Serous tubal intraepithelial carcinomas associated with high‐grade serous ovarian carcinomas: a systematic review

Chen, F; Gaitskell, Kezia; García, Maria José; Albukhari, Ashwag; Tsaltas, Jim; Ahmed, Ashfaq

doi:10.1111/1471-0528.14543

Cited by 63 publications

(51 citation statements)

References 37 publications

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“…Larger studies will be required to test these hypotheses. Epithelial cell dynamics in the fallopian tube have not been extensively studied, but in the last two decades, interest in this organ has been piqued by strong evidence to support a fallopian tube origin for the majority of high-grade serous 'ovarian' carcinomas (Callahan et al, 2007;Chen et al, 2017;Lee et al, 2007;Medeiros et al, 2006;Meserve et al, 2017). The pseudostratified epithelium of the fallopian tube consists of two major cellular populations.…”

Section: Discussionmentioning

confidence: 99%

“…The pseudostratified epithelium of the fallopian tube consists of two major cellular populations. A secretory population that expresses the PAX8 transcription factor is thought to be the predominant cell-of-origin for HGSC (Callahan et al, 2007;Chen et al, 2017;Ducie et al, 2017;Lawrenson et al, 2019;Lee et al, 2007;Medeiros et al, 2006;Meserve et al, 2017). Fallopian secretory epithelia are more proliferative in vitro and in vivo and less competent at repairing DNA damage compared to the FOXJ1-positive ciliated population (Levanon et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube

Dinh

Lin

Abbasi

et al. 2020

Preprint

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The human fallopian tube harbors the cell-of-origin for the majority of high-grade serous 'ovarian' cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We performed single-cell transcriptomic profiling in 12 primary fallopian specimens from 8 patients, analyzing around 53,000 individual cells to map the major immune, fibroblastic and epithelial cell types present in this organ. We identified 10 epithelial sub-populations, characterized by diverse transcriptional programs including SOX17 (enriched in secretory epithelial cells), TTF3 and RFX3 (enriched in ciliated cells) and NR2F2 (enriched in early, partially differentiated secretory cells). Based on transcriptional signatures, we reconstructed a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3 high intermediate. Computational deconvolution of the cellular composition of advanced HGSCs based on epithelial subset signatures identified the 'early secretory' population as a likely precursor state for the majority of HGSCs. The signature of this rare population of cells comprised both epithelial (EPCAM, KRT) and mesenchymal (THY1, ACTA2) features, and was enriched in mesenchymal-type HGSCs (P = 6.7 x 10 -27 ), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube

Dinh

Lin

Abbasi

et al. 2020

Preprint

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“…The epithelium of STIC showed strong p53 positivity and harbors clonal TP53 mutations (12). It has been suggested that STIC is found in 11-68% of HGSC patients (12,20,21) as well as up to 60% of sporadic cancer cases and in 0.6-10% of the carriers of patients with hereditary cancer (22). Conversely, the frequency of fallopian tube precursors in benign gynecologic diseases was approximately 20% of SCOUT, 10% of p53 signature and <4% of STIC cases (1,2).…”

Section: Histopathology Of Precursor Lesionsmentioning

confidence: 99%

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

et al. 2017

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Abstract. The present review focuses on the current status of molecular pathology in high-grade serous cancer (HGSC) and preneoplastic conditions. This article reviews the English-language literature on HGSC, precursor, fallopian tubal epithelium, secretory cells, ciliated cells, secretory cell expansion, secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC), DNA damage and immunohistochemistry in an effort to identify the precursor-carcinoma sequence in HGSC. The majority of HGSC originates from the fimbriated end of the fallopian tube secretory epithelial cells, while the small part of this disease may develop from ovarian cortical inclusion cyst (CIC). A series of morphological changes from normal fallopian epithelium to preneoplastic to neoplastic lesions were concomitant with the multistep accumulation of molecular and genetic alterations. Recent studies provide a stepwise progression of fallopian tubal epithelium to precursor lesions to carcinoma, with the aid of a 'secretory cell-SCE-SCOUT-p53 signature-STIC-HGSC sequence' model. Immunohistochemical markers, including p53, STMN1, EZH2, CCNE1, Ki67 and γ-H2AX, were gradua lly increased during the SCOUT-p53 signature-STIC-HGSC sequence. Conversely, PAX2 expression was decreased during the early phase of SCOUT development. Potential genes and proteins are involved in the evolutionary trajectory of the precursor-cancer lineage model. In the present review we examined detailed aspects of the molecular changes involved in malignant transformation from fallopian tube epithelium to HGSC. A precursor condition originating in 'field cancerization' may gain a growth advantage, leading to HGSC.

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“…Based on multiple studies, the frequency of an intramucosal carcinoma in the fallopian tube of the patient with a symptomatic HGSC ranged from as low as 10% to as high as 60%. 18 Either estimate left a large percentage of HGSC in which a clear-cut early malignancy in the fallopian tube could not be identified. Proponents of other potential sources pointed to the ovarian surface epithelium or the secondary Mullerian system.…”

Section: Unanswered Questionsmentioning

confidence: 99%

Back to the Future? The Fallopian Tube, Precursor Escape and a Dualistic Model of High-Grade Serous Carcinogenesis

Soong¹,

Kolin²,

Teschan³

et al. 2018

Preprint

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Beginning with the discovery of the BRCA ovarian cancer susceptibility genes and subsequent detailed examination of risk reduction salpingo-oophorectomy (RRSO) specimens, a new paradigm of ovarian carcinogenesis has unfolded with attention to the distal fallopian tube. The primary focus has been an early cancer in the fallopian tube which is seen in virtually all incidentally discovered high-grade serous cancers in asymptomatic women. This high-frequency of tubal involvement in early serous cancer - serous tubal intraepithelial carcinoma or STIC - has galvanized attention to this organ as a primary source of this disease. However, an enduring mystery has been the relatively low frequency of STIC in fallopian tubes of women with advanced malignancy. This paradox, a high-frequency of tubal involvement early and a low-frequency late in the disease process has spurred interest in other potential sources, such as the ovarian surface or secondary Mullerian system. However, because essentially all high-grade serous carcinomas are linked by TP53 mutations, and because fallopian tubes frequently contain early serous proliferations (ESPs) with these mutations, attention has turned to the possibility that nonmalignant but TP53 mutated tubal epithelium could be responsible for an eventual malignancy. Recent data have shown evidence of lineage continuity between ESPs and concurrent serous carcinomas prompting the concept of "precursor escape". This creates a 2nd component of the paradigm by which cells from early lesions can escape the fallopian tube and undergo future malignant transformation later, emerging suddenly as widespread malignancy. This dualistic model thus explains the paradox and opens new questions pertaining to the challenge of both early detection and prevention of this lethal malignancy.

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Serous tubal intraepithelial carcinomas associated with high‐grade serous ovarian carcinomas: a systematic review

Abstract: A systematic review of the incidence of STICs in HGSOCs identifies significant methodological inconsistencies.

Cited by 63 publications

References 37 publications

Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube

Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

Back to the Future? The Fallopian Tube, Precursor Escape and a Dualistic Model of High-Grade Serous Carcinogenesis

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