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.
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)
Grades
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).
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)
Variants
macropapillary pattern of invasion (18779727)
invasive micropapillary serous carcinoma (MPSC)
CGH
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
- 3q amplification (16845658)
- 8q amplification (16845658)
- 19p amplification (16845658)
- 19q amplification (16845658)
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 adenocarcinomas
References
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
