The oncologic outcomes of endometrial cancer metastasizing to the adrenal gland and kidney: from case to analysis.

Objective: To evaluate the oncologic outcomes of endometrial cancer metastasis to the adrenal gland and kidney, based on a case study and review of the literature. Material and Methods: A systematic review of the medical literature was performed to identify articles about metastatic endometrial cancer to the adrenal gland and kidney from 1975 until 2021. Results: A 55-year-old female patient was admitted to our center. On pelvic examination, a mass protruding out of the cervix was observed, which was shown to be endometrioid carcinoma on biopsy. Disease stage was IVB, based on radiological and pathological results and the International Federation of Gynecology and Obstetrics 2018 staging. Neo-adjuvant chemotherapy was given. After therapy, the patient underwent type 2 hysterectomy, bilateral salpingo-oophorectomy, total omentectomy and lymph node dissection. Left nephrectomy, left adrenalectomy and left hemicolectomy were also performed because the conglomerate tumor invaded the left kidney, left adrenal gland, and left colon mesentery. Pathological findings were consistent with metastasis of endometrioid carcinoma in the left adrenal gland, left kidney parenchyma and hilum. Conclusion: Metastasis of endometrial cancer to the adrenal gland and kidney is extremely rare and metastasis to the kidney has been reported in only two previous cases. When there is an intraperitoneal spread of endometrial cancer, as well as ovarian cancer, cytoreductive surgery without leaving a residual tumor should be undertaken andshould include adrenalectomy and nephrectomy, if necessary.

Serum and Follicular Fluid Thiol/Disulfide Homeostasis in Diminished Ovarian Reserve Patients Undergoing In Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

INTRODUCTION: The etiologies of diminished ovarian reserve (DOR) are still poorly understood, and many factors such as age, autoimmunity, genetics, idiopathicity, iatrogenesis, and oxidative stress (OS) play a role. Oxidative cellular damage increases following reactive oxygen species (ROS)-induced aging. This is the first study to evaluate the serum and follicular fluid (FF) thiol/disulfide homeostasis in patients under 35 years of age with DOR undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: In this study, DOR was defined by the Poseidon criteria, and Poseidon group 3 women were selected as the study group (n = 40). The control group was composed of patients with the diagnosis of mild-moderate male factor infertility (n = 30). RESULTS: The FF and serum native and total thiol levels, the markers of the antioxidant system, were significantly decreased in the DOR group compared with the control group (p = 0.021) (p = 0.037) (p = 0.029) (p = 0.04). On the other hand, we found no significant differences in the oxidant parameters between the groups (p > 0.05). CONCLUSIONS: An intrinsic deficiency of antioxidants can play an important role in the etiology of DOR. The dietary addition of antioxidants could be beneficial in DOR patients.

Evaluation of Dysfunctional HDL by Myeloperoxidase/Paraoxonase Ratio in Unexplained Infertility Patients Undergoing IVF/ICSI.

The relationship between oxidative stress and unexplained infertility (UEI) has not been studied in detail. This is the first study to evaluate dysfunctional high-density lipoprotein (HDL) by the myeloperoxidase (MPO) and paraoxonase (PON) ratio to investigate the role of oxidative stress in UEI. MATERIALS AND METHODS: Patients with UEI (study group, n = 40) and male factor infertility (control group, n = 36) were included in this prospective study. Demographics and laboratory assessments were analyzed. RESULTS: Total dosages of gonadotropin were higher in UEI when compared to the control group (p = 0.033). Number of Grade 1 embryos and the quality of blastocysts were lower in UEI than in the control group (p = 0.024, p = 0.020, respectively), whereas serum MPO/PON ratio was higher in UEI (p = 0.042). Stepwise linear regression analysis revealed that serum MPO/PON ratio levels could significantly predict the duration of infertility (p = 0.012). CONCLUSIONS: Serum MPO/PON ratio increased in patients with UEI, whereas the number of Grade 1 embryos and the quality of blastocysts decreased. Similar clinical pregnacy rates were found in both groups but the ET on day five is associated with higher clinical pregnancy rate in the male factor infertility.

Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears.

OBJECTIVE: The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC-NOS). METHODS: We retrospectively reviewed Pap smear tests that resulted as AGC-NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC-NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed. RESULTS: Two hundred fifty-four patients with AGC-NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively. CONCLUSIONS: Patients diagnosed with AGC-NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC-NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.

