Epithelial ovarian cancer: Difference between revisions

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==== The origin of epithelial ovarian tumors from fallopian tubes and endometrium, and not from ovaries ====
* The evidence from recent studies indicate that majority of epithelial ovarian cancers have their origin outside ovaries, especially from fallopian tubes and endometrium. This idea is supported by several observations in a number of studies.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref>
* The histology of serous, endometrioid and clear cell carcinoma demonstrates that their morphology is similar to that fallopian tubes, and endometrium rather than ovarian epithelium.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid19342944">{{cite journal |vauthors=Veras E, Mao TL, Ayhan A, Ueda S, Lai H, Hayran M, Shih IeM, Kurman RJ |title=Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases |journal=Am. J. Surg. Pathol. |volume=33 |issue=6 |pages=844–53 |date=June 2009 |pmid=19342944 |doi=10.1097/PAS.0b013e31819c4271 |url=}}</ref><ref name="pmid9383841">{{cite journal |vauthors=Martin DC |title=Cancer and endometriosis: do we need to be concerned? |journal=Semin. Reprod. Endocrinol. |volume=15 |issue=3 |pages=319–24 |date=1997 |pmid=9383841 |doi=10.1055/s-2008-1068762 |url=}}</ref>
* Presence of PAX8, a Müllerian marker, and absence of calretinin, a mestothelial marker, further supports the theory. Moreover the genetic profile expression similarities and presence of similar TP53 mutation signatures in serous tubal intra-epithelial tumors and epithelial ovarian cancers also supports the extra-ovarian origin of epithelial ovarian cancer.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid17255760">{{cite journal |vauthors=Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP |title=Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship |journal=Am. J. Surg. Pathol. |volume=31 |issue=2 |pages=161–9 |date=February 2007 |pmid=17255760 |doi=10.1097/01.pas.0000213335.40358.47 |url=}}</ref><ref name="pmid16144910">{{cite journal |vauthors=Marquez RT, Baggerly KA, Patterson AP, Liu J, Broaddus R, Frumovitz M, Atkinson EN, Smith DI, Hartmann L, Fishman D, Berchuck A, Whitaker R, Gershenson DM, Mills GB, Bast RC, Lu KH |title=Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon |journal=Clin. Cancer Res. |volume=11 |issue=17 |pages=6116–26 |date=September 2005 |pmid=16144910 |doi=10.1158/1078-0432.CCR-04-2509 |url=}}</ref>.<ref
* In cases when fallopian tubes were removed carefully along with ovarian and/or peritoneal serous cancer, the involvement of mucosa of the tubes were found to be involved in about 70% of the cases.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref>
* In 2001, a Dutch study revealed the presence of high grade serous carcinomas in fallopian tubes of women with genetic susceptibility to hereditary ovarian cancers with no evidence of such lesions in ovaries of same women. These lesions were termed as serous tubal intra-epithelial tumors.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid17255760">{{cite journal |vauthors=Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP |title=Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship |journal=Am. J. Surg. Pathol. |volume=31 |issue=2 |pages=161–9 |date=February 2007 |pmid=17255760 |doi=10.1097/01.pas.0000213335.40358.47 |url=}}</ref><ref name="pmid11745677">{{cite journal |vauthors=Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, Gille JJ, Jongsma AP, Pals G, Kenemans P, Verheijen RH |title=Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer |journal=J. Pathol. |volume=195 |issue=4 |pages=451–6 |date=November 2001 |pmid=11745677 |doi=10.1002/path.1000 |url=}}</ref><ref name="pmid17761984">{{cite journal |vauthors=Callahan MJ, Crum CP, Medeiros F, Kindelberger DW, Elvin JA, Garber JE, Feltmate CM, Berkowitz RS, Muto MG |title=Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction |journal=J. Clin. Oncol. |volume=25 |issue=25 |pages=3985–90 |date=September 2007 |pmid=17761984 |doi=10.1200/JCO.2007.12.2622 |url=}}</ref>
* Additional studies demonstrated the presence of similar lesions in fallopian tubes of women without genetic susceptibility to ovarian cancer. In cases when fallopian tubes were removed carefully along with ovarian and/or peritoneal serous cancer, the involvement of mucosa of the tubes were found to be involved in about 70% of the cases.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid17255760">{{cite journal |vauthors=Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP |title=Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship |journal=Am. J. Surg. Pathol. |volume=31 |issue=2 |pages=161–9 |date=February 2007 |pmid=17255760 |doi=10.1097/01.pas.0000213335.40358.47 |url=}}</ref><ref name="pmid11745677">{{cite journal |vauthors=Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, Gille JJ, Jongsma AP, Pals G, Kenemans P, Verheijen RH |title=Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer |journal=J. Pathol. |volume=195 |issue=4 |pages=451–6 |date=November 2001 |pmid=11745677 |doi=10.1002/path.1000 |url=}}</ref><ref name="pmid17761984">{{cite journal |vauthors=Callahan MJ, Crum CP, Medeiros F, Kindelberger DW, Elvin JA, Garber JE, Feltmate CM, Berkowitz RS, Muto MG |title=Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction |journal=J. Clin. Oncol. |volume=25 |issue=25 |pages=3985–90 |date=September 2007 |pmid=17761984 |doi=10.1200/JCO.2007.12.2622 |url=}}</ref>
