PMC8636970_01
Timeline of treatment with radiography of responses and CA125 concentration. (A) Timeline of treatment and corresponding MRI. (B) Timeline of treatment and corresponding CA125 concentration.
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A 63-year-old, female new patient was admitted to the hospital in October 2012, and the timeline of her clinical records and treatments throughout the 9-year course are demonstrated in Figure 1. March 2020, November 2020, and March 2021 all confirmed progressive shrinkage of retroperitoneal lymph nodes (Figure 1A). Molecularly, we detected one ClinVar database-defined "likely pathogenic" somatic mutation S241C in tumor suppressor TP53 at a mutant allele frequency of 2.97% from the November 2019 NGS test (Table S2).
Imaging examinations during the treatment. (A) MRI and PET-CT evaluation at the time of the patient's initial admission in October 2012. (B) H&E and IHC staining in October 2012. The p40-positive cells are pointed by the red triangles. (C) MRI evaluation in July 2017 and PET-CT evaluation in May 2019. (D) H&E and IHC staining in November 2019. Scale bars represent 200 microm.
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The patient presented with an egg-sized lump in her left iliac fossa (Figure 2A, left). The patient underwent resection of the lump, and the pathological results (Figure 2B) are as follows: Haemotoxylin and eosin (H&E) staining revealed the histologic pattern of adenocarcinoma. Subsequent positron emission tomography-computed tomography (PET-CT) examinations (Figure 2A, right) revealed increased fluorodeoxyglucose (FDG) metabolism in the right sterno-diaphragmatic angle and cardiophrenic angle, right crus of the diaphragm, retroperitoneum, and left pelvic cavity, which was initially considered as metastatic tumors. In July 2017, the CA125 level increased to 824.2 U/mL, and magnetic resonance imaging (MRI) indicated enlarged lymph nodes in the retroperitoneal area (Figure 2C, left). In May 2019, the patient underwent the PET-CT examination (Figure 2C, right), which revealed multiple retroperitoneal lymph nodes with high FDG metabolism, suggestive of metastasis. In November 2019, she received the CT-guided retroperitoneal lymph node puncture operation, and the pathological results of the lymph node biopsy are as follows (Figure 2D).
Diagrams of mutations identified in NGS testing. (A) Schematic diagram of the R71K mutation in full-length BRCA1 (adopted from cBioPortal MutationMapper https://www.cbioportal.org/mutation_mapper, retrieved on Nov. 3, 2021). (B) Abundance change of TP53 S241C in the time course of olaparib treatment. The ctDNA abundance measured by each NGS test is represented by the dot.
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The NGS test revealed a pathogenic, heterozygous germline BRCA1 331G>A nucleotide substitution mutation, which results in an Arg-to-Lys change (Figure 3A). With olaparib treatment, we observed effective elimination of ctDNA as the TP53 S241C mutation was no longer detected in the two subsequent NGS tests (Figure 3B).