[en] It is currently hoped that deaths from extra-uterine high-grade serous cancer (HGSC) will be reduced via opportunistic salpingectomy in healthy women. Accumulated data implicate the fimbria as a site of origin and descriptive molecular pathology and experimental evidence strongly support a serous carcinogenic sequence in the fallopian tube. Both direct and indirect ("surrogate") precursors suggest the benign tube undergoes important biologic changes after menopause, acquiring abnormalities in gene expression that are often shared with malignancy, including PAX2, ALDH1, LEF1, RCN1, RUNX2, beta catenin, EZH2 and others. However, the tube can be linked to only some HGSCs, recharging arguments that nearby peritoneum/ovarian surface epithelium (POSE) also hosts progenitors to this malignancy. A major sticking point is the difference in immunophenotype between POSE and Mullerian epithelium, essentially requiring mesothelial to Mullerian differentiation prior to or during malignant transformation to HGSC. However, emerging evidence implicates an embryonic or progenitor phenotype in the adult female genital tract with the capacity to differentiate, normally or during neoplastic transformation. Recently, a putative cell of origin to cervical cancer has been identified in the squamo-columnar (SC) junction, projecting a model whereby Krt7+ embryonic progenitors give rise to immuno-phenotypically distinct progeny under stromal influences via "top down" differentiation. Similarly, biphasic cell differentiation can be seen in the endometrium with a parallel in the juxtaposition of mesothelial and mullerian differentiation in the ovary. An abrupt mesothelial-Mullerian transition remains to be proven, but would explain the rapid evolution, short asymptomatic interval, and absence of a defined epithelial starting point in many HGSCs. Resolving this question will require accurately distinguishing progenitor from progeny tumor cells in HGSC and pinpointing where initial transformation and trans-differentiation occurs if the POSE is an origin. Both will be critical to expectations from prophylactic salpingectomy and future approaches to pelvic serous cancer prevention.
Disciplines :
Oncology
Author, co-author :
Crum, Christopher P. ✱
Herfs, Michael ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Ning, Gang ✱
Bijron, Jonathan G.
Howitt, Brooke E.
Jimenez, Cynthia A.
Hanamornroongruang, Suchanan
McKeon, Frank D.
Xian, Wa
✱ These authors have contributed equally to this work.
Language :
English
Title :
Through the glass darkly: intraepithelial neoplasia, top-down differentiation and the road to ovarian cancer.
Publication date :
2013
Journal title :
Journal of Pathology
ISSN :
0022-3417
eISSN :
1096-9896
Publisher :
John Wiley & Sons, Chichester, United Kingdom
Volume :
231
Pages :
402-412
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
This article is protected by copyright. All rights reserved.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Wigle J, Coast E, Watson-Jones D,. Human papillomavirus (HPV) vaccine implementation in low and middle-income countries (LMICs): health system experiences and prospects. Vaccine 2013; 31: 3811-3817.
Anderson GL, McIntosh M, Wu L, et al., Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study. J Natl Cancer Inst 2010; 102: 26-38.
Perez SP, Jimenez P, Olivera H, et al., Risk-reduction surgery in BRCA mutation carriers in a Spanish population: adherence and results. Clin Transl Oncol 2008; 10: 660-664.
Sigal BM, Munoz DF, Kurian AW, et al., A simulation model to predict the impact of prophylactic surgery and screening on the life expectancy of BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 2012; 21: 1066-1077.
Gilbert L, Basso O, Sampalis J, et al., Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol 2012; 13: 285-291.
Jemal A, Siegel R, Xu J, et al., Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277-300.
Coleman MP, Forman D, Bryant H, et al., Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet 2011; 377: 127-138.
Morelli M, Venturella R, Mocciaro R, et al., Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: primum non nocere. Gynecol Oncol 2013; 129: 448-451.
Piek JM, Verheijen RH, Kenemans P, et al., BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis. Gynecol Oncol 2003; 90: 491.
Medeiros F, Muto MG, Lee Y, et al., The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006; 30: 230-236.
Kindelberger DW, Lee Y, Miron A, et al., Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 2007; 31: 161-169.
Xian W, Miron A, Roh M, et al., The Li-Fraumeni syndrome (LFS): a model for the initiation of p53 signatures in the distal Fallopian tube. J Pathol 2010; 220: 17-23.
Salvador S, Rempel A, Soslow RA, et al., Chromosomal instability in Fallopian tube precursor lesions of serous carcinoma and frequent monoclonality of synchronous ovarian and Fallopian tube mucosal serous carcinoma. Gynecol Oncol 2008; 110: 408-417.
Lee Y, Miron A, Drapkin R, et al., A candidate precursor to serous carcinoma that originates in the distal Fallopian tube. J Pathol 2007; 211: 26-35.
Levanon K, Ng V, Piao HY, et al., Primary ex vivo cultures of human Fallopian tube epithelium as a model for serous ovarian carcinogenesis. Oncogene 2010; 29: 1103-1113.