Post-recurrence survival analysis of patients with pulmonary recurrence from gynaecologic cancers: a multi-institutional analysis of 122 patients.

In this retrospective study, patients with epithelial gynaecologic cancer with pulmonary recurrence (PR) were evaluated from five national gynaecologic oncology clinics. Patients with a diagnosis of primary endometrial, ovarian/fallopian tube/peritoneal, cervical or vaginal/vulvar tumours who developed an initial PR were included in the study A total of 122 patients were included in the study. The median follow-up time after recurrence was 7.5 (range, 1-84) months. The 2-year PRS was 48% in the main cohort. The risk of death was more than seven times higher in patients who did not receive salvage chemotherapy compared with those who did (hazard ratio: 7.6, 95% CI: 3.0-18.9; p < .001). When squamous cell carcinoma was compared with the other tumour types, the risk of death increased more than three times (hazard ratio: 3.7, 95% CI: 1.4-9.6; p = .007).IMPACT STATEMENTWhat is already known on this subject? Pulmonary recurrence (PR) from gynaecologic malignancies is rare and can cause major clinical problem. Therefore, defining the clinical and pathologic characteristics and recurrence patterns are essential.What the results of this study add? This study demonstrates non-squamous subtype and salvage chemotherapy at PR were associated with improved survival.What of these findings for clinical practice and/or further research? To the best of our knowledge, our study is the largest study to investigate the clinico-pathologic characteristics, recurrence patterns, treatment options, and post-recurrence survival (PRS) in patients with PR from epithelial gynaecologic cancers. Future research should examine the underlying causes of these findings.

Prognostic value of systemic inflammatory response markers in cervical cancer.

We investigated the association between preoperative ratios of inflammatory markers and the prognosis in patients with invasive cervical cancer (CC). In this single-centre study, we retrospectively enrolled 163 CC patients who underwent radical hysterectomy between February 2008 and October 2018. Among the evaluated ratios, a high neutrophil-to-lymphocyte ratio (N/L) was significantly associated with deep stromal invasion and tumour size larger than 2 cm, whereas a high M/L was significantly related to advanced-stage CC (IB3-IIIC2), lymphatic metastasis (total) and pelvic lymph node metastasis (p= .002, p= .046 and p= .046, respectively). The neutrophil count plus monocyte-to-lymphocyte ratio (NM/L) and platelet-to-lymphocyte ratio (P/L) were significantly higher in patients with deep stromal invasion, advanced stage and tumour size larger than 2 cm (p=.01, p=.044 and p=.007; p=.004, p=.005 and p=.003, respectively). In the multivariate analysis, high NM/L (>168) was associated with a statistically significant hazard ratio of 3.04 (95% CI: (1.38-6.72); p=.006) for recurrence and 9.05 (95% CI: (2.10-38.99); p=.003) for death. Both stage and NM/L are independent prognostic factors that are significantly associated with recurrence and overall survival in CC.Impact StatementWhat is already known on this subject? Previous studies suggested that there is a relationship between inflammation and the formation, development and progression of cancer. However, the relationship between cervical cancer (CC) and inflammatory blood parameters is incompletely understood.What do the results of this study add? This study investigated the relationship between systemic blood inflammatory ratios and clinicopathological patient characteristics and disease outcomes in CC.What are the implications of these findings for clinical practice and/or further research? According to this study, systemic blood inflammatory ratios may help predict the prognosis and survival of patients with CC.

Nicotinamide N-methyltransferase expression in squamous cell carcinoma of the vulva.

