very early stages of tumorigenesis. Mathematical modeling based on lesion‐specific proliferation rates indicated that p53 signature and dormant STIC may take a prolonged time (two decades or more) to develop into STIC, whereas STIC may progress to carcinoma in a much shorter time (6 years). The above findings may have implications for future research aimed at prevention and early detection of ovarian cancer. Copyright © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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“…It is now believed that most serous ovarian cancers develop in the fallopian tube and can spread to the peritoneal cavity early in the course of the disease, which may make early detection more difficult 31. Therefore, the development of techniques involving brush cytology of the fallopian tube provides another potential screening avenue.…”

Section: Ca125 Screenmentioning

confidence: 99%

Ovarian cancer: screening and future directions

Gupta

Naumann

2019

Int J Gynecol Cancer

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Ovarian cancer carries a lifetime risk of approximately 2% for women and is the leading cause of death from any gynecologic malignancy. Currently, no screening program for ovarian cancer exists for the general population in the UK. This review focuses on the evidence surrounding the efficacy of current markers and discusses future improvements in screening for this disease. One-off cancer antigen 125 (CA125) measurements for detecting ovarian cancer have been well researched. However, studies have highlighted low positive predictive values (5%) and high false positive rates leading to patient anxiety and unnecessary invasive follow-up. Commonly, in the UK, CA125 is combined with transvaginal ultrasound, but there is little evidence that this approach can decrease mortality from ovarian cancer. Recently the Risk of Ovarian Cancer Algorithm, involving a combination of serial CA125 measurements and age, has been shown to detect more early stage cancers. Nevertheless, these measures are not robust in decreasing mortality from ovarian cancer and are costly to implement. Newer markers, such as human epididymis protein 4, have shown greater specificity. Its combination with CA125 and menopausal status in the Risk of Ovarian Malignancy Algorithm can predict the risk of malignancy but provides no additional benefit as a screening tool. Advanced techniques are emerging, including ultrasound molecular imaging techniques using microbubbles targeted to kinase domain receptors, and fallopian tube cytology. To reduce mortality from ovarian cancer, detection of pre-invasive lesions is imperative as ovarian cancer may develop in the fallopian tube and spread to the peritoneal cavity before being detected systemically. It seems that screening tools for ovarian cancer are currently not worthwhile for implementation into a national program. An emphasis on reducing false positives rates, associated anxiety and subsequent overdiagnosis is needed.

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High grade serous ovarian carcinomas originate in the fallopian tube

Cited by 537 publications

References 47 publications

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

Genomic landscape and evolutionary trajectories of ovarian cancer precursor lesions

Ovarian cancer: screening and future directions

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