Kim J, Coffey DM, Creighton CJ, et al., High-grade serous ovarian cancer arises from Fallopian tube in a mouse model. Proc Natl Acad Sci U S A 2012; 109: 3921-3926.
Pinto AP, Miron A, Yassin Y, et al., Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma. Mod Pathol 2010; 23: 404-412.
Pinto AP, Lin MC, Sheets EE, et al., Allelic imbalance in lichen sclerosus, hyperplasia, and intraepithelial neoplasia of the vulva. Gynecol Oncol 2000; 77: 171-176.
Pinto AP, Lin MC, Mutter GL, et al., Allelic loss in human papillomavirus-positive and -negative vulvar squamous cell carcinomas. Am J Pathol 1999; 154: 1009-1015.
Lin MC, Mutter GL, Trivijisilp P, et al., Patterns of allelic loss (LOH) in vulvar squamous carcinomas and adjacent noninvasive epithelia. Am J Pathol 1998; 152: 1313-1318.
Mutter GL, Lin MC, Fitzgerald JT, et al., Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000; 92: 924-930.
Levine RL, Cargile CB, Blazes MS, et al., PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma. Cancer Res 1998; 58: 3254-3258.
Mutter GL, Ince TA, Baak JP, et al., Molecular identification of latent precancers in histologically normal endometrium. Cancer Res 2001; 61: 4311-4314.
Lacey JV Jr, Mutter GL, Ronnett BM, et al., PTEN expression in endometrial biopsies as a marker of progression to endometrial carcinoma. Cancer Res 2008; 68: 6014-6020.
Baak JP, Van DB, Steinbakk A, et al., Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression. Hum Pathol 2005; 36: 555-561.
Gross AL, Kurman RJ, Vang R, et al., Precursor lesions of high-grade serous ovarian carcinoma: morphological and molecular characteristics. J Oncol 2010; 2010: 126295.
Carlson JW, Miron A, Jarboe EA, et al., Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention. J Clin Oncol 2008; 26: 4160-4165.
Jarboe E, Folkins A, Nucci MR, et al., Serous carcinogenesis in the Fallopian tube: a descriptive classification. Int J Gynecol Pathol 2008; 27: 1-9.
Esserman LJ, Thompson IM, Reid B,. Overdiagnosis and overtreatment in cancer: an opportunity for improvement. J Am Med Assoc 2013; 310: 797-798.
Ning G, Bijron JG, Yuan J, et al., Differential expression of p-ERM, a marker of cell polarity, in benign and neoplastic oviductal epithelium. Int J Gynecol Pathol 2013; 32: 345-352.
Chen EY, Mehra K, Mehrad M, et al., Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube. J Pathol 2010; 222: 110-116.
Bijron JG, Ning G, Laury AR, et al., Digital quantification of precursor frequency in the Fallopian tube and its significance. Mod Pathol 2012; 25: 1654-1661.
Quick CM, Ning G, Bijron J, et al., PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer. Mod Pathol 2012; 25: 449-455.
Crum CP, McKeon FD, Xian W,. The oviduct and ovarian cancer: causality, clinical implications, and 'targeted prevention'. Clin Obstet Gynecol 2012; 55: 24-35.
Wang X, Ouyang H, Yamamoto Y, et al., Residual embryonic cells as precursors of a Barrett's-like metaplasia. Cell 2011; 145: 1023-1035.
Xian W, Ho KY, Crum CP, et al., Cellular origin of Barrett's esophagus: controversy and therapeutic implications. Gastroenterology 2012; 142: 1424-1430.
Herfs M, Yamamoto Y, Laury A, et al., A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci U S A 2012; 109: 10516-10521.
Herfs M, Vargas SO, Yamamoto Y, et al., A novel blueprint for 'top down' differentiation defines the cervical squamocolumnar junction during development, reproductive life, and neoplasia. J Pathol 2013; 229: 460-468.
Ince TA, Cviko AP, Quade BJ, Yang A, McKeon FD, Mutter GL, Crum CP,. p63 Coordinates anogenital modeling and epithelial cell differentiation in the developing female urogenital tract. Am J Pathol 2002; 161: 1111-1117.
Xue Y, Bellanger S, Zhang W, et al., HPV16 E2 is an immediate early marker of viral infection, preceding E7 expression in precursor structures of cervical carcinoma. Cancer Res 2010; 70: 5316-5325.
Kanduc D., Translational regulation of human papillomavirus type 16 E7 mRNA by the peptide SEQIKA, shared by rabbit alpha(1)-globin and human cytokeratin 7. J Virol 2002; 76: 7040-7048.
Herfs M, Parra-Herran C, Howitt BE, Laury AR, Nucci MR, Feldman S, Jimenez CA, McKeon FD, Xian W, Crum CP,. Cervical Squamocolumnar Junction-specific Markers Define Distinct, Clinically Relevant Subsets of Low-grade Squamous Intraepithelial Lesions. Am J Surg Pathol 2013; 37: 1311-1318.
Taylor S, Wang C, Wright TC, et al., A comparison of human papillomavirus testing of clinician-collected and self-collected samples during follow-up after screen-and-treat. Int J Cancer 2011; 129: 879-886.
