Changes in the Extracellular Matrix Are Associated With the Development of Serous Tubal Intraepithelial Carcinoma Into High-Grade Serous Carcinoma

2017 ◽  
Vol 27 (6) ◽  
pp. 1072-1081 ◽  
Author(s):  
Sophieke C.H.A. van der Steen ◽  
Johan Bulten ◽  
Koen K. Van de Vijver ◽  
Toin H. van Kuppevelt ◽  
Leon F.A.G. Massuger
Keyword(s):  
Extracellular Matrix ◽  
Cancer Progression ◽  
Serous Carcinoma ◽  
High Grade ◽  
Full Spectrum ◽  
Preinvasive Lesions ◽  
Intraepithelial Carcinoma ◽  
Screening And Prevention ◽  
Step Transition ◽  
Intraepithelial Lesions

ObjectiveThe identification of a marker for early progression of preinvasive lesions into invasive pelvic high-grade serous carcinoma (HGSC) may provide novel handles for innovative screening and prevention strategies. The interplay between cancer cells and the extracellular matrix (ECM) is one of the main principles in cancer development and growth, but has been largely neglected in preinvasive lesions. This is the first study addressing the involvement of the ECM in the “step-by-step” transition of normal fallopian tube epithelium into preinvasive lesions, and eventually the progression of preinvasive lesions into invasive HGSC.MethodsThe expression of highly sulfated chondroitin sulfate (CS-E), a characteristic glycosaminoglycan of the cancer-associated ECM, was assessed by immunohistochemistry in a large cohort of precursor lesions of the full spectrum of HGSC development, including 97 serous tubal intraepithelial carcinomas (STICs), 27 serous tubal intraepithelial lesions, and 24 p53 signatures. In addition, the immunological reactivity in the microenvironment was evaluated.ResultsIncreased stromal expression of highly sulfated CS-E was observed in 3.7%, 57.7%, and 90.6% of serous tubal intraepithelial lesions, STICs, and invasive HGSCs, respectively (P < 0.001). No or limited expression was found in p53 signatures and normal tubal epithelium (compared with STIC, P < 0.001). A gradual increase in the amount of CS-E expression between STIC and paired HGSC was demonstrated. Intense stromal CS-E expression in STIC was significantly associated with an immune infiltrate (P < 0.001).ConclusionsOur study showed that increased stromal CS-E expression is related to the degree of the tubal epithelium abnormality. Specific alterations in the ECM (ie, CS-E expression) occur early in pelvic HGSC development and may represent a novel biomarker of early cancer progression, useful for the identification of novel clinical strategies.

scholarly journals Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis—Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 120 ◽  
Author(s):  
Isao Otsuka ◽  
Takuto Matsuura
Keyword(s):  
Fallopian Tube ◽  
Ovarian Surface Epithelium ◽  
Serous Carcinoma ◽  
Ca 125 ◽  
Surface Epithelium ◽  
Screening Methods ◽  
High Grade ◽  
Endometrial Cavity ◽  
Screening And Prevention ◽  
Tumor Dna

High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian carcinoma. Many HGSCs are now believed to originate in the fallopian tube epithelium; ovarian surface epithelium is another possible origin. Thus, current screening methods, i.e., ultrasonography and serum CA-125 measurements, have a limitation in their early detection. Recently, circulating biomarkers, such as tumor DNA, autoantibody, and microRNA, have been investigated to detect HGSCs. As cancer cells in the fallopian tube flow into the endometrial cavity, the detection of exfoliated cells, tumor DNA, and proteome from samples obtained from the endometrial cavity or the cervix may be useful. The risk of ovarian serous carcinoma is affected by the use of oral contraceptive and menopausal hormone therapy (MHT). MHT regimens causing endometrial bleeding increase serous carcinoma risk, hence, incessant retrograde bleeding from the endometrial cavity into the Douglas pouch appears to play an important role in high-grade serous carcinogenesis. In this review, we provide an overview of current and novel screening methods and prevention approaches for ovarian and fallopian tube HGSC.

scholarly journals Preneoplastic lesions fimbria pan-proteomic studies establish the fimbriectomy benefit for BRCA1/2 patients and identify early diagnosis markers of HGSC

