Aysegul Yucel Polat

MiR-25 and KLF4 relationship has early prognostic significance in the development of cervical cancer

Cervical squamous cell carcinoma (SCC) is one of the common cancer types among women. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the formation and development of many cancer types by regulating expression of their targets. While many studies have investigated the relationship between miRNAs and cervical cancer, no robust miRNA biomarkers have been defined yet for diagnosis of cervical lesions. In this study, we performed a statistical meta-analysis to identify miRNAs and a class compassion analysis to evaluate mRNAs with the power to discriminate between normal, intraepithelial lesions and invasive cancer samples. Differentially expressed (DE) mRNAs were compared with the targets of meta-miRNAs. After bioinfomatics analysis and qRT-PCR validations with cytology samples and FFPE tissues, we defined miR-25 and its target KLF4 (Kruppel-like factor 4) as candidate biomarkers for in vitro studies. Our results showed that miR-25 expression was significantly higher in precancerous lesions and invasive carcinoma while presenting consistent expression patterns in both cytological and FFPE tissue samples. In line with this, its direct target KLF4 expression decreased in precancerous lesions in cytological samples and also in the invasive cancer group in FFPE tissues. Furthermore, in vitro studies showed that mir-25 inhibition decreased proliferation and motility of HeLa cells and promoted an increase in the protein level of KLF4. We conclude that inhibition of miR-25 may upregulate KLF4 expression and regulate cell proliferation and motility in cervical cancer.

Atypical glandular cells in Papanicolaou test: Which is more important in the detection of malignancy, architectural or nuclear features?

AbstractObjectiveAtypical glandular cells (AGCs) in Pap (Papanicolaou) smears are uncommon but may represent various benign and malignant lesions. The aim of this study was to evaluate the AGC incidence in Pap smears, analyse the relationship between AGC and malignancy, and reveal the importance of architectural and nuclear features observed cytologically in malignancies.MethodsPatients diagnosed with AGC on the basis of cervicovaginal cytology between May 2011 and July 2018 were included in this study. All slides were retrospectively reviewed and subclassified according to the Bethesda 2001 classification system. The cytomorphological features observed in the smears were recorded. Cytohistological correlations were evaluated, and the significant clinicopathological findings for malignancy were determined.ResultsOf 87 536 Pap smears, 195 (0.22%) had AGC results and 156 had tissue follow‐up. Among the 156 smears with AGC, 80 (51.3%) were diagnosed as AGC‐NOS (atypical glandular cells, not otherwise specified) and 76 (48.7%) as AGC‐FN (atypical glandular cells, favour neoplastic). Follow‐up biopsies revealed benign pathologies in 49 cases (31.4%) and malignant pathologies in 107 (68.6%). The rate of malignancy observed in AGC‐FN cases (89.5%) was higher than the rate of malignancy in AGC‐NOS cases (48.8%). Among the cytomorphological features, nuclear irregularity, presence of macronucleoli, feathering, loss of polarity, papillary pattern, and three‐dimensional formation were found to be significant indicators of malignancy.ConclusionAs AGC in Pap smear was associated with a clinically significant diagnosis in 68.6% of the cases in our study, we suggest that all patients with AGC should undergo further clinical assessment.