Background: DNA methylation is an essential factor in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer. The aim was to investigate the diagnostic value provided by methylation biomarkers of six tumor suppressor genes (ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671) for cervical precancerous lesions and cervical cancer. Methods: The histological cervical specimens of 396 cases including 93 CIN1, 99 CIN2, 93 CIN3 and 111 cervical cancers were tested for methylation-specific PCR assay (GynTect®) of score and positive rate. Among them, 66 CIN1, 93 CIN2, 87 CIN3 and 72 cervical cancers were further used for paired analysis. A chi-square test was used to analyze the difference of methylation score and positive rate in cervical specimens. The paired t-test and paired chi-square test were for analyzing the methylation score and positive rate in paired CIN and cervical cancer cases. The specificity, sensitivity, odds ratio (OR) and 95% confidence interval (95% CI) of the GynTect® assay for CIN2 or worse (CIN2 +) and CIN3 or worse (CIN3 +) were evaluated. Results: According to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P = 0.000). The methylation score above 1.1 was more common in CIN2 + than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P = 0.033, 0.000 and 0.000, respectively), except for CIN2 (P = 0.171). While the positive rate of GynTect® in each paired group had no difference (all P > 0.05). The positive rate of every methylation marker in the GynTect® assay showed differences in four cervical lesion groups (all P < 0.05). The specificity of GynTect® assay for detection of CIN2 + /CIN3 + were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect®/ZNF671 were significantly higher in CIN2 + : odds ratio (OR) 5.271/OR 13.909, and in CIN3 + : OR 11.022/OR 39.150, (all P < 0.001). Conclusion: The promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect® assay based on cervical specimens provides diagnostic values for detecting CIN2 + and CIN3 + .
Aims: To explore the expression of secretagogin (SCGN) in neuroendocrine carcinoma of the uterine cervix and analyse its relationship with clinicopathological characteristics and prognosis. Methods: From January 2010 to December 2017, 44 patients with cervical neuroendocrine carcinoma undergoing surgery were included in the study group, and 55 patients with cervical non-neuroendocrine carcinoma (including 30 cases of cervical squamous cell carcinoma and 25 cases of cervical adenocarcinoma) undergoing surgery were included in the control group. Immunohistochemical staining of SCGN was performed in both groups and compared with three common neuroendocrine markers, chromogranin A, synaptophysin (Syn) and CD56 in the study group. Detailed clinicopathological data of the two groups were analysed, and the patient survival in the study group was followed up. Results: The positive expression of SCGN in cervical neuroendocrine carcinoma, cervical adenocarcinoma and squamous cell carcinoma was 65.9% (29/44), 8% (2/25) and 0%, respectively. The positive expression of SCGN in cervical neuroendocrine carcinoma was significantly higher than that in cervical adenocarcinoma and squamous cell carcinoma (χ 2 =44.5, p0.05 for all). The intensity of SCGN staining in patients with cervical neuroendocrine carcinoma with lymph node metastasis was significantly higher than that in patients without lymph node metastasis (p=0.020). However, there was no significant association between SCGN expression and survival among patients with cervical neuroendocrine carcinoma (p=0.633). Conclusions: SCGN is a new neuroendocrine marker for cervical neuroendocrine carcinoma, whose expression correlates with lymph node metastasis.
Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a highly invasive cervical cancer. The immunohistochemical criteria is an important aspect for assistant diagnosis of SCNECC. However, which markers can be appropriate selection for diagnosing SCNECC were not determined. The aim was to systematically evaluate expression levels of four neuroendocrine markers (containing synaptophysin (Syn), neural cell adhesion molecules (CD56), neuron-specific enolase (NSE) and chromograninA (CgA)) and to find out the appropriate selection for diagnosing SCNECC. Four English and three Chinese libraries were retrieved between 1984 and 2020. 23 studies about NSE, 36 studies about Syn, 23 studies about CD56 and 36 studies about CgA (all studies containing 581 patients) were eligible for meta-analyses. The pooled positive expression percentages (95% CI; I2) were as follows: 84.84% (79.41–90.27%; 76.7%) for Syn, 84.53% (79.43–89.96%; 37.5%) for CD56, 77.94% (69.13–86.76%; 83.5%) for NSE, and 72.90% (67.40–78.86%; 59.7%) for CgA. The positive proportions (95% CI; I2) ranked top three of simultaneous expressions of two markers were 87.75% (82.03–93.87%, 33.3%) for Syn and CD56, 70.92% (50.50–87.68%, 82.7%) for Syn and NSE, 65.65% (53.33–76.98%, 73.5%) for Syn and CgA. This confirms that Syn and CD56 are reliable indicators for diagnosing SCNECC.
Background: We assessed the image quality of endometrial cancer lesions by readout segmentation of long variable echo-trains (RESOLVE) diffusion-weighted imaging (DWI) compared with that by single-shot echo-planar imaging (SS-EPI) DWI, aimed to explore the value of RESOLVE DWI for determining myometrial invasion and clinical stage in endometrial cancer. Materials and methods: From April 2017 to March 2018, a total of 30 endometrial cancer patients (mean age 52.8 ± 9.0 years), who had undergone RESOLVE DWI and SS-EPI DWI, were included in the study. The image quality of endometrial carcinoma by two kinds of DWI scanning methods was compared qualitatively and quantitatively. The Spearman rank correlation test was used to assess the correlation of qualitative image quality scores between two readers. The accuracy of two DWI methods in detecting myometrial invasion and staging of endometrial carcinoma was calculated according to postoperative pathological results. The indexes were analyzed including sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). Results: The qualitative score of RESOLVE DWI group was superior to SS-EPI DWI group in every aspect of five aspects (all P < 0.001). Interobserver agreement of depiction was good or excellent in two DWI sequences. Signal to noise ratio and contrast to noise ratio values in RESOLVE DWI group were both higher than those in SS-EPI DWI group (P<0.001). No statistical difference of apparent diffusion coefficient value was observed between two DWI groups (P = 0.261). The specificity, accuracy, PPV, and NPV of estimating myometrial invasion by RESOLVE DWI in three cases (intramucosal lesion, <50% superficial invasion and ≥ 50% deep invasion) were all higher than those by SS-EPI DWI for endometrial carcinoma. Especially RESOLVE DWI was valuable in judging <50% superficial invasion (95%CI:0.586, 0.970). No significant difference in accuracy staging was between the two DWI groups (P = 0.125). Conclusion: RESOLVE DWI can provide higher quality images of endometrial carcinoma than SS-EPI DWI. The high-quality images are helpful for precise assessment of myometrial invasion in endometrial cancer.