Younge PA,. Cancer of the uterine cervix; a preventable disease. Obstet Gynecol 1957; 10: 469-481.
Marquez RT, Baggerly KA, Patterson AP, et al., Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal Fallopian tube, endometrium, and colon. Clin Cancer Res 2005; 11: 6116-6126.
Tang S, Onuma K, Deb P, et al., Frequency of serous tubal intraepithelial carcinoma in various gynecologic malignancies: a study of 300 consecutive cases. Int J Gynecol Pathol 2012; 31: 103-110.
Carlson JW, Miron A, Jarboe EA, et al., Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention. J Clin Oncol 2008; 26: 4160-4165.
Przybycin CG, Kurman RJ, Ronnett BM, et al., Are all pelvic (nonuterine) serous carcinomas of tubal origin? Am J Surg Pathol 2010; 34: 1407-1416.
Roh MH, Kindelberger D, Crum CP,. Serous tubal intraepithelial carcinoma and the dominant ovarian mass: clues to serous tumor origin? Am J Surg Pathol 2009; 33: 376-383.
Kotsopoulos J, Terry KL, Poole EM, et al., Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin. Int J Cancer 2013; 133: 730-739.
Kurman RJ, Shih I,. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 2010; 34: 433-443.
Pothuri B, Leitao MM, Levine DA, et al., Genetic analysis of the early natural history of epithelial ovarian carcinoma. PLoS One 2010; 5: e10358.
Gusberg SB, Deligdisch L,. Ovarian dysplasia. A study of identical twins. Cancer 1984; 54: 1-4.
Hutson R, Ramsdale J, Wells M,. p53 protein expression in putative precursor lesions of epithelial ovarian cancer. Histopathology 1995; 27: 367-371.
Ferenczy A, Bertrand G, Gelfand MM,. Proliferation kinetics of human endometrium during the normal menstrual cycle. Am J Obstet Gynecol 1979; 133: 859-867.
Ferenczy A, Richart RM,. Scanning and transmission electron microscopy of the human endometrial surface epithelium. J Clin Endocrinol Metab 1973; 36: 999-1008.
Seidman JD, Khedmati F,. Exploring the histogenesis of ovarian mucinous and transitional cell (Brenner) neoplasms and their relationship with Walthard cell nests: a study of 120 tumors. Arch Pathol Lab Med 2008; 132: 1753-1760.
Mullany LK, Fan HY, Liu Z, et al., Molecular and functional characteristics of ovarian surface epithelial cells transformed by KrasG12D and loss of Pten in a mouse model in vivo. Oncogene 2011; 30: 3522-3536.
Deligdisch L, Gil J, Kerner H, et al., Ovarian dysplasia in prophylactic oophorectomy specimens: cytogenetic and morphometric correlations. Cancer 1999; 86: 1544-1550.
Auersperg N., Ovarian surface epithelium as a source of ovarian cancers: unwarranted speculation or evidence-based hypothesis? Gynecol Oncol 2013; 130: 246-251.
Garrett LA, Vargas SO, Drapkin R, et al., Does the fimbria have an embryologic origin distinct from that of the rest of the Fallopian tube? Fertil Steril 2008; 90: 2008.
Flesken-Nikitin A, Hwang CI, Cheng CY, et al., Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature 2013; 495: 241-245.
Sasaki R, Narisawa-Saito M, Yugawa T, et al., Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes. Carcinogenesis 2009; 30: 423-431.
Ong A, Maines-Bandiera SL, Roskelley CD, et al., An ovarian adenocarcinoma line derived from SV40/E-cadherin-transfected normal human ovarian surface epithelium. Int J Cancer 2000; 85: 430-437.
King SM, Quartuccio SM, Vanderhyden BC, et al., Early transformative changes in normal ovarian surface epithelium induced by oxidative stress require Akt upregulation, DNA damage and epithelial-stromal interaction. Carcinogenesis 2013; 34: 1125-1133.
Barakat RR, Federici MG, Saigo PE, et al., Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes. Cancer 2000; 89: 383-390.
Folkins AK, Jarboe EA, Saleemuddin A, et al., A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and Fallopian tubes from women with BRCA mutations. Gynecol Oncol 2008; 109: 168-173.
Cai KQ, Wu H, Klein-Szanto AJ, et al., Acquisition of a second mutation of the Tp53 alleles immediately precedes epithelial morphological transformation in ovarian tumorigenicity. Gynecol Oncol 2009; 114: 18-25.
Gardi NL, Deshpande T, Kamble S, Budhe S, Bapat SA,. Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases. Clin Cancer Res 2013 Oct 16.
Powell CB, Swisher EM, Cass I, McLennan J, Norquist B, Garcia RL, Lester J, Karlan BY, Chen L,. Long term follow up of BRCA1 and BRCA2 mutation carriers with unsuspected neoplasia identified at risk reducing salpingo-oophorectomy. Gynecol Oncol 2013; 129: 364-371.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
