Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb 9;34(1):6.
doi: 10.1186/s43046-022-00104-9.

Subtyping of high grade serous ovarian carcinoma: histopathological and immunohistochemical approach

Marwa Khashaba  1 , Mohamed Fawzy  2 , Azza Abdel-Aziz  2 , Ghada Eladawei  2 , Reham Nagib  3
Affiliations

Subtyping of high grade serous ovarian carcinoma: histopathological and immunohistochemical approach

Marwa Khashaba et al. J Egypt Natl Canc Inst. .

Abstract

Background: High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested different prognosis. Addressing the presence of histopathological and immunohistochemical differences in HGSOC that parallel the molecular subtypes can help in tailoring the management protocol to improve therapeutic response and patient outcome.

Methods: This retrospective study was conducted on 85 specimens for cases of HGSOC. Cases were classified according to histopathological findings into mesenchymal, proliferative, immunoreactive, and differentiated subtypes. Cases were immunostained with ER, PR, Ki67, CD8, E-cadherin, and vimentin.

Results: By applying histopathological data, cases were subdivided into 4 groups; mesenchymal type represented by 25 cases, proliferative type which included 14 cases, the immunoreactive type included 14 cases, and differentiated type represented by 32 cases; 13 of them had SET features and 19 had papillary architectural features. A significant correlation was found between Ki67 and proliferative subtype, as well as between CD8 and immunoreactive subtype. ER showed significantly higher expression in proliferative subtype in the group treated by primary debulking. CD8 showed a significant correlation with solid endometroid transitional (SET) pattern in the group that underwent interval debulking. In terms of prognosis, the shortest median progression-free survival (PFS) was for mesenchymal subtype, while the longest median PFS was for differentiated subtype with SET architectural pattern with statistically significant correlation. No correlation was found between any of the studied parameters and overall survival.

Conclusion: Histopathological features and immunohistochemistry can help to stratify HGSOC into prognostic distinct groups.

Keywords: Immunoreactive; Mesenchymal; Papillary serous carcinoma; Prognosis; Proliferative.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
An algorithm for histopathological classification of cases of HGSC
Fig. 2
Fig. 2
x400 A H&E photomicrograph of mesenchymal subtype of HGSC where cellular stroma around tumor sheets is seen. B Negative E-cadherin expression in same tumor type
Fig. 3
Fig. 3
x400 A H&E photomicrograph of proliferative subtype of HGSC showing frequent mitotic figures. B Nuclear expression of Ki67 in > 25% of tumor cell nuclei. C Diffuse strong nuclear expression of ER in the same case
Fig. 4
Fig. 4
x400 A H&E photomicrograph of immunoreactive subtype of HGSC, lymphocyte-infiltrating tumor nests >20 /HPF. B These lymphocytes are highlighted by CD8
Fig. 5
Fig. 5
A H&E. Photomicrograph of differentiated subtype of HGSC formed of papillary structures (x200). B H&E. Photomicrograph of differentiated subtype of HGSC with SET pattern (x200). C CD8 highlighting intratumoral lymphocytes between the sheets of HGSC with a SET pattern
Fig. 6
Fig. 6
The histopathological type is a significant factor for PFS. P=0.008
Fig. 7
Fig. 7
Immunohistochemical markers significantly associated with PFS
See this image and copyright information in PMC

References

    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–2917. doi: 10.1002/ijc.25516. - DOI - PubMed
    1. Cheng WS, Chiang JH. Analysis of Prognostic Marker Panel for High-Grade Serous Ovarian Cancer through Age-Dependent DNA Methylation. J Phylogen Evolution Biol. 3:153. 10.4172/2329-9002.1000153 Page 2 of 7 with ovarian cancer and tumor growth, as reported in the literature (Doctoral dissertation. These results also indicated that our method reliably extracted age-dependent markers with the potential to consider further clinical testing).
    1. Verhaak RG, Tamayo P, Yang JY, Hubbard D, Zhang H, Creighton CJ, et al. Prognostically relevant gene signatures of high-grade serous ovarian carcinoma. J Clin Invest. 2012;123(1):517–25. - PMC - PubMed
    1. Konecny GE, Wang C, Hamidi H, Winterhoff B, Kalli KR, Dering J, et al. Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer. JNCI: J Natl Cancer Institute. 2014;106(10). - PMC - PubMed
    1. Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 2008;14(16):5198–5208. doi: 10.1158/1078-0432.CCR-08-0196. - DOI - PubMed