Fig 1.
Study flowchart: All women were invited to participate in diagnosis of AGC with a methylation biomarker study.
Physician-directed sampling was performed with a cytobrush (CooperSurgical, Inc.). Patients with Pap smear of AGC underwent colposcopy and cervical biopsy, endometrial sampling, or conization in accordance with treatment guidelines. CIN III/CIS and complex hyperplasia of the endometrium were taken as cutoff criteria for QMS-PCR of seven genes. The receiver operating characteristic (ROC) curve was used to select the optimal cutoff value for the methylation level of each gene. Methylation levels that were higher than the threshold were classified as “high methylation”, whereas those that were lower than the threshold were recorded as “low methylation”.
Table 1.
Pathology and HPV results of AGC patients.
Fig 2.
Methylation index (meth-index) on a log scale of methylated (m) SOX1m, PAX m, ZNF582 m, PTPRR m,AJAP1m, HS3ST2m, and POU4F3m levels from scrapings of the normal cervix and tumors graded as CIN1, CIN2, CIN3, CIS, or SCC/AC, or endometrial lesions (including simple hyperplasia and complex hyperplasia of the endometrium) by histopathology.
Each dot represents the testing result of one patient.
Table 2.
Clinical performance of methylation biomarker and HPV to detect CIN3+ /CIS and complex hyperplasia of endometrium in AGC.
Table 3.
Summary of clinical performance of methylation biomarker, HPV and CA-IX.
Fig 3.
Proposed algorithm for management of AGC in TGOG study.
For women with cytology identifying AGC, methylation biomarkers of SOX1 and POU4F3 are recommended. If, after a comprehensive examination, women with positive SOX1m and POU4F3m have no recognizable disease, a cervical conization or an endometrial sampling may be considered, otherwise, repeat cytology 3 months later should be the preferred recommendation because the sensitivity of SOX1 and POU4F3 is 100%.