* These tubal serous lesions were located in fimbria in almost all of the cases, giving rise to the proposition that serous tumors originated in fallopian tubes and then implantation into ovaries.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid12893227">{{cite journal |vauthors=Piek JM, Verheijen RH, Kenemans P, Massuger LF, Bulten H, van Diest PJ |title=BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis |journal=Gynecol. Oncol. |volume=90 |issue=2 |pages=491 |date=August 2003 |pmid=12893227 |doi= |url=}}</ref><ref name="pmid17255760">{{cite journal |vauthors=Kindelberger DW, Lee Y, Miron A, Hirsch MS, Feltmate C, Medeiros F, Callahan MJ, Garner EO, Gordon RW, Birch C, Berkowitz RS, Muto MG, Crum CP |title=Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship |journal=Am. J. Surg. Pathol. |volume=31 |issue=2 |pages=161–9 |date=February 2007 |pmid=17255760 |doi=10.1097/01.pas.0000213335.40358.47 |url=}}</ref><ref name="pmid16434898">{{cite journal |vauthors=Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP |title=The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome |journal=Am. J. Surg. Pathol. |volume=30 |issue=2 |pages=230–6 |date=February 2006 |pmid=16434898 |doi= |url=}}</ref>
* The association between adnexal malignant mixed mesodermal tumors and serous tubal intraepithelial tumors pints further in direction of tubal origin of these epithelial ovarian tumors.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid24328014">{{cite journal |vauthors=Lee TY, Lee C, Choi WJ, Lee JY, Kim HY |title=Synchronous occurrence of primary malignant mixed müllerian tumor in ovary and uterus |journal=Obstet Gynecol Sci |volume=56 |issue=4 |pages=269–72 |date=July 2013 |pmid=24328014 |pmc=3784138 |doi=10.5468/ogs.2013.56.4.269 |url=}}</ref><ref name="pmid28469326">{{cite journal |vauthors=Gupta AJ, Singh M, Rani P, Jain S, Khurana N, Sahu L |title=Malignant mixed mullerian tumor of ovary-scrape cytology: Findings with review of literature |journal=J Cytol |volume=34 |issue=2 |pages=125–126 |date=2017 |pmid=28469326 |pmc=5398022 |doi=10.4103/0970-9371.203568 |url=}}</ref>
* Similarly morphologic and molecular studies have indicated that endometrioid and clear cell carcinoma of the ovaries have their origin in endometriosis. These studies suggest that these tumors arise from endometriomas, the endometriotic cysts that are present outside the normal endometrium.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid19342944">{{cite journal |vauthors=Veras E, Mao TL, Ayhan A, Ueda S, Lai H, Hayran M, Shih IeM, Kurman RJ |title=Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases |journal=Am. J. Surg. Pathol. |volume=33 |issue=6 |pages=844–53 |date=June 2009 |pmid=19342944 |doi=10.1097/PAS.0b013e31819c4271 |url=}}</ref><ref name="pmid9383841">{{cite journal |vauthors=Martin DC |title=Cancer and endometriosis: do we need to be concerned? |journal=Semin. Reprod. Endocrinol. |volume=15 |issue=3 |pages=319–24 |date=1997 |pmid=9383841 |doi=10.1055/s-2008-1068762 |url=}}</ref>
* This theory regarding the origin of endometrioid and clear cell carcinoma of the ovary is supported by the fact that tubal ligation that prevents endometriotic implants into ovary and peritoneum in endometriosis has a protective effect on endometrioid and clear cell type cancers but not on the serous cancer of the ovary because it doesn't occlude the connection between fimbria and the ovaries.<ref name="pmid21683865">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm |journal=Hum. Pathol. |volume=42 |issue=7 |pages=918–31 |date=July 2011 |pmid=21683865 |pmc=3148026 |doi=10.1016/j.humpath.2011.03.003 |url=}}</ref><ref name="pmid19038766">{{cite journal |vauthors=Dubeau L |title=The cell of origin of ovarian epithelial tumours |journal=Lancet Oncol. |volume=9 |issue=12 |pages=1191–7 |date=December 2008 |pmid=19038766 |pmc=4176875 |doi=10.1016/S1470-2045(08)70308-5 |url=}}</ref><ref name="pmid18317228">{{cite journal |vauthors=Kurman RJ, Shih IeM |title=Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications |journal=Int. J. Gynecol. Pathol. |volume=27 |issue=2 |pages=151–60 |date=April 2008 |pmid=18317228 |pmc=2794425 |doi=10.1097/PGP.0b013e318161e4f5 |url=}}</ref><ref name="pmid11570411">{{cite journal |vauthors=Piek JM, van Diest PJ, Zweemer RP, Kenemans P, Verheijen RH |title=Tubal ligation and risk of ovarian cancer |journal=Lancet |volume=358 |issue=9284 |pages=844 |date=September 2001 |pmid=11570411 |doi=10.1016/S0140-6736(01)05992-X |url=}}</ref><ref name="pmid8922304">{{cite journal |vauthors=Rosenblatt KA, Thomas DB |title=Reduced risk of ovarian cancer in women with a tubal ligation or hysterectomy. The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives |journal=Cancer Epidemiol. Biomarkers Prev. |volume=5 |issue=11 |pages=933–5 |date=November 1996 |pmid=8922304 |doi= |url=}}</ref>


