PMC7670051_01
Pathological findings. (A) H&E staining demonstrated the presence of both serous and endometrioid components. Immunohistochemistry staining of MSH2 (B) and MSH6 (C) (100x magnification).
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F1
IIIA serous papillary adenocarcinoma mixed with endometrioid carcinoma with squamous differentiation (~70% for serous carcinoma component and 30% for endometroid carcinoma component, respectively) (Figure 1A), with tumor metastasis to both fallopian tubes. Immunohistochemistry analysis showed loss of MSH2 (Figure 1B) and MSH6 (Figure 1C) protein expression in the EEC component. CA125 level increased to 231.6 U/ml. CT scan suggested an enlarged left para-aortic lymph node (37*30 mm) (Supplementary Figures 1A,E). Partial remission was achieved at 9 weeks after treatment with the shrinkage of an enlarged left para-aortic lymph node (Supplementary Figures 1B,F). CA125 (12.28 U/ml) was observed after 2 months of treatment. CT scan at 15 weeks after treatment demonstrated continuous shrinkage of the enlarged lymph node (Supplementary Figures 1C,G). Fortunately, the CT scan did not reveal progression as a result of drug interruption (Supplementary Figures 1D,H).
Family pedigree and germline mutations identified in the index patient. (A) Family pedigree. The index patient is indicated with an arrow, and the circle filled with black color denotes endometrial cancer. (B) Visualized sequencing data shows the BRCA1 variant. MSH2 exons coverage depth analysis in the index patient (C) and another sample with the same batch (D).
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F2
BRCA1 (NM_007294.3 c.3348_3351delAGTT p.V1117Rfs*11) and MSH2 (large deletion of exons 4-16) were identified (Figures 2B-D). Besides, a total of 72 somatic mutations were detected, including putative or known functional mutations in PTEN, ARID1A, TP53, FBXW7, and KRAS (Supplementary Table 1). Unfortunately, her son harbors both the BRCA1 and MSH2 mutations (Figures 2A, Supplementary Figures 2, 3).