Ovarian Carcinoma

Ovarian carcinoma is a deadly disease. Ovarian epithelial carcinoma is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women, with around 50% of all cases occurring in women older than 63 years. Ovarian cancer is the ninth most common cancer in women. Most women with advanced ovarian cancer die from this disease.

Classification of ovarian carcinoma 

On the basis of histopathological examination, pathologists classify ovarian carcinoma into 4 types:

1) Serous carcinoma

2) Clear cell carcinoma

3) Endometrioid carcinoma

4) Mucinous carcinoma

 

Epidemiology

Ovarian carcinoma is more frequent in developed countries except Japan. In the United States 1 out of 71 women have a chance of developing an ovarian cancer in their life time. The median age of detection of this disease is 61. The disease is more common in older women, and more common in white than African-American women.

Symptoms

The following symptoms are frequent in ovarian cancer patients:

The major symptoms

  • Continuous pelvic and abdominal pain
  • Swelling of abdomen
  • Loss of appetite

Other symptoms

  • Rectal bleeding
  • Change in bowel habits
  • Urinary symptoms
  • Back pain
  • Extreme fatigue
  • Postmenopausal bleeding

Risk factors

Age

The chances of developing this disease increases with age. The risk is very high in women who have crossed menopause.

Family or personal history of ovarian cancer, breast cancer, or colorectal cancer

Ovarian cancer can be inherited. It can come from mother’s side or father’s side. Mutations in genes associated with breast and colorectal cancer also causes ovarian cancer. Some of these mutations are mentioned later. Therefore, a person who had breast cancer or colorectal cancer has a risk of developing of ovarian cancer later in her life. BRCA1 and BRCA2 are the most common genes increasing cancer risk.

Genetics

Obesity

Obese women are more prone to developing ovarian cancer.

Reproductive history

Pregnancy and breast feeding lowers the risk of ovarian cancer. A woman who has given birth to a child has less risk of having ovarian cancer.

Infertility treatment

Infertility or infertility treatment may be associated with increased risk of developing ovarian cancer. Use of fertility drugs may increase the chances of developing ovarian cancer. But, this association is controversial. A study in Denmark has shown that intake of fertility drug does not have any relation to increase in risk of developing ovarian cancer.

Other gynecological treatments

Taking birth control pills may lower the risk of ovarian cancer, as may tubal ligation as well as hysterectomy.

Androgens

Androgens are male hormones. Women who take androgens or drugs like Danazol, that increases androgen levels, may be prone to developing ovarian cancer.

Estrogen therapy

Risk of ovarian cancer increases with intake of estrogen after menopause. The risk can be decreased by taking progesterone along with estrogen, although that may raise the risk of other cancers.

Diet

High-fat diet can increase the risk of ovarian cancer. Vegetables in the diet lower the risk.

Diagnosis

Physical exam: The first step is a pelvic exam by a physician to see if there is a mass or an enlarged ovary.

Ultrasound and Transvaginal ultrasound: The ultrasound device can give pictures of the affected regions. The images can be assessed for detection of ovarian tumors. For a better view of the ovaries, the device may be inserted into the vagina (transvaginal ultrasound). The transvaginal ultrasound gives a good magnified view of reproductive organs and can detect the presence of tumors.

CT scans and MRI scans: These techniques provide clear images of the organs. The images can be studies to detect any abnormalities in the ovary.

Chest X-ray: The chest X- ray is performed to detect may show pleural effusions. A pleural effusion can also be a symptom of several types of cancer. Other than being a symptom of ovarian cancers this can also happen in case of breast cancer, lung cancer and lymphomas. A chest X-ray may also masses if cancer has spread.

Barium enema and intravenous pyelography (IVP): These tests may also be suggested to measure the size of the mass.

Laparotomy, biopsy, and surgical staging: Laparotomy is a surgery to remove tissue and fluid from the pelvis and abdomen. The removal of tissue from the affected site is called biopsy. These samples are examined under microscope to detect ovarian cancer cells.

There are tests for biochemical markers in blood samples. However, these tests are not useful for screening or diagnosis.  They may be used to follow patients after treatment.

