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ovarian carcinomas

Monday 23 August 2004

primary ovarian epithelial carcinoma POEC , Epithelial ovarian cancer

Definition: Ovarian carcinomas are currently classified into 5 main histologic types:
- ovarian high-grade serous carcinoma (HGSC),
- ovarian clear cell carcinoma (CCC),
- ovarian endometrioid carcinoma
- ovarian mucinous adenocarcinoma
- ovarian low-grade serous carcinoma (LGSC)


- ovarian carcinogenesis

Digital case

- JRC:8985 : Ovarian serous cystadenocarcinoma.


Ovarian carcinoma is the leading cause of death from gynecologic cancer and one of the most frequent causes of fatal malignancy in women. The poor prognosis is likely related to the degree of peritoneal dissemination associated with ascites accumulation.

Approximately 25,000 ovarian cancers are diagnosed in the U.S. annually. 75% of cases diagnosed in the advanced stage when they are largely incurable. Ovarian cancer is the most lethal gynecologic malignancy.


- Type 1

One group of tumors, designated type I, is composed of :
- low-grade serous carcinoma,
- low-grade endometrioid carcinoma,
- clear cell carcinoma,
- mucinous carcinoma
- transitional (Brenner) carcinoma.

These tumors generally behave in an indolent fashion, are confined to the ovary at presentation and, as a group, are relatively genetically stable.

They lack mutations of TP53, but each histologic type exhibits a distinctive molecular genetic profile. Moreover, the carcinomas exhibit a shared lineage with the corresponding benign cystic neoplasm, often through an intermediate (borderline tumor) step, supporting the morphologic continuum of tumor progression.

- Type 2

In contrast, another group of tumors, designated type II, is highly aggressive, evolves rapidly and almost always presents in advanced stage.

Type II tumors include:
- conventional high-grade serous carcinoma,
- undifferentiated carcinoma,
- malignant mixed mesodermal tumors (carcinosarcoma).

They display TP53 mutations in over 80% of cases and rarely harbor the mutations that are found in the type I tumors.

What have been traditionally thought to be primary ovarian tumors actually originate in other pelvic organs and involve the ovary secondarily. Thus, it has been proposed that serous tumors arise from the implantation of epithelium (benign or malignant) from the fallopian tube.

Endometrioid and clear cell tumors have been associated with endometriosis that is regarded as the precursor of these tumors. As it is generally accepted that endometriosis develops from endometrial tissue by retrograde menstruation, it is reasonable to assume that the endometrium is the source of these ovarian neoplasms.

Finally, preliminary data suggest that mucinous and transitional (Brenner tumor) tumors arise from transitional-type epithelial nests at the tubal-mesothelial junction by a process of metaplasia.

Differential diagnosis

- ovarian metastasis (24455652)

  • The most common tumors metastasizing to the ovary originate from the gastrointestinal tract followed by the endometrium.
  • A panel of six markers including cytokeratin-7 (CK7), CK20, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), estrogen receptor (ER) and Wilms’ tumor 1 (WT1) can help to classify various surface epithelial tumors as well as to differentiate them from tumors metastatic to the ovary.
  • CK7 is the most helpful marker to differentiate primary ovarian carcinoma from metastatic colorectal carcinoma of the ovary.
  • Nearly, 96% of ovarian adenocarcinomas were positive for CK7 in contrast to metastatic colorectal, which showed only 25% positivity.
  • CK7, CK20 and CEA are useful markers to differentiate primary serous tumors from primary mucinous tumors; however, these are less helpful in differentiating ovarian mucinous adenocarcinomas from colorectal adenocarcinomas metastasizing to the ovaries.
  • WT1 helps in typing primary surface epithelial tumors of the ovary and is also significant in determining whether a serous carcinoma within the ovary is primary or metastatic.


- An Immunohistochemical Algorithm for Ovarian Carcinoma Typing


- 8p12-p23


- 20q amplification


- susceptibility loci

  • 9p22 (BNC2)
  • 19p13 (20852633)
  • 8q24
  • 2q31
    - two loci approaching genome-wide significance at 3q25 and 17q21


  • Opioid binding protein cell adhesion molecule (OPCML) is frequently epigenetically inactivated in epithelial ovarian cancers, with tumor suppressor function in vitro and in vivo.
  • OPCML functions by a novel mechanism in epithelial ovarian cancer cell lines and normal ovarian surface epithelial cells by regulating a specific repertoire of receptor tyrosine kinases: EPHA2, FGFR1, FGFR3, HER2, and HER4.
  • OPCML negatively regulates receptor tyrosine kinases by binding their extracellular domains, altering trafficking via nonclathrin-dependent endocytosis, and promoting their degradation via a polyubiquitination-associated proteasomal mechanism leading to signaling and growth inhibition.
  • Exogenous recombinant OPCML domain 1–3 protein inhibited the cell growth of epithelial ovarian cancers cell in vitro and in vivo in 2 murine ovarian cancer intraperitoneal models that used an identical mechanism.

See also

- ovarian tumors

Open references

- Immunohistochemistry: A diagnostic aid in differentiating primary epithelial ovarian tumors and tumors metastatic to the ovary. Kriplani D, Patel MM.
South Asian J Cancer. 2013 Oct;2(4):254-8. doi : 10.4103/2278-330X.119888 PMID: 24455652 (Free)


- Common variants at 19p13 are associated with susceptibility to ovarian cancer. Bolton KL, Tyrer J, Song H, Ramus SJ et al. Nat Genet. 2010 Sep 19. PMID: 20852633

- A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Goode EL, Chenevix-Trench G, Song H, Ramus SJ et al. Nat Genet. 2010 Sep 19. PMID: 20852632

- The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory. Kurman RJ, Shih IM. Am J Surg Pathol. 2010 Feb 11. PMID: 20154587