The molecular pathways involved in the development of vulvar squamous cell carcinoma (SCC) cancer are not completely known. Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme associated with tumorigenesis and metastasis in a variety of cancers. Its role in vulvar cancer has not been studied, previously. Vulvar SCC, high and low grade squamous intraepithelial lesions (SILs) and benign squamous hyperplasia were analysed immunohistochemically. The mean staining score for vulvar SCC was significantly higher than the score for vulvar squamous hyperplasia (p<.001). The mean relapse-free survival for patients with low and high NNMT expression was 41.4 months (95% CI: 25.6-57.2) and 19.8 months (95% CI: 3.0-36.6), respectively (p=.035). The mean disease-specific survival for patients with low and high NNMT expression was 75.8 months (95% CI: 57.5-94.2) and 27.8 months (95% CI 12.2-43.4), respectively (p=.015). Although quite preliminary, this study showed that NNMT expression was elevated in vulvar SCC compared to benign and premalignant lesions. Additionally, elevated NNMT expression was associated with poor survival. Impact StatementWhat is already known on this subject? Nicotinamide N-methyltransferase (NNMT) is a methyltransferase, associated with tumour progression, spread and poor prognosis in a variety of cancers. Its upregulation can lead to DNA hypomethylation, which can in turn result in the activation of proto-oncogenes and deactivation of tumour suppressor genes.What do the results of this study add? Although quite preliminary, this study showed that NNMT expression was elevated in vulvar SCC compared to benign and premalignant lesions. Additionally, elevated NNMT expression was associated with poor survival.What are the implications of these findings for clinical practice and/or further research? NNMT has been regarded as a potential target of cancer therapy and its role in vulvar cancer has not been studied, previously. This is the first study to investigate the expression of NNMT in vulvar cancer and associate NNMT elevation with poor survival. NNMT can further be investigated as a possible target of vulvar cancer therapy.

Incidence of unexpected leiomyosarcoma in a Turkish province: a retrospective multi-centre study in a low income setting.

The aim of the current study was to estimate the incidence of unexpected leiomyosarcoma (LMS) in patients who underwent surgery due to leiomyomas in Konya province, and to contribute to the literature discussing comparisons with similar studies. The digital archives of eight high-volume hospitals were studied for surgeries performed due to leiomyomas between January 2012 and January 2019, and leiomyosarcoma incidence was calculated based on the data obtained. Twenty-one patients in 3703 cases were found to have unexpected leiomyosarcoma, which means we can expect one leiomyosarcoma in 176 (0.56%) surgeries. Six more malignant tumours were detected among the remaining cases. Thus, our study estimated the incidence of unexpected leiomyosarcoma as 1/176 (0.56%), which is higher than most of the studies in the literature justifying the debate started by the FDA in 2014. As the tumour biology is not yet clear, and the incidence of unexpected leiomyosarcoma tends to be so high, the key focus must be to try to detect uterine leiomyosarcomas preoperatively for robust patient care.IMPACT STATEMENTWhat is already known on this subject? The incidence of unexpected leiomyosarcoma varies widely from 1/498 to 1/8300 depending on the study method and the type of procedure, and there is still controversy, even after the FDA statement that led to a major restriction in laparoscopic surgeries due to concerns about inadvertent morcellation of leiomyosarcomas.What do the results of this study add? To the best of our knowledge, the current study found the highest incidence of unexpected leiomyosarcoma, and consequently a serious evaluation of all patients undergoing surgery due to leiomyomas preoperatively considering a leiomyosarcoma candidate is recommended.What are the implications of these findings for clinical practice and/or further research? Studies on tumour biology and novel markers must be supported for accurate preoperative diagnosis of leiomyosarcoma.

Is striae gravidarum a sign of spontaneous premature birth?

BACKGROUND: This study aimed to investigate the association of striae gravidarum (SG) and preterm delivery. MATERIAL AND METHODS: This prospective cross-sectional study was performed between November 2018 and February 2019. In addition to demographic variables, SG score of the abdomen, presence of striae on breasts, arms, hips, and thighs were recorded. Davey's scoring system was used to define the severity of SG in the abdomen by the same investigators. Patients with cervical dilatation of 6 cm or more were included in the preterm labor group. RESULTS: A total of 292 women were included in the study. Of these, 176 (60.3%) had no SG, 20 (6.8%) had mild SG, and 96 (32.9%) had severe SG. Davey's score was lower in the group of patients with preterm birth than in the term birth groups (p = .002). SG in the breasts was more common in the preterm labor group than in the term birth group (p = .007). Also, the presence of SG in the legs was less common in the preterm labor group than in the term birth group (p < .001). In a logistic regression model, stria in the breasts revealed most significant in preterm delivery. CONCLUSIONS: No difference was found in the pregnancy length in gestational weeks among groups of different SG severity. The Davey's score and the presence of striae in the legs and breasts were found different between the preterm and term birth groups, and the term birth subgroups.

