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ovarian serous carcinoma

Monday 3 September 2007

Ovarian serous cystadenocarcinoma; ovarian serous adenocarcinoma; Ovarian papillary serous carcinoma


Definition: Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade.

Ovarian papillary serous carcinoma has fibrovascular papillae. It is high grade (pleomorphic with nucleoli), or low grade (uniform cells +/- nucleoli). By IHC, it is positive for p16, ER, WT-1, IMP3, and p53.


- High-grade Serous Carcinoma

- High grade Serous carcinoma

- Serous carcinoma, ovary or peritoneum

- ovary serous carcinoma with squamous differentiation

Digital case

- JRC:8985 : Ovarian serous cystadenocarcinoma.

Invasive well-differentiated serous carcinoma, or "invasive low-grade micropapillary serous carcinoma," is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features.

Subclassification of high-grade serous carcinoma into moderately and poorly differentiated could be not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma. (18769340)


- low-grade ovarian serous adenocarcinoma
- high-grade ovarian serous adenocarcinoma

A 2-tier grading system based on nuclear grade divides ovarian serous carcinomas into low (nuclear grade 1) and high grade (nuclear grade 3).


- macropapillary pattern of invasion (18779727)
- invasive micropapillary serous carcinoma (MPSC)


WT1 : Positive (78%)
CA125 : Positive (78%)
CK5/6 : Positive (55%)
CEA : Usually Negative
ER : +/- (50%)
PR : +/- (50%)
CK7 : Usually Positive
CK20 : Usually Negative

Comment: WT-1 is one of the most useful stains for ovarian serous carcinoma, as the specificity of CA-125 is more limited. However, in the setting of a differential diagnosis with mesothelioma, WT-1 is not useful.

References: Nofech-Moses, S., et. al. "Immunophenotyping of Serous Carcinoma of the Female Genital Tract." Mod Pathol. 2008 Sep;21(9);1147-55.

Molecular biology

Mutations in KRAS, BRAF, and ERBB2 genes characterize most low-grade serous carcinomas. (19461510)

90.9% (10/11) of "intermediate" (nuclear grade 2) tumors contain nonsynonymous TP53 mutations characteristic of high-grade serous carcinomas. The molecular genetic profile and behavior of serous carcinomas with grade 2 nuclei are virtually the same as those of serous carcinomas with grade 3 nuclei, supporting the use of the 2-tier grading system for classifying ovarian serous carcinomas. (19461510)


- CGH gains

  • 1p36.33 gains
  • 3q26.2 gains (16845658)
  • 8q24.3 gains
  • 10q26.3 gains
  • 12p11.21 gains
  • 20q13.33 gains (16845658)
  • 21q22.3 gains

- CGH losses

  • 4p12 losses
  • 4q losses (16845658)
  • 5q13.2 losses (16845658)
  • 7q11.21 losses
  • 8p23.1 losses
  • 13q losses (high-grade carcinomas) (16845658)
  • 14q32.33 losses
  • Xq13.3 losses
  • Xq21.31 losses

- High-level regional amplifications

NB: The gains on 5p15.33 and 14q11.2, and losses on 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, and 22q12.3 were more frequent in chemoresistant disease. The most reliable combination of chromosomal aberrations for detecting chemoresistant disease was the loss on 13q32.1 and 8p21.1 (AUC 0.950).

NB: The most striking difference between low-grade and high-grade serous carcinomas was seen in a higher incidence of chromosomal gains at 3q and 20q and losses of 13q in the high-grade carcinomas. In addition, high-level amplifications were significantly more frequent in high-grade carcinomas, specifically involving regions on 3q and 8q. Chromosomal amplifications of 19p and 19q and losses of 4q and 5q were among the most frequent changes found in both low-grade and high-grade carcinomas, distinguishing them from borderline tumors, which had very few recurrent alterations. (16845658)

See also

- ovarian tumors


- Defining the Cut Point Between Low-grade and High-grade Ovarian Serous Carcinomas: A Clinicopathologic and Molecular Genetic Analysis. Ayhan A, Kurman RJ, Yemelyanova A, Vang R, Logani S, Seidman JD, Shih IM. Am J Surg Pathol. 2009 May 20. PMID: 19461510

- Vang R, Shih IM, Salani R, Sugar E, Ayhan A, Kurman RJ. Subdividing Ovarian and Peritoneal Serous Carcinoma Into Moderately Differentiated and Poorly Differentiated Does not Have Biologic Validity Based on Molecular Genetic and In Vitro Drug Resistance Data. Am J Surg Pathol. 2008 Aug 30. PMID: 18769340

- Yemelyanova A, Mao TL, Nakayama N, Shih IM, Kurman RJ. Low-grade Serous Carcinoma of the Ovary Displaying a Macropapillary Pattern of Invasion. Am J Surg Pathol. 2008 Sep 5. PMID: 18779727

- Kim SW, Kim JW, Kim YT, Kim JH, Kim S, Yoon BS, Nam EJ, Kim HY. Analysis of chromosomal changes in serous ovarian carcinoma using high-resolution array comparative genomic hybridization: Potential predictive markers of chemoresistant disease. Genes Chromosomes Cancer. 2007 Jan;46(1):1-9. PMID: 17044060

- Staebler A, Karberg B, Behm J, Kuhlmann P, Neubert U, Schmidt H, Korsching E, Burger H, Lelle R, Kiesel L, Bocker W, Shih IeM, Buchweitz O. Chromosomal losses of regions on 5q and lack of high-level amplifications at 8q24 are associated with favorable prognosis for ovarian serous carcinoma. Genes Chromosomes Cancer. 2006 Oct;45(10):905-17. PMID: 16845658