  • Cancer antigen-125 (CA-125): This protein is secreted by epithelial ovarian tumors. This is an important marker for ovarian cancer and can be detected in 9 out of 10 patients at advanced stage. At early stage of the disease, CA-125 can be detected in 5 out of 10 patients. But, this marker is not specific for ovarian carcinoma only. High amount of this protein is also detectable in patients with menstrual disorders, other malignancies, benign ovarian tumors, endometriosis, pregnancy, and pelvic inflammatory disease. This marker can be used to assess improvement of a patient after treatment.
  • Human chorionic gonadotropin: This is a glycoprotein hormone produced by some germ cell ovarian tumors (dysgerminomas), choriocarcinomas and embryonal carcinomas. It is also produced during pregnancy.
  • Inhibin: Some granulosa cell tumors secrete this hormone.
  • Alpha-fetoprotein: Endodermal sinus tumors secrete this protein
  • Lactate dehydrogenase: Germ cell tumors secrete this enzyme.

Genetics and molecular pathology of ovarian cancer

Many genetic changes are involved in the development of both sporadic and hereditary cases of ovarian cancer. The genetic changes are related to the activation of oncogene(s) and inactivation of tumor suppressor gene(s).

Genetic alterations associated with histological subtypes of ovarian carcinomas:

High-grade serous and possibly endometrioid carcinomas: Mutations in TP53, BRCA1 and/or BRCA2

Low-grade serous carcinomas: Mutations in KRAS and BRAF and activation of RAS-RAF signaling pathway.

Mucinous carcinomas: Mutation in KRAS.

Low-grade endometrioid carcinomas: Mutations in CTNNB1 (which encodes β-catenin) and PTEN.

Treatment

Surgery

Surgery is the mainstay treatment. A laparatomy is done and the affected tissues are removed. The tissues can be assessed for staging the cancer. If the cancer has spread, the surgeon removes as much cancer as possible. This is called “debulking” surgery. Women at a young age may prefer to have one ovary fallopian tube, and the omentum (fat around the intestines) removed.

Chemotherapy

Multi-agent chemotherapy can be combined with surgery. Chemotherapy can be used before or after the surgery depending on the situation. Platinum-based therapy (cisplatin or carboplatin) alone or combined with Paclitaxel can be used following surgery. The same drugs can be used again if relapse occurs. If patients are allergic to platinum-based drugs, pegylated liposomal doxorubicin hydrochloride (PLDH) is used for subsequent treatment.

Radiotherapy

Radiotherapy is not preferred to chemotherapy if the disease has advanced beyond stage II. Therefore, chemotherapy is preferred because of fewer side effects.

Prognosis

Overall, 5-year survival in ovarian epithelial carcinoma is low. This is mainly because of late diagnosis of the disease. Patients who are younger (below 50 years) have a better prognosis. The disease has a good prognosis if detected and treated early. But, the chances of survival go down with the progression of the disease. At stage III and IV, the 5-year survivals are only about 20 % and 5 % respectively. This clearly indicates that the prognosis is very poor if detected after the disease has spread.

References

  1. Bharwani N, Reznek RH, Rockall AG. (2011) Ovarian Cancer Management: the role of imaging and diagnostic challenges. Eur J Radiol.;78(1):41-51.
  2. Ramirez I, Chon HS, Apte SM. (2011) The role of surgery in the management of epithelial ovarian cancer. Cancer Control.;18(1):22-30.
  3. Cragun JM. (2011) Screening for ovarian cancer. Cancer Control.;18(1):16-21. Review.
  4. Yawn BP, Barrette BA, Wollan PC. (2004) Ovarian cancer: the neglected diagnosis; Mayo Clin Proc. ; 79(10):1277-82.
  5. Stephen A. Cannistra, M.D. (2004) Cancer of the Ovary; N Engl J Med; 351:2519-2529
  6. Nancy wang (2002) Cytogenetics and Molecular Genetics of Ovarian Cancer; American Journal of Medical Genetics (Semin. Med. Genet.) 115:157–163
  7. Shelling AN, Foulkes W. (2001) Molecular genetics of ovarian cancer. Mol Biotechnol. Sep;19(1):13-28.
  8. Bell DA. (2005) Origins and molecular pathology of ovarian cancer. Mod Pathol.;18 Suppl 2:S19-32.
  9. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.