Evaluation of peripheral nodal recurrence in patients with endometrial cancer

OBJECTIVE: To evaluate the clinico-pathological patient features, prognostic factors, treatment options and outcomes of peripheral nodal recurrence (PNR) of endometrial cancer (EC). MATERIAL AND METHODS: The data of nine patients with PNR of EC from two institutions were reviewed. The electronic literature was reviewed from 1972 to May 2018 to identify articles about PNR in EC. Finally, 42 cases were evaluated. RESULTS: Nineteen (45.2%) patients were initially diagnosed with either stage I or II disease, whereas 20 (47.7%) patients had stage III or IV disease while the stages were not reported in three (7.1%). PNR developed as the first recurrence in 40 (95.2%) patients and as the second recurrence in 2 (4.8%) patients. Isolated PNR appeared in 35 (83.3%). Seven (16.7%) had PNR coexisting with multiple other sites of tumoral involvement. In the entire cohort, the 5-year and 10-year post-recurrence survival (PRS) were both 78%. Only the presence of distant hematogenous metastasis concurrent with PNR was significantly related to poor PRS (p=0.005). Among patients with isolated PNR, those who had surgery had 30% greater 5-year PRS than those treated without surgery, but this difference was not significant (80% vs 50%; p>0.05). CONCLUSION: A concurrent distant hematogenous metastasis was the only factor related to poor survival. A wide range of therapies exists for PNR but none of the therapies appear to be more advantageous than another. However, surgery as a component of treatment can render a survival advantage for patients who have isolated PNR.

Comparison of weekly methotrexate regimen versus methotrexate folinic acid 8-day regimen for treatment of low-risk gestational trophoblastic neoplasia.

AIM: We aimed to compare weekly methotrexate (MTX) regimen and methotrexate-folinic acid (MTX-FA) 8-day regimen in the first line treatment of low-risk gestational trophoblastic neoplasia (GTN). METHODS: The study included 73 patients with low-risk GTN according to FIGO risk score (FIGO risk score < 7). All patients received either weekly MTX (30-50 mg/m2 intramuscular weekly) or MTX-FA 8-day (MTX 1 mg/kg IV on day 1, 3, 5, and 7, FA 15 mg orally on day 2, 4, 6, and 8 given 24 h after each MTX dose, every 14 days) regimens in the first-line treatment of low-risk GTN. The baseline clinicopathological characteristics and treatment outcomes were analyzed retrospectively. RESULTS: The median age of all patients was 29 (18-51) years, and the median FIGO risk score was 3 (1-6). Of the patients recruited, 53 received MTX-FA 8-day, and 20 had MTX weekly regimens. There was a significant difference between the two groups with respect to FIGO risk scores (3 [1-6] vs. 2 [1-5], p = 0.023, MTX-FA 8-day vs. MTX weekly, respectively). The complete response rate was significantly higher in MTX-FA 8-day group compared to MTX weekly group (83% [44/53] vs. 60% [12/20] p = 0.038). In univariate and multivariate regression analyses, only presence of lung metastasis was found to be an independent risk factor for treatment resistance (OR: 3.959, 95% CI 1.105-14.179, p = 0.035). CONCLUSION: MTX-FA 8-day regimen is more effective than weekly MTX regimen in the first line treatment of low-risk GTN including patients even with higher FIGO risk scores. Treatment resistance may develop especially in patients with lung metastasis.

Malignant struma ovarii: From case to analysis.

AIM: To evaluate the clinico-pathologic features, treatment options, prognostic factors, and survival outcomes of malignant struma ovarii based on a systematic literature review in association with our case study. METHODS: A systematic review of the medical literature was performed to identify articles about malignant struma ovarii from January 1983 until July 2020. We evaluated 178 cases. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) of the entire cohort was 72.5% and 91%, respectively. In univariate analysis, younger age (<43 years), whole strumal cyst diameter >95 mm, presence of a histologic type other than papillary classic-type thyroid carcinoma within the tumor and lymphovascular space invasion were related to poor PFS. Patients who received radioactive iodine ablation (RIA) before the treatment failure had significantly higher PFS than those who did not receive RIA (94.9% vs. 64.8%, p = 0.041, respectively). In univariate analysis, PFS was significantly higher in patients who underwent gynecologic surgery followed by thyroidectomy and RIA compared with those who had surgical treatment only (94.5% vs. 64.3%, p = 0.05, respectively). However, this result could not be identified as an independent prognostic factor in multivariate analysis (p = 0.207). Younger age and absence of capsular involvement were related to significantly increased OS. Histologic type was the only independent prognostic factor for PFS (hazard ratio: 3.30, 95% confidence interval: 1.122-9.748; p = 0.030) CONCLUSION: The most common histologic subtype was the papillary classic type. The presence of a histologic type other than the classic papillary thyroid carcinoma within the tumor was an independent adverse prognostic factor.

Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells.

The anti-proliferative effects of 5-methylquinolinium (5MQ) of nicotinamide N-methyltransferase (NNMT) have not been previously investigated on a cervical cancer cell line. NNMT is a metabolic enzyme that is correlated with tumour progression and metastasis. 5MQ is a small molecule inhibitor of NNMT. 0.1-500 µM of 5MQ was tested on the HeLa epithelial cervical cancer cell line. Cell viability was assessed with the MTT test. TWIST, ZEB1, SERPIN1, SIRT1, CD16, mRNA and various protein expression levels were analysed with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively. 5MQ significantly inhibited HeLa cell proliferation in a concentration and time-dependent manner. Increased cell shrinkage, loss of cellular adhesions and apoptotic bodies were observed in HeLa cells after 5MQ treatment. Following treatment with 5MQ, ZEB1, SIRT1, CD16 mRNA levels were increased while TWIST and SERPIN1 mRNA levels were reduced. Expressions of oncogenic proteins phospho-Akt and SIRT1 were decreased. 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation.IMPACT STATEMENTWhat is already known on this subject? NNMT is a cytosolic enzyme involved in tumour progression, metastasis and treatment resistance. It was overexpressed in many human malignancies. 5-amino-1-methylquinolinium (5MQ) is a novel small molecule inhibitor of NNMT that has shown promising results in the treatment of obesity and in senescent muscle regeneration. 5MQ has not been tested on the HeLa cervical cancer cell line, previously.What do the results of this study add? In this study, 5MQ was tested on the HeLa cervical cancer cell line for the first time and the molecular changes associated with 5MQ treatment were analysed. 5MQ demonstrated significant anti-proliferative activity on HeLa cells, which displayed morphological signs of apoptosis. Treatment of HeLa cells with 5MQ led to an increase in ZEB1, SIRT1 mRNA while TWIST mRNA was decreased. Phospho-Akt and Sirtuin1 protein expressions were decreased.What are the implications of these findings for clinical practice and/or further research? 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation. 5MQ treatment was associated with a decrease in the expression of phospho-Akt and Sirtuin1 proteins, both of which have been reported to maintain tumour progression. 5MQ can further be investigated and modified for anti-cancer therapy.

The role of lymphadenectomy in patients with stage III&IV uterine serous carcinoma: Results of multicentric Turkish study.

OBJECTIVE: The aim of this study was to evaluate clinicopathological features, oncological outcome and prognostic factors for recurrence in advanced stage uterine serous carcinoma (USC) patients. METHODS: Patients with 2009 International Federation of Gynecology and Obstetrics stage III&IV uterine serous carcinoma were enrolled from 4 gynecologic oncology centers and a study group was created. Response to therapy was evaluated according to the WHO criteria. Progression-free survival (PFS) and overall survival (OS) estimates were determinated by using the Kaplan-Meier method. Survival curves were compared with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Entire cohort included 63 patients. Median age of cohort was 64 years. Thirty-five (55.6 %) patients were stage IV. Lymphadenectomy was performed in 57 (90.5 %) patients and lymph node metastasis was positive in 45 (71.4 %) patients. Maximal cytoreduction (no residue tumor) was achieved in 53 (84.1 %) patients. However, optimal cytoreduction (residue tumor ≤1 cm) was achieved in 6 (9.5 %) patients and suboptimal cytoreduction (residue tumor >1 cm) was achieved in 3 (4.8 %) patients. Median follow-up time was 19 (range;1-152) months. Complete clinical response was obtained in 58 (92.1 %) patients after standard adjuvant therapy. Disease failure was detected in 25 patients. Study group had a 2-year PFS of 51 % and 2-year OS of 80 %. On multivariate analysis, performing lymphadenectomy was an independent prognostic factor for PFS (Odds ratio: 24.794, 95 % Confidence Interval: 4.214-145.869; p < 0.001). CONCLUSION: Lymphadenectomy should be a part of the standard surgical therapy in advanced stage USC.