2020 ◽  
Author(s):  
Maxence Wisztorski ◽  
Philippe Saudemont ◽  
Soulaimane Aboulouard ◽  
Tristan Cardon ◽  
Fabrice Narducci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Cancer ◽  
Specific Protein ◽  
Serous Carcinoma ◽  
Preneoplastic Lesions ◽  
Spatially Resolved ◽  
Intraepithelial Carcinoma ◽  
Cancer Phenotypes ◽  
Epithelial Lesions ◽  
Intraepithelial Lesions

ABSTRACTOvarian cancer is the leading cause of death from gynecologic cancer worldwide; however, the origin of ovarian tumors, particularly for high-grade serous carcinoma (HGSC), is still debated. Accumulated evidence converges towards the involvement of the preneoplastic lesions observed in the fimbriated end of the fallopian tubes. In this study, we propose to carry out an in-depth proteomics analysis of these epithelial lesions (p53 signature, serous tubal intraepithelial carcinoma-STIC and serous tubal intraepithelial lesions-STIL) based on spatially resolved proteomic guided by IHC technique. We identified specific clusters related to each preneoplastic lesions, specific protein mutations based on Cosmic database and a Ghost proteome translated from non-coding RNAs and alternative ORFs, using the OpenProt database. Protein networks have been constructed from each cluster utilizing systems biology platform. Generated data were used to confirm the potentially dormant character of the STIL lesion and the more aggressive profile of the STIC which appears closer to HGSC than other lesions. In summary, our results established the chronological mechanisms and genesis of different ovarian cancer phenotypes but also identified the early diagnostic markers of HCSC guiding an adapted therapy and a better patient care.

scholarly journals Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Amy L. Gross ◽  
Robert J. Kurman ◽  
Russell Vang ◽  
Ie-Ming Shih ◽  
Kala Visvanathan
Keyword(s):  
Fallopian Tube ◽  
Screening Tools ◽  
Serous Carcinoma ◽  
Molecular Characteristics ◽  
High Grade ◽  
Precursor Lesions ◽  
Serous Ovarian Carcinoma ◽  
Brca 1 ◽  
Putative Precursor ◽  
Intraepithelial Lesions

The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC), particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs) but our own findings (unpublished data) and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs).

Ovarian Carcinosarcoma and Concurrent Serous Tubal Intraepithelial Carcinoma With Next-Generation Sequencing Suggesting an Origin From the Fallopian Tube

2019 ◽  
Vol 27 (5) ◽  
pp. 574-579 ◽  
Author(s):  
Sharlene Helene C. See ◽  
Amir Behdad ◽  
Kruti P. Maniar ◽  
Luis Z. Blanco
Keyword(s):  
Next Generation Sequencing ◽  
Fallopian Tube ◽  
Tp53 Gene ◽  
Serous Carcinoma ◽  
High Grade ◽  
Next Generation ◽  
Serous Tubal Intraepithelial Carcinoma ◽  
Divergent Differentiation ◽  
Intraepithelial Carcinoma ◽  
Generation Sequencing

Background. Ovarian carcinosarcomas are rare aggressive biphasic tumors. Evidence suggests that these tumors are monoclonal and that the sarcoma component is derived from a stem cell undergoing divergent differentiation. Currently, there remains a paucity of data regarding its origin, with few reports suggesting an association with serous tubal intraepithelial carcinoma (STIC) by immunohistochemistry and genetics. Objective. We sought to determine the relationship of carcinosarcoma to high-grade serous carcinoma and STIC by investigating for similar mutation signatures through next-generation sequencing. Methodology. A case of carcinosarcoma with associated high-grade serous carcinoma and STIC was macrodissected, and next-generation sequencing was performed on each component separately. Results. The STIC, high-grade serous carcinoma component, and chondrosarcoma component were all diffusely positive for p53 and p16 by immunohistochemistry. Next-generation sequencing demonstrated an identical TP53 gene c.376-1G>A 5’ splice site pathogenic mutation in all 3 components. Conclusions. Our findings suggest that carcinosarcomas may also originate from the fallopian tube.

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