TP53 variants in p53 signatures and the clonality of STICs in RRSO samples
- Author:
Tomoko AKAHANE
1
;
Kenta MASUDA
;
Akira HIRASAWA
;
Yusuke KOBAYASHI
;
Arisa UEKI
;
Miho KAWAIDA
;
Kumiko MISU
;
Kohei NAKAMURA
;
Shimpei NAGAI
;
Tatsuyuki CHIYODA
;
Wataru YAMAGAMI
;
Shigenori HAYASHI
;
Fumio KATAOKA
;
Kouji BANNO
;
Kokichi SUGANO
;
Hajime OKITA
;
Kenjiro KOSAKI
;
Hiroshi NISHIHARA
;
Daisuke AOKI
Author Information
- Publication Type:Original Article
- From:Journal of Gynecologic Oncology 2022;33(4):e50-
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objective:Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.
Methods:We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.
Results:TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.
Conclusion:The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.