==== The origin of mucinous tumors of gastrointestinal type and transitional cell (Brenner) tumors: Still a mystery to solve ====
==== The origin of mucinous tumors of gastrointestinal type and transitional cell (Brenner) tumors: Still a mystery to solve ====

Revision as of 16:16, 25 February 2019


Template:Epithelial ovarian cancer Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]


The origin of mucinous tumors of gastrointestinal type and transitional cell (Brenner) tumors: Still a mystery to solve

  • Mucinous and the transitional tumors of ovaries are two of the least common types of the epithelial ovarian tumors. In fact, most of the mucinous tumors in ovaries are secondary and primary tumors only form about 3% of all epithelial ovarian cancers.
  • Mucinous epithelium in mucinous tumors of ovaries resemble more to intestinal mucinous epithelium rather than that of endocervix as was previously argued. Transitional cell tumors, on the other hand, are closer to bladder epithelium in histological studies.
  • Another study demonstrated the presence of Brenner tumor foci in mucinous cystadenoma in almost one fifth of the cases. Alternatively the association of mucinous tumors with Walthard cell nests, which are composed of transitional-type epithelium, also indicates the connection between mucinous and transitional tumors.
  • ARIDA loss and PIK3CA activation in clear cell cancer of ovaries.[1](A)  ARID1A and PIK3CA alterations plot against TCGA datasets. Significance of association between ARID1A and PIK3CA mutations were determined using Fisher’s exact test. (B) Determination of CRE-deleted (Arid1aΔ) allele in samples of tumor DNA. (C) RT-PCR was used to detect ARID1A loss or (Gt)Rosa26Pik3ca*H1047R transcripts.  (D and E) Expression of ARID1A in normal ovaries (E) Expression of ARID1A in the normal ovarian surface epithelium (arrowhead). (F) ARID1A expression is not observed in the tumors. (H, I) Highest expression of P-AKT S473 in surface epithelium of ovaries in normal ovaries (E, arrowhead) and are greatly increased in ovarian tumors (F, arrowhead). Asterisk in E denotes an oocyte. (J,K) Morbid Arid1afl/fl;(Gt)Rosa26Pik3ca*H1047R mouse at sacrifice with hemorrhagic ascites (inset), primary ovarian tumor of moderate size, and bilateral tumor metastases (arrowheads). (L,M) Morbid Arid1afl/fl;(Gt)Rosa26Pik3ca*H1047R mouse at sacrifice with hemorrhagic ascites (inset), large primary ovarian tumor, and no visible metastases. The mice shown in J-M were sacrificed at 7 and 9 weeks post-AdCRE, respectively, because of visible ascitic fluid burden. (N,O) Arid1afl/+;(Gt)Rosa26Pik3ca*H1047R mice at 11-weeks post-AdCRE showing no evidence for tumor formation. In K and M, dashed circles indicate primary ovarian tumor on injected ovary. In N, arrows denote the AdCRE injected ovary. In K, M, and O, asterisks denote the uninjected, control ovary.

References

  1. ↑ Chandler RL, Damrauer JS, Raab JR, Schisler JC, Wilkerson MD, Didion JP, Starmer J, Serber D, Yee D, Xiong J, Darr DB, Pardo-Manuel de Villena F, Kim WY, Magnuson T (January 2015). "Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling". Nat Commun. 6: 6118. doi:10.1038/ncomms7118. PMC 4308813. PMID 25625625.
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