Elucidation of Molecular Alterations in Precursor Lesions of Ovarian Serous Carcinoma

ObjectiveA detailed understanding of the molecular alterations in different forms of cholangiocarcinogenesis is crucial for a better understanding of cholangiocarcinoma (CCA) and may pave the way to early diagnosis and better treatment options.DesignWe analysed a clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor lesions of the biliary tract and correlated the results with an independent non-IPNB/ITPN associated CCA cohort (n=294). The triplet sample set of non-neoplastic biliary epithelium, precursor and invasive CCA was analysed by next generation sequencing, DNA copy number and genome-wide methylation profiling.ResultsPatients with invasive CCA arising from IPNB/ITPN had better prognosis than patients with CCA not associated with IPNB/ITPN. ITPN was localised mostly intrahepatic, whereas IPNB was mostly of extrahepatic origin. IPNB/ITPN were equally associated with small-duct and large-duct type intrahepatic CCA. IPNB exhibited mutational profiles of extrahepatic CCA, while ITPN had significantly fewer mutations. Most mutations were shared between precursor lesions and corresponding invasive CCA but ROBO2 mutations occurred exclusively in invasive CCA and CTNNB1 mutations were mainly present in precursor lesions. In addition, IPNB and ITPN differed in their DNA methylation profiles and analyses of latent methylation components suggested that IPNB and ITPN may have different cells-of-origin.ConclusionIntegrative analysis revealed that IPNB and ITPN harbour distinct early genetic alterations, IPNB are enriched in mutations typical for extrahepatic CCA, whereas ITPN exhibited few genetic alterations and showed distinct epigenetic profiles. In conclusion, IPNB/ITPN may represent a distinctive, intermediate form of intrahepatic and extrahepatic cholangiocarcinogenesis.

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9 Role of Immunohistochemical Expression of Cyclooxygenase-2 in Ovarian Serous Carcinoma

Molecular Genetics, Gastrointestinal Carcinoma, and Ovarian Carcinoma - Handbook of Immunohistochemistry and in Situ Hybridization of Human Carcinomas ◽

10.1016/s1874-5784(05)80095-9 ◽

2005 ◽

pp. 381-385

Author(s):

Adnan R. Munkarah ◽

Rouba Ali-Fehmi

Keyword(s):

Cyclooxygenase 2 ◽

Serous Carcinoma ◽

Immunohistochemical Expression ◽

Ovarian Serous Carcinoma

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Ovarian Serous Carcinoma

Encyclopedia of Cancer ◽

10.1007/978-3-662-46875-3_6967 ◽

2017 ◽

pp. 3317-3318

Keyword(s):

Serous Carcinoma ◽

Ovarian Serous Carcinoma

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Decreased Eph receptor‑A1 expression is related to grade in ovarian serous carcinoma

Molecular Medicine Reports ◽

10.3892/mmr.2018.8528 ◽

2018 ◽

Author(s):

Yunfeng Jin ◽

Yi Zou ◽

Linling Wan ◽

Mingming Lu ◽

Ya Liu ◽

...

Keyword(s):

Serous Carcinoma ◽

Ovarian Serous Carcinoma ◽

Eph Receptor

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Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000477 ◽

2015 ◽

Vol 25 (7) ◽

pp. 1201-1207 ◽

Cited By ~ 9

Author(s):

Esther Louise Moss ◽

Tim Evans ◽

Philippa Pearmain ◽

Sarah Askew ◽

Kavita Singh ◽

...

Keyword(s):

Overall Survival ◽

Clear Cell ◽

Stage Iii ◽

Serous Carcinoma ◽

Low Grade ◽

Type I ◽

High Grade ◽

Type Ii ◽

Ovarian Serous Carcinoma ◽

Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

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