1.TP53 variants in p53 signatures and the clonality of STICs in RRSO samples
Tomoko AKAHANE ; 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
Journal of Gynecologic Oncology 2022;33(4):e50-
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.
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