Targeting master regulators with general transcription inhibitors in clear cell ovarian cancer

AbstractRecent studies have reported cancer-associated mutations in normal endometrium. Mutations in eutopic endometrium may lead to endometriosis and endometriosis-associated ovarian cancer. We investigated PIK3CA mutations (PIK3CAm) for three hotspots (E542K, E545K, H1047R) in eutopic endometrium in patients with ovarian cancer and endometriosis from formalin-fixed paraffin-embedded specimens by laser-capture microdissection and droplet digital PCR. The presence of PIK3CAm in eutopic endometrial glands with mutant allele frequency ≥ 15% were as follows: ovarian clear cell carcinoma (OCCC) with PIK3CAm in tumors, 20/300 hotspots in 11/14 cases; OCCC without PIK3CAm, 42/78 hotspots in 11/12 cases; high-grade serous ovarian carcinoma, 8/45 hotspots in 3/5 cases; and endometriotic cysts, 5/63 hotspots in 5/6 cases. These rates were more frequent than in noncancer nonendometriosis controls (7/309 hotspots in 5/17 cases). In OCCC without PIK3CAm, 7/12 (58%) cases showed multiple hotspot mutations in the same eutopic endometrial glands. In 3/54 (5.6%) cases, PIK3CAm was found in eutopic endometrial stroma. Multisampling of the OCCC tumors with PIK3CAm showed intratumor heterogeneity in three of eight cases. In two cases, PIK3CAm was detected in the stromal component of the tumor. Homogenous PIK3CAm in the epithelial component of the tumor matched the mutation in eutopic endometrial glands in only one case. Eutopic endometrial glands in ovarian cancer and endometriosis show high frequency of PIK3CAm that is not consistent with tumors, and multiple hotspot mutations are often found in the same glands. While the mutations identified in eutopic endometrium may not be driver mutations in the patient’s cancer, these are still driver mutations but this specific clone has not undergone the requisite steps for the development of cancer.

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Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs

Human Pathology ◽

10.1016/j.humpath.2006.06.026 ◽

2007 ◽

Vol 38 (1) ◽

pp. 134-139 ◽

Cited By ~ 18

Author(s):

Sadako Nishimura ◽

Hiroshi Tsuda ◽

Kiyoshi Ito ◽

Toshiko Jobo ◽

Nobuo Yaegashi ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Differential Expression ◽

Clear Cell ◽

Histologic Types

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Protein expression levels of excision repair cross-complementation group 1 and xeroderma pigmentosum D correlate with response to platinum-based chemotherapy in the patients with advanced epithelial ovarian cancer

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2007.01155.x ◽

2008 ◽

Vol 18 (5) ◽

pp. 1007-1012 ◽

Cited By ~ 8

Author(s):

K. Lin ◽

D. Ye ◽

X. Xie

Keyword(s):

Ovarian Cancer ◽

Protein Expression ◽

Clear Cell ◽

Excision Repair ◽

Cell Cancer ◽

Complementation Group ◽

Serous Ovarian Cancer ◽

Expression Levels ◽

Platinum Based Chemotherapy ◽

Group 1

This study was undertaken to examine whether there is an association between excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum D (XPD) protein expression levels and response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). The study cohort consisted of 91 consecutive patients suffering from stage III or IV disease of primary EOC from 1999 to 2004 at the Women's Hospital, School of Medicine, Zhejiang University. There were 36 sensitive cases of serous ovarian cancer, 27 resistant cases of serous ovarian cancer, 15 cases of clear cell cancer, and 13 cases with serous ovarian cancer receiving neoadjuvant chemotherapy. The ovarian tissue microsections were stained by standard immunohistochemical techniques to show ERCC1 and XPD protein expression levels. In resistance group of serous ovarian cancer, ERCC1 and XPD protein expression levels were significantly higher than those of sensitivity group, and after receiving neoadjuvant chemotherapy, they showed 23% and 32% higher than before. Meanwhile, their levels of clear cell cancer group were significantly higher than serous ovarian cancer group's. Upregulation of ERCC1 and XPD protein expression was associated with resistance process to platinum-based chemotherapy in advanced EOC. This study provided evidence that differences of nucleotide excision repair–related genes expression may have an effect on the observed differences in clinical behavior of EOC

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MiR‑381 regulates cell motility, growth and colony formation through PIK3CA in endometriosis‑associated clear cell and endometrioid ovarian cancer

Oncology Reports ◽

10.3892/or.2018.6779 ◽

2018 ◽

Cited By ~ 3

Author(s):

Chia‑Yi Hsu ◽

Tsung‑Hua Hsieh ◽

Tze‑Kiong Er ◽

Hung‑Sheng Chen ◽

Ching‑Chou Tsai ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Motility ◽

Colony Formation ◽

Clear Cell ◽

Endometrioid Ovarian Cancer

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Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell, non-mucinous histology

Journal of Gynecologic Oncology ◽

10.3802/jgo.2014.25.1.43 ◽

2014 ◽

Vol 25 (1) ◽

pp. 43 ◽

Cited By ~ 8

Author(s):

Hiroaki Kajiyama ◽

Kiyosumi Shibata ◽

Mika Mizuno ◽

Tomokazu Umezu ◽

Shiro Suzuki ◽

...

Keyword(s):

Ovarian Cancer ◽

Survival Benefit ◽

Clear Cell ◽

Recurrent Ovarian Cancer ◽

Mucinous Histology

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Association of age at menarche, parity, and hormonal contraceptive use with the histologic type of ovarian cancer

Majalah Obstetri & Ginekologi ◽

10.20473/mog.v29i32021.118-123 ◽

2021 ◽

Vol 29 (3) ◽

pp. 118

Author(s):

Firda Azizah ◽

Pungky Mulawardhana ◽

Willy Sandhika

Keyword(s):

Ovarian Cancer ◽

Contraceptive Use ◽

Clear Cell ◽

Hormonal Contraceptive ◽

Age At Menarche ◽

Histologic Type ◽

Cross Sectional ◽

Number Of Patients ◽

The Relationship ◽

Age Of Menarche

HIGHLIGHT1. Relationship between age at menarche, parity, and contraceptive use with histologic type of ovarian cancer was analyzed. 2. A number of patients with ovarian cancer were analytically observed with retrospective cross-sectional approach and the histologic types of the cancer were determined.3. Age of menarche, parity, and hormonal contraceptive use was found not to have significant correlation with histologic type of ovarian cancer. ABSTRACTObjectives: This study analyze the relationship between age at menarche, parity, and contraceptive use with histologic type of ovarian cancer.Materials and Methods: This study used an observational analytic with a retrospective cross-sectional approach. The research samples were 128 patients with ovarian cancer at RSUD Dr. Saiful Anwar Malang in 2017-2019, all patients underwent primary staging laparotomy. The histologic type of ovarian cancer consist of: serous 45, mucinous 45, endometrioid 10, clear cell 20, and others 4. Data analysis using chi square.Results: The p value for the relationship between the age of menarche and histologic type of ovarian cancer was p = 0.500 (p> 0.05), parity p = 0.313, and contraceptive use p = 0.824. The distribution of clear cell was more common in multiparous, 40% of endometrioid found in nulliparous, serous were more common in women with hormonal contraceptive use >5 years, whereas mucinous were more common in history of use <5 years.Conclusion: There was no significant relationship between the age of menarche, parity, and hormonal contraceptive use on histologic type of ovarian cancer.

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