Eda Kayali

Advanced stage, elevated mFIB-4 score, and MMR gene loss as independent predictors of oncological outcomes in endometrioid endometrial cancer: A retrospective observational study

This study aimed to evaluate the association between noninvasive liver fibrosis and steatosis scores (including the aspartate transaminase to alanine transaminase ratio to platelet ratio index, aspartate transaminase-platelet ratio index [APRI], Fibrosis-4 index, modified Fibrosis-4 index [mFIB-4], and hepatic steatosis index) as well as ultrasonographic steatosis scores (USS), with histopathological features of endometrioid-type endometrial cancer (EC) and their potential impact on survival outcomes. This retrospective observational study included 415 patients diagnosed with endometrioid-type EC who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Preoperative metabolic scores, including aspartate transaminase to alanine transaminase ratio to platelet ratio index, APRI, Fibrosis-4 index, mFIB-4, and hepatic steatosis index, were calculated from blood samples. USS and the diagnosis of metabolic dysfunction-associated fatty liver disease were based on liver imaging and metabolic criteria. Disease-free survival and overall survival were analyzed; significance was set at P  < .05. Analysis showed that patients with body mass index <30 kg/m 2 had higher rates of deep myometrial invasion (44.8% vs 27.3%, P  = .014), serosal invasion (6.9% vs 0.6%, P  = .017), lympho-vascular space invasion (34.5% vs 15.8%, P  = .002), and MSH6 loss (9.8% vs 1.4%, P  = .014) compared to obese patients. USS correlated with age, myometrial invasion depth, and PMS2 loss. Myometrial invasion >1/2 was more frequent in patients with mFIB-4 > 0.19 (37.5% vs 29%, P  = .048). Lower APRI (≤0.19) was related to the higher rate of cervical stromal invasion (15.8% vs 9.1%, P  = .027), lympho-vascular space invasion (29.7% vs 17.7%, P  = .002), adnexal involvement (11.3% vs 5.6%, P  = .026), and lymph node metastasis (24.1% vs 12.8%, P  = .009). Multivariable analysis showed advanced stage (HR = 5.172, P  < .001) and presence of at least one mismatch repair gene defect (HR = 2.936, P  = .011) independently predicted poor disease-free survival. Advanced stage (HR = 7.519, P  < .001) and a high mFIB-4 score (HR = 2.281, P  = .020) independently predicted worse overall survival. In conclusion, advanced stage remains the most significant independent predictor of poor oncological outcomes in endometrioid-type EC. Furthermore, this study highlights the prognostic relevance of metabolic dysfunction in this patient group. Noninvasive liver fibrosis markers (particularly mFIB-4 and APRI) were significantly associated with adverse histopathological features and survival outcomes, suggesting their potential role in risk stratification and prognosis assessment in endometrioid-type EC.

Nicotinamide Phosphoribosyltransferase (NAMPT) as a New Marker in Cervical Preinvasive Lesions

Objective To examine the relationship between cervical dysplasia and tissue levels of nicotinamide phosphoribosyltransferase (NAMPT). Materials and Methods Patients who underwent colposcopic biopsy due to human papilloma virus positivity were classified as normal tissue and cervical intraepithelial neoplasia (CIN) 1, CIN 2-3. These were stained with NAMPT antibodies using streptavidin-biotin peroxidase method (Invitrogen, 85-9043, CA, USA). The staining intensity was scored as: 0, 1, 2, and 3 for no, mild, moderate, and intense staining, respectively. The percentage score was classified as: 1, 2, and 3 for 1% to 33%, 34% to 66%, and 67% to 100% positivity, respectively. The product score was calculated. Totally, 86 patients were included in the study. Results The NAMPT staining scores were significantly higher in the CIN 2-3 group compared to the group with CIN 1/normal (90% vs 9%; respectively, P  < .000). No intense NAMPT staining was observed in any of the specimens with CIN 1 or normal results. The percentage score of 2 to 3 was seen in 83% and 12% for patients with and without CIN 2-3, respectively ( P  < .000). Using a cutoff value for product score of 2, the test demonstrated a sensitivity, a negative-predictive value, a specificity, and a positive-predictive value of 96%, 98%, 80%, and 71%, respectively. Although the product score was 2 and higher for 96% of CIN 2-3 specimens, 78% of those with CIN 1 or normal results had that below 2. Conclusion The NAMPT staining differs significantly among groups and may be a useful marker for distinguishing CIN 2-3 from normal tissue and CIN 1. That has potential to improve the sensitivity–specificity of diagnosing and treating cervical premalignant lesions.