Methylation of the Selected TP53 Introns in Advanced-Stage Ovarian Carcinomas.

Objective: Advanced-stage ovarian cancer (OC) is among the most fatal female genital tract neoplasms worldwide. Although different genetic mechanisms have been shown to be involved in ovarian carcinogenesis, the role of TP53 introns methylation is still unresolved. We performed methylation analysis of introns 1, 3, and 4 of the TP53 to identify patterns in primary stage III OCs, corresponding metastases, and healthy tissues. Methods: The study involved samples of paraffin-embedded tissues obtained from 80 patients with stage III OCs, who underwent surgery at the Department of Gynecology and Gynecologic Oncology of the Military Institute of Medicine in Warsaw, Poland. Altogether, 40 serous-type G2/3 OCs and 40 endometrioid-type G2/3 OCs were included. From the same patient, metastatic and normal tissues were simultaneously analyzed. As a control group, 80 tissue samples were collected from patients after bariatric operations. Human ovarian cancer A2780 cell line was also investigated. Total genomic DNA was isolated from paraffin-embedded tissue blocks and the methylation analysis was performed by bisulfite DNA conversion, DNA amplification with specific primers, cloning, and DNA sequencing. Results: All of the samples of intron 1 of TP53 were un-methylated in OCs, metastatic tissues, and in healthy tissues from the same patient. Also, no methylation of TP53 intron 1 was detected in cells from the human A2780 ovarian cancer cell line and in all samples from control group. In all samples, introns 3 and 4 of the TP53 were methylated in primary tumors, metastatic tissue, and in healthy tissue from the same patient, in human A2780 ovarian cell line, and in DNA samples from healthy patients. None of the clinicopatholocal features was related to the TP53 introns methylation status. Conclusions: Our data on TP53 introns methylation sheds new light on the mechanism of p53 activity for a better understanding of cancer biology. The study suggests the existence of an additional regulation rule of TP53 activity that involves demethylation-methylation mechanisms. Methylation at introns 3 and 4 may also overall help in protecting TP53 against damage by viral restrictases or viral DNA integration.

Spontaneous regression of fetal pleural effusion in pregnancy complicated with Herpes simplex infection: Clinical presentation and literature review.

Fetal primary hydrothorax is a rare congenital anomaly with an estimated incidence of 1:10,000-15,000 pregnancies, with an unpredictable clinical course, ranging from spontaneous resolution to fetal death. A case of unilateral fetal pleural effusion was diagnosed at 35th week of gestation during a routine ultrasonographic fetal assessment in an uncomplicated pregnancy. A large echogenic collection of fluid was revealed in the right pleural cavity, together with atelectasis of the right lung, as well as displacement of heart and mediastinal structures to the left side of thorax. The patient was also diagnosed with polyhydramnios and there was a disproportion of heart ventricles volume. No other fetal structural abnormalities were detected and there were no symptoms of edema. Fetal biometrics was consistent with the gestational age. In echocardiography, fetal heart was structurally and functionally normal. Screening tests for congenital infections of the fetus were negative. Autoimmune fetal hydrops was excluded after laboratory tests. There was no parents' consent for the analysis of the karyotype. The patient presented clinical symptoms and was diagnosed with Herpes simplex virus infection and was treated with oral acyclovir. Serial fetal ultrasound exams showed gradual decrease in pleural fluid volume up to complete resolution in 38th week of pregnancy. Pregnancy was ended in the 38th week of gestation with a cesarean delivery of a healthy neonate. It is yet to be determined if there is a direct association between Herpes simplex virus infection in pregnancy and the risk of fetal pleural effusion. The incidence of fetal pleural effusion is low and the neonatal outcome difficult to be predicted. The optimum management of fetal pleural effusion should be subject to further studies to determine the best clinical practice.

HPV16 E6 Gene Transcripts in Primary Type II Endometrial Carcinomas.