Nicotinamide N-methyltransferase overexpression may be associated with poor prognosis in ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer-related mortality in women. Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme and there is growing evidence to suggest that it plays an important role in cancer progression. This is the first study to examine the expression of NNMT in serous ovarian cystadenomas, serous borderline tumours, low grade serous carcinomas (LGSC) and high grade serous carcinomas (HGSC) and investigate the potential independent association of NNMT expression with survival. Tissue samples were analysed immunohistochemically for NNMT expression. The stromal NNMT score was significantly higher in HGSC compared to serous cystadenomas and serous borderline tumours (p < .001, p < .043, respectively). The mean stromal NNMT score of patients with HGSC was significantly higher than patients with LGSC (p = .043). Patients with low expression of NNMT had a significantly higher mean recurrence-free survival than patients with high expression (p = .036). NNMT may support tumour progression in ovarian cancer by promoting desmoplastic stromal tumour reaction. NNMT overexpression may be associated with poor prognosis and can be a therapeutic target in ovarian cancer.IMPACT STATEMENTWhat is already known on this subject? Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that is overexpressed in many malignancies. Its overexpression was shown to lead to histone hypomethylation, which in turn can decrease and increase the expression of tumour suppressor proteins and onco-proteins, respectively. NNMT was also shown to play a role in epithelial-to-mesenchymal transition, which is critical in tumour progression and the stromal tumour reaction. The stromal tumour reaction was recently targeted with promising therapeutic results in ovarian cancer.What do the results of this study add? The expression of NNMT in various ovarian neoplasms including serous cystadenomas, borderline tumours and serous carcinomas has not been studied and independently associated with poor survival, previously. This study suggests that NNMT is progressively overexpressed in the stroma of ovarian neoplasms from benign cysts to HGSCs. NNMT overexpression appears to be independently associated with poor survival in ovarian cancer.What are the implications of these findings for clinical practice and/or further research? The implications of these findings are that NNMT may play an important role in the stromal tumour reaction, and therefore its overexpression may contribute to poor survival. NNMT overexpression may be an important target of ovarian cancer therapy.

Prognostic significance of solid growth in endometrioid endometrial adenocarcinoma.

BACKGROUND: Endometrioid endometrial cancer is the most common histological subtype of endometrial adenocarcinoma. In the FIGO grading scheme, both architectural and nuclear grade are taken into consideration. However, the specific impact of solid growth alone on endometrioid endometrial adenocarcinoma outcome is not well documented. We sought to assess the degree of impact of solid growth on lymphovascular space invasion (LVSI), myometrial invasion, tumor size, FIGO stage, lymph node metastasis (LNM), relapse-free survival (RFS) and disease-specific survival (DSS). METHODS: Paraffin blocks of 269 patients treated for endometrioid endometrial cancer were retrospectively analyzed with morphometry for solid growth percentages. RESULTS: A statistically significant cut-off value of 1% solid growth was found for predicting LNM and advanced stage (III or IV), myometrial invasion and LVSI (p < 0.001) and a cut-off value of 8% was found for predicting adverse survival outcome (p < 0.001). The mean DSS was significantly higher in patients with < 6% solid growth compared to patients with 6-50%, 51-75% and > 75% solid growth (p < 0.001). Although, the mean RFS and DSS were lowest in patients with 51-75% solid growth, this did not reach statistical significance in comparison to 6-50% and > 75% (p > 0.05). CONCLUSION: Although > 75% solid growth was most significantly associated with many of the adverse prognostic factors, this subset did not provide prognostic superiority in predicting adverse survival when compared to subsets within 6-75% solid growth. In conclusion, although no statistically significant difference in survival was found among subdivisions of architectural grades 2 and 3, solid growth, especially ≥ 8%, appeared to be an independent prognostic factor for survival in patients with early-stage endometrioid endometrial cancer.

Expression and Clinical Significance of Nicotinamide N-Methyltransferase in Cervical Squamous Cell Carcinoma.

Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme, overexpressed in various human malignancies. It is associated with cancer progression and resistance to treatment. The role of NNMT in cervical cancer has not been studied thus far. We aimed to evaluate expression of NNMT in cervical squamous cell carcinoma (SCC) and investigate its clinical significance. NNMT expression was assayed by use of immunohistochemistry in 61 cases of SCC, 11 cases of high-grade squamous intraepithelial lesion, 17 cases of low-grade squamous intraepithelial lesion, and 51 benign cervical tissues. NNMT immunoreactivity was scored based on staining intensity and percentage of positively stained cells. The expression of NNMT was significantly higher in SCC than in benign tissue, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion (P<0.001). NNMT expression in benign tissue was significantly lower than in low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. When stratified according to stage, NNMT expression was significantly higher in patients with stage III and IV than those in stage I and II disease (P=0.009). For all stages, patients with metastatic pelvic or para-aortic lymph nodes had significantly higher NNMT expression than patients without nodal involvement (P=0.001). Although preliminary, this is the first study to detect overexpression of NNMT in SCC and increased expression associated with advanced stage and metastatic lymph nodes. NNMT should be investigated further in cervical cancer as a potential therapeutic target and a prognostic indicator.

Nicotinamide N-methyltransferase expression and its association with phospho-Akt, p53 expression, and survival in high-grade endometrial cancer

Background/aim: Nicotinamide N-methyltransferase (NNMT) is an enzyme that is overexpressed in malignancies. NNMT expression has not been previously studied in endometrial cancer (EC). Increased phospho-Akt (pAkt) levels in response to NNMT overexpression have been reported in in vitro studies of different cancer types. We assayed NNMT expression in primary and metastatic high-grade EC and investigated the relationship of NNMT with p53, pAkt, and survival. Materials and methods: NNMT, pAkt, and p53 expressions were assayed in 100 tissue samples of benign endometria, primary EC, and metastatic EC by immunohistochemistry. Results: The NNMT immunoreactivity score was significantly higher in primary high-grade EC than benign endometrial tissue (P = 0.001). NNMT expression in metastatic tissue was significantly higher than in primary cancer (P < 0.001). Metastatic stromal NNMT expression was significantly higher than that of the adjacent tumor and stroma adjacent to the primary tumor. p53 expression in the primary tumor showed a significant positive correlation with omental NNMT and pAkt expression. NNMT expression was also correlated with pAkt expression in metastatic tissue. NNMT overexpression in metastatic tissue was associated with decreased survival (P = 0.039). Conclusion: This study suggests that NNMT may promote cancer progression and that NNMT overexpression is associated with aberrant p53 expression, pAkt, and poor survival. NNMT's role in cancer progression could make it a target of EC therapy.

Subclinical inflammation markers in hyperemesis gravidarum and ketonuria: A case-control study.

INTRODUCTION: Subclinical inflammation markers play a significant role in hyperemesis gravidarum (HEG). Simple hematological markers such as mean platelet volume (MPV), platelet distribution width (PDW), neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), plateletcrit (PCT), and platelet-to-lymphocyte ratio (PLR) have been shown to reflect inflammatory burden and disease activity in several disorders. Ketonuria is a parameter used in the diagnosis of severe HEG, but its correlation with disease severity remains controversial. The relationship of subclinical inflammation markers with degree of ketonuria has not been examined previously. In this study, we aimed to determine the diagnostic value of these subclinical inflammation markers and the relationship between these markers and grade of ketonuria in patients with HEG. MATERIALS AND METHODS: A total of 94 pregnant women with a diagnosis of HEG and 100 gestational age-matched healthy pregnant women were enrolled in this retrospective study. MPV, PDW, NLR, PLR, PCT, and ketonuria were calculated and analyzed from complete blood cell counts and total urine analyses. RESULTS: Lymphocyte count was significantly higher in the control group (P < 0,001); NLR and PLR values were significantly higher in the HEG group (P < 0,001). Among inflammation markers, RDW increased significantly (P = 0,008) with an increase in ketonuria in patients with HEG. A statistically significant correlation was found between white blood cell (WBC) and NLR, PLR, PCT. A moderate uphill relationship was observed between NLR and WBC and a weak uphill linear relationship was observed between WBC and PLR and between WBC and PCT. CONCLUSIONS: PLR and NLR can be considered effective markers to aid in the diagnosis of HEG. No marker was found to correlate with ketonuria grade except RDW, although the relationship of the severity of ketonuria with severity of disease is controversial. RDW increases as the degree of ketonuria increases.