KLK10 exon 3 unmethylated PCR product concentration: a new potential early diagnostic marker in ovarian cancer? - A pilot study.

BACKGROUND: KLK10 exon 3 hypermethylation correlated to tumor-specific lack of KLK10 expression in cancer cell lines and primary tumors. In the present study we investigate the possible role of KLK10 exon 3 methylation in ovarian tumor diagnosis and prognosis. RESULTS: Qualitative methylation-specific PCR (MSP) results did not show statistically significant differences in patient group samples (normal and tumor) where all samples were positive only for the unmethylated-specific PCR except for two malignant samples that were either doubly positive (serous carcinoma) or doubly negative (Sertoli-Leydig cell tumor) for the two MSP tests. However, KLK10 exon 3 unmethylated PCR product concentration (ng/µl) showed statistically significant differences in benign and malignant patient group samples; mean ± SD (n): tumor: 0.077 ± 0.035 (14) and 0.047 ± 0.021 (15), respectively, p-value = 0.011; and normal: 0.094 ± 0.039 (7) and 0.046 ± 0.027 (6), respectively, p-value = 0.031. Moreover, ROC curve analysis of KLK10 exon 3 unmethylated PCR product concentration in overall patient group samples showed good diagnostic ability (AUC = 0.778; p-value = 0.002). Patient survival (living and died) showed statistically significant difference according to preoperative serum CA125 concentration (U/ml); median (n): 101.25 (10) and 1252 (5), respectively, p-value = 0.037, but not KLK10 exon 3 unmethylated PCR product concentration (ng/µl) in overall malignant patient samples; mean ± SD (n): 0.042 ± 0.015 (14) and 0.055 ± 0.032 (7), p-value = 0.228. CONCLUSION: To the best of our knowledge, this is the first report on KLK10 exon 3 unmethylated PCR product concentration as potential early epigenetic diagnostic marker in primary ovarian tumors. Taken into account the limitations in our study (small sample size and semi-quantitative PCR product analysis) further studies are strongly recommended.

Ovarian function in female survivors of childhood malignancies.

BACKGROUND: Chemotherapy-induced infertility is a common side effect observed in women of fertile age after treatment for malignant disease. OBJECTIVES: to study gonadal function and fertility in female survivors of childhood malignancies. PATIENTS AND METHODS: Study included 30 female cancer survivors and 30 age-matched healthy females as a control group. Data collected regarding; type of malignancy, age at diagnosis, duration on and off treatment, treatment received (radiation or chemotherapeutic regimens), sexual, menstrual, pregnancy, and fertility histories were also recorded. Laboratory investigations included; T4, thyroid stimulating hormone (TSH), leutinizing hormone (LH), follicular stimulating hormone (FSH), and anti-Mullerian hormone (AMH). Pelviabdominal ultrasound was done to estimate the mean ovarian volume. RESULTS: Among patients; 80% had normal menarche and 6 (20%) had delayed menarche (P > .05). There was higher LH and FSH levels and lower AMH levels in patients (P < .05) with no significant difference in thyroid function tests (P > .05). Lower mean ovarian volume was observed among female survivors (6.32 ± 2.31 cm(3)) (P = .041). There was a higher FSH and LH levels among female survivors of solid tumors compared to those with hematological tumors (P = .05 and .04 respectively). There was a significant positive correlation between FSH level and patients' age at start of malignancy (r = 0.65, P = .014), age of menarche (r = 0.74, P = .036), and duration of treatment (r = 0.54, P = .025).There was a significant negative correlation between age of menarche and AMH level (r = -0.61, P = .03). CONCLUSION: Female survivors of childhood malignancies had reduced ovarian reserve and reduced mean ovarian volume, especially those with older age, older age of menarche, and longer treatment duration.

Direct visual inspection of the cervix with Lugol iodine for the detection of premalignant lesions.

OBJECTIVE: To evaluate the feasibility and efficiency of direct visual inspection after Lugol iodine painting in detecting cervical premalignant and malignant lesions. MATERIALS AND METHODS: This study included 1,012 women recruited from gynecology outpatient clinic screened for premalignant or malignant lesions of the cervix. All women underwent cervical smear test, direct visual inspection of the cervix after painting with acetic acid (DVI-A) and after painting with Lugol iodine (DVI-LI). Abnormal test results were referred for colposcopy and biopsy. RESULTS: Cervical smears were abnormal in 24 women (2.4%). Direct visual inspection of the cervix after painting with acetic acid test was abnormal in 92 women (9.1%). Direct visual inspection after Lugol iodine painting test was abnormal in 93 women (9.2%). There were 106 women (10.5%) referred for colposcopy, with 88 women (8.8%) having biopsies taken. Biopsies showed premalignant and malignant lesions in 44 cases only. There were 35 low-grade squamous intraepithelial lesion, 5 high-grade squamous intraepithelial lesion, and 4 cervical cancers. Test efficiency parameters particularly sensitivity, specificity, and positive and negative predictive values of DVI-LI were 97.7%, 94.8%, 46.2%, and 99.9%, respectively; those of cytology were 22.7%, 97.6%, 41.7%, and 96.6%, respectively, and those of DVI-A were 90.9%, 94.6%, 43.5%, and 99.6%, respectively. CONCLUSIONS: Direct visual inspection after Lugol iodine painting is feasible and easy to perform with superior sensitivity to cervical cytology and DVI-A in detecting cervical premalignant and malignant lesions. Direct visual inspection after Lugol iodine painting can be used as an efficient primary screening tool with a satisfactory low biopsy rate in low resources settings.