BACKGROUND/AIM: Data on the prevalence of human papilloma virus (HPV) DNA in different subtypes of endometrial carcinomas (EC) are limited. PATIENTS AND METHODS: We investigated the incidence of HPV16 DNA E6/E7 transcripts in 47 type I (endometrioid-type) tumors and eight type II (non-endometrioid-type) uterine neoplasms applying PCR-based technology. Immunohistochemical staining in HPV16 positive cases was also performed, and seven lymph node metastases were examined for the presence of HPV16 DNA E6/E7. RESULTS: None of the type I ECs was positive for HPV16 E6 gene transcripts; however, four out of 8 (50%) type II ECs (two out of four papillary-serous and two out of four clear-cell carcinomas) were positive for HPV16 E6 transcripts. The difference in HPV16 E6 transcripts between endometrioid and non-endometrioid neoplasms was statistically significant (p=0.0011). Apart from the cancer subtype, none of the EC clinicopathological features were related to HPV16 E6 positivity. None of 55 ECs contained an HPV16 E7 gene transcripts. All slides from gene-positive samples revealed intense immunostaining reactions. Interestingly, the virus was not detected in any of seven lymph node metastases, including four from HPV16-positive primary tumors. CONCLUSION: HPV16 E6 gene transcripts may be present in ECs, primarily in the non-endometrioid (type II) uterine cancer subtypes. HPV E6/E7 DNA transcripts were not found in lymph node metastases, even when the primary tumors harboured HPV DNA.

Spontaneous unilateral exophthalmos after a vaginal delivery.

INTRODUCTION: Spontaneous orbital exophthalmos is an extremely rare incident during a vaginal delivery. In most cases, it is associated with venous malformations and presents spontaneous resolution. CASE DESCRIPTION: We report a case of orbital hematoma after vaginal delivery due to a superior ophthalmic vein rupture. The patient presented proptosis of the right eye and diplopia immediately after the delivery and was diagnosed with unilateral orbital hematoma. The patient was given conservative treatment with complete resolution of clinical symptoms 4 weeks after the delivery. CONCLUSION: Increased abdominal pressure during a vaginal delivery may lead to a spontaneous orbital hemorrhage.

Immunohistochemical results and case report of an incidental finding of uterine polypoid adenomyoma after long-time therapy for metrorrhagia.

We present a 25-year-old female woman with a 9-year history of metrorrhagia, in whom a uterine polypoid adenomyoma (UPA) was incidentally detected. Intense nuclear staining in the uterine adenomyoma tissue showed an immunoreaction with BAF250a/ARID1A, Arginase-2 as well as 1LRH-2E1/NR5A2, suggesting a role of these proteins and transcriptional activity of their genes in uterine polypoid adenomyoma development. Neither Nidogen-2 nor SF-1/NR5A1 were expressed in UPA.

Ovarian adult-type granulosa cell tumor concomitant with simple endometrial hyperplasia: a case study with selected immunohistochemistry.

Ovarian adult-type granulosa cell tumors are often associated with endometrial hyperplasia or even uterine cancer. Herein, we present a case report of a 65-year-old female patient who had undergone curettage of the uterine cavity several times due to abnormal and irregular uterine bleeding. Owing to recurrent episodes of vaginal bleeding as well as ineffective pharmacological treatment of simple endometrial hyperplasia without atypia, the patient underwent a laparoscopically-assisted vaginal hysterectomy. Owing to an enlarged right ovary with bluish color, intra-operative pathological examination was immediately performed. Surprisingly, an ovarian adult-type granulosa cell tumor was diagnosed, and the surgery was extended to pelvic lymphadenectomy and omentectomy. Immunohistochemical staining with selected antibodies (Arginase 2, Nidogen 2, BAF250a/ARID1A, GPR30, SF-1/NR5A, and 1LRH-2E1/NR5A2) was also performed. In conclusion, in cases of recurrent vaginal bleeding concomitant with endometrial hyperplasia, the existence of rare ovarian tumors connected with extensive estrogenic stimulation must be taken into account. Immunostaining with selected antibodies (Arginase 2, Nidogen 2, ARID1A, or GPR30) may help elucidate the possible molecular mechanisms associated with the BAF250a/development of various ovarian/endometrial abnormalities.