Epithelial ovarian cancer: Difference between revisions

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* 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>
* 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>  
* 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>
* 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>


==== 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 16:08, 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 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.[1][2][3]
  • 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.[1][2][3][4][5]
  • 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.[1][2][3][6][7].
  • 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.[1][2][3][6][8][9]
  • 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.[1][2][3][6][8][9]
  • 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.[1][2][3][10][6][11]
  • 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.[1][2][3][12][13]
  • 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.[1][2][3][4][5]
  • 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.[1][2][3][14]

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.[15](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. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Kurman RJ, Shih I (July 2011). "Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm". Hum. Pathol. 42 (7): 918–31. doi:10.1016/j.humpath.2011.03.003. PMC 3148026. PMID 21683865. Vancouver style error: initials (help)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Dubeau L (December 2008). "The cell of origin of ovarian epithelial tumours". Lancet Oncol. 9 (12): 1191–7. doi:10.1016/S1470-2045(08)70308-5. PMC 4176875. PMID 19038766.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Kurman RJ, Shih I (April 2008). "Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications". Int. J. Gynecol. Pathol. 27 (2): 151–60. doi:10.1097/PGP.0b013e318161e4f5. PMC 2794425. PMID 18317228. Vancouver style error: initials (help)
  4. ↑ 4.0 4.1 Veras E, Mao TL, Ayhan A, Ueda S, Lai H, Hayran M, Shih I, Kurman RJ (June 2009). "Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases". Am. J. Surg. Pathol. 33 (6): 844–53. doi:10.1097/PAS.0b013e31819c4271. PMID 19342944. Vancouver style error: initials (help)
  5. ↑ 5.0 5.1 Martin DC (1997). "Cancer and endometriosis: do we need to be concerned?". Semin. Reprod. Endocrinol. 15 (3): 319–24. doi:10.1055/s-2008-1068762. PMID 9383841.
  6. ↑ 6.0 6.1 6.2 6.3 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 (February 2007). "Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship". Am. J. Surg. Pathol. 31 (2): 161–9. doi:10.1097/01.pas.0000213335.40358.47. PMID 17255760.
  7. ↑ 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 (September 2005). "Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon". Clin. Cancer Res. 11 (17): 6116–26. doi:10.1158/1078-0432.CCR-04-2509. PMID 16144910.
  8. ↑ 8.0 8.1 Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, Gille JJ, Jongsma AP, Pals G, Kenemans P, Verheijen RH (November 2001). "Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer". J. Pathol. 195 (4): 451–6. doi:10.1002/path.1000. PMID 11745677.
  9. ↑ 9.0 9.1 Callahan MJ, Crum CP, Medeiros F, Kindelberger DW, Elvin JA, Garber JE, Feltmate CM, Berkowitz RS, Muto MG (September 2007). "Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction". J. Clin. Oncol. 25 (25): 3985–90. doi:10.1200/JCO.2007.12.2622. PMID 17761984.
  10. ↑ Piek JM, Verheijen RH, Kenemans P, Massuger LF, Bulten H, van Diest PJ (August 2003). "BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis". Gynecol. Oncol. 90 (2): 491. PMID 12893227.
  11. ↑ Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP (February 2006). "The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome". Am. J. Surg. Pathol. 30 (2): 230–6. PMID 16434898.
  12. ↑ Lee TY, Lee C, Choi WJ, Lee JY, Kim HY (July 2013). "Synchronous occurrence of primary malignant mixed müllerian tumor in ovary and uterus". Obstet Gynecol Sci. 56 (4): 269–72. doi:10.5468/ogs.2013.56.4.269. PMC 3784138. PMID 24328014.
  13. ↑ Gupta AJ, Singh M, Rani P, Jain S, Khurana N, Sahu L (2017). "Malignant mixed mullerian tumor of ovary-scrape cytology: Findings with review of literature". J Cytol. 34 (2): 125–126. doi:10.4103/0970-9371.203568. PMC 5398022. PMID 28469326.
  14. ↑ Piek JM, van Diest PJ, Zweemer RP, Kenemans P, Verheijen RH (September 2001). "Tubal ligation and risk of ovarian cancer". Lancet. 358 (9284): 844. doi:10.1016/S0140-6736(01)05992-X. PMID 11570411.
  15. ↑ 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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