Ovarian Cancer genes

Molecular Profiling of Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer death in the United States, with an estimated 22,280 new cases and 14,240 deaths estimated for 2016 (ACS 2016). The vast majority of women are diagnosed with advanced stage EOC. Current practice consists of aggressive surgical removal of tumors, followed by platinum–taxane based chemotherapy (Muggia 2009). Despite initial aggressive treatment, most tumors recur, and the overall 5-year survival rate is 44% (Siegel, Naishadham, and Jemal 2012).

Emerging knowledge about underlying molecular alterations in ovarian cancer could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies. Approximately 10–20% of high grade ovarian cancers are associated with germline mutations in BRCA1/2 (Pal et al. 2005). Somatic alterations in BRCA1/2 and other genes associated with DNA repair are seen in approximately 50% of high grade ovarian cancers (TCGA 2011) and tumors with a ‘BRCAness’ molecular profile are relatively sensitive to treatment with DNA damaging agents cisplatin and PARP inhibitors (Konstantinopoulos et al. 2010).

More recently, EOC tumors have been broadly classified into two distinct groups with unique histological, clinical and molecular profiles (Table 1). Type I tumors have low grade serous, clear cell, endometrioid, and mucinous histological features. Typically, these tumors are slow growing and confined to the ovary, and are less sensitive to standard chemotherapy. BRAF and KRAS somatic mutations are relatively common in these tumors, which may have important therapeutic implications.

Type II tumors are high grade serous cancers of the ovary, peritoneum, and fallopian tube. Other high grade endometrioid and poorly differentiated ovarian cancers as well as carcinosarcomas are included in the type II group. These tumors are clinically aggressive and are often widely metastatic at the time of presentation. High grade serous EOC tumors display high levels of genomic instability with few common mutations, other than TP53, which is altered in over 90% of the cases (Kurman and Shih 2011; Landen, Birrer, and Sood 2008; TCGA 2011). PIK3CA and RAS signaling pathways are altered in 45% of the cases, but somatic mutations are rare and gene amplifications are far more common (TCGA 2011).


Currently, the most common ‘actionable’ alterations with potential for small molecule targeted therapy in EOC tumors are in the PIK3CA/PTEN and KRAS/BRAF signaling pathways.

Table 1. Frequency of Somatic Gene Mutations in Epithelial Ovarian Cancer (EOC)

Gene Mutation EOC Overall High Grade Serous (Type II) Low Grade Serous (Type I) Clear Cell (Type I) Endometrioid (Type I) Mucinous (Type I)
BRAF 11% (Kurman and Shih 2011) <1% (TCGA 2011) 24–33% (Nakayama et al. 2006Singer et al. 2003) 1% (Kuo et al. 2009) 24% (Singer et al. 2003) 50–75% (Gemignani et al. 2003)
KRAS 11% (Kurman and Shih 2011) <1% (TCGA 2011) 33% (Nakayama et al. 2006Singer et al. 2003) <1–7% (Kuo et al. 2009; Singer et al. 2003) <1% (Singer et al. 2003) 50–75% (Gemignani et al. 2003)
PIK3CA 6.7% (Campbell, Russell, and Phillips 2005; Levine et al. 2005; Wang et al. 2005) <1% (TCGA 2011) 5% (Nakayama et al. 2006) 20–33% (Campbell et al. 2004; Kuo et al. 2009) 20% (Campbell et al. 2004) Rare
PTEN 20% (Kurman and Shih 2011) <1% mutation(TCGA 2011) 20% (Landen, Birrer, and Sood 2008) <1–5% (Kuo et al. 2009; Willner et al. 2007) 20–31% (Kurman and Shih 2011; Willner et al. 2007) Rare


Contributors: Oluwole Fadare, M.D., Dineo Khabele, M.D.

Suggested Citation: Fadare, O., D. Khabele. 2016. Molecular Profiling of Epithelial Ovarian Cancer. My Cancer Genomehttps://www.mycancergenome.org/content/disease/ovarian-cancer/ (Updated January 26).

Last Updated: January 26, 2016

Disclaimer: The information presented at MyCancerGenome.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.

Can hirsutism get reduced over time?

Can hirsutism get reduced over time? by Connie b. Dellobuono

Answer by Connie b. Dellobuono:

See a doctor. I would avoid estrogen rich food and eat more progesterone rich food. There is cell energy herbal caps at http://www.getwellinternational.com that removes excess estrogen.
From Wiki:
Hirsutism can be caused by either an increased level of androgens, the male hormones, or an oversensitivity of hair follicles to androgens. Male hormones such as testosterone stimulate hair growth, increase size and intensify the growth and pigmentation of hair. Other symptoms associated with a high level of male hormones include acne, deepening of the voice, and increased muscle mass.
Growing evidence implicates high circulating levels of insulin in women for the development of hirsutism. This theory is speculated to be consistent with the observation that obese (and thus presumably insulin resistant hyperinsulinemic) women are at high risk of becoming hirsute. Further, treatments that lower insulin levels will lead to a reduction in hirsutism.
It is speculated that insulin, at high enough concentration, stimulates the ovarian theca cells to produce androgens. There may also be an effect of high levels of insulin to activate insulin-like growth factor 1 (IGF-1) receptor in those same cells. Again, the result is increased androgen production.
Signs that are suggestive of an androgen-secreting tumor in a patient with hirsutism is rapid onset, virilization and palpable abdominal mass.
The following may be some of the conditions that may increase a woman’s normally low level of male hormones:
Adrenal gland cancer, Von Hippel–Lindau disease.
Congenital adrenal hyperplasia, in turn mostly caused by 21-α hydroxylase deficiency.
Cushing’s disease.
Growth hormone excess (acromegaly).
Insulin resistance.
Obesity: As there is peripheral conversion of androgens to estrogen in these patients, this is the same mechanism as polycystic ovary syndrome, PCOS.
Polycystic ovary syndrome (PCOS), the most common cause in ciswomen.
Porphyria cutanea tarda.
Stromal hyperthecosis (SH) – in postmenopausal women.
Transsexualism (male birth sex)
Tumors in the ovaries .
Use of certain medications such as tetrahydrogestrinone, phenytoin, or minoxidil.
Dr Mercola wrote about PCOS: You can’t just take progesterone, and you can’t just cut out the sugar. You usually need to do both. Exercise and good nutrition are also very important in maintaining hormone balance.
Do avoid plastics and chemicals that alter our hormonal balance. Do a liver detox. Eat more cilantro and sulfur rich foods.

Can hirsutisum get reduced over time?