Endometriosis is a very common disease that is characterized by increased formation of estradiol and disturbed progesterone action. This latter is usually explained by a lack of progesterone receptor ...B (PR-B) expression, while the role of pre-receptor metabolism of progesterone is not yet fully understood. In normal endometrium, progesterone is metabolized by reductive 20α-hydroxysteroid dehydrogenases (20α-HSDs), 3α/β-HSDs and 5α/β-reductases. The aldo-keto reductases 1C1 and 1C3 (AKR1C1 and AKR1C3) are the major reductive 20α-HSDs, while the oxidative reaction is catalyzed by 17β-HSD type 2 (HSD17B2). Also, 3α-HSD and 3β-HSD activities have been associated with the AKR1C isozymes. Additionally, 5α-reductase types 1 and 2 (SRD5A1, SRD5A2) and 5β-reductase (AKR1D1) are responsible for the formation of 5α- and 5β-reduced pregnanes. In this study, we examined the expression of PR-AB and the progesterone metabolizing enzymes in 31 specimens of ovarian endometriosis and 28 specimens of normal endometrium. Real-time PCR analysis revealed significantly decreased mRNA levels of
PR-AB,
HSD17B2 and
SRD5A2, significantly increased mRNA levels of
AKR1C1,
AKR1C2,
AKR1C3 and
SRD5A1, and negligible mRNA levels of
AKR1D1. Immunohistochemistry staining of endometriotic tissue compared to control endometrium showed significantly lower PR-B levels in epithelial cells and no significant differences in stromal cells, there were no significant differences in the expression of AKR1C3 and significantly higher AKR1C2 levels were seen only in stromal cells. Our expression analysis data at the mRNA level and partially at the cellular level thus suggest enhanced metabolism of progesterone by SRD5A1 and the 20α-HSD and 3α/β-HSD activities of AKR1C1, AKR1C2 and AKR1C3.
BACKGROUND: The objective of this study was to estimate the frequency of Y chromosome microdeletions in the Slovenian population of infertile men and to analyse the consequences of mutation in ...respect to clinical severity and prognosis. METHODS: In a controlled clinical study at the university-based medical genetics service and infertility clinic, 226 infertile men undergoing ICSI were tested. The main outcome measures included polymerase chain reaction amplification of 16 genes and gene families and 42 sequence-tagged sites in the non-recombining region of the Y chromosome, semen, testicular volume and testicular histological analysis, serum FSH concentrations, fertilization and respective pregnancy rates. RESULTS: The incidence of deletions was 4.4%: 8.6% in men with azoospermia and 1.5% in men with oligoasthenoteratozoospermia. Isolated gene deletions were not identified. No statistically significant differences in clinical outcome measures were found in patients with mutations versus patients without mutations. High fertilization (49%) and pregnancy (43%) rates with sperm of patients with Y chromosome deletions were obtained. CONCLUSIONS: Testing for gene-specific microdeletions does not contribute significantly to the sensitivity of microdeletion test. Fertilization and pregnancy rates obtained using sperm of patients with Y chromosome deletions were comparable with those achieved in conventional IVF.
Müllerian papilloma is a rare benign tumor of the female genital tract. It mostly affects girls less than five years old. After the treatment long-term follow-up is needed as there is a chance of ...recurrence, but even then the prognosis is excellent.
A 19-year-old girl with Proteus syndrome presented with vaginal bleeding. The histological examination revealed Müllerian papilloma of the uterine cervix and large bilateral ovarian cystadenomas. The patient was treated with a radical operation, because there were signs of more aggressive behavior in the tumor. The patient is alive and free of disease five years after the operation.
The medical care of patients affected by rare disorders depends heavily on experiences gained from cases published in the medical literature. Since there is not much experience with tumors in Proteus syndrome we believe that this case can aid in shedding light on this subject.
Primary embryonal rhabdomyosarcoma (RMS) arising from the uterine cervix is a rare and extremely malignant entity. Young women aged 12-26 years are mostly affected. Before the introduction of ...effective adjuvant chemotherapy, the prognosis of these lesions was poor.
A 16-year-old girl presented with vaginal bleeding. The histological examination revealed embryonal RMS of the uterine cervix. The patient was treated with a combination of surgery, chemotherapy and radiotherapy. The patient was alive and free of disease five years after the operation.
A combined modality approach to treating RMS using surgery, multidrug chemotherapy, and radiotherapy has significantly improved survival. The medical community should keep in mind that embryonal RMS of the uterine cervix, despite its malignancy and rarity, can be cured if timely and adequate treatment is given.
Malignant melanoma metastases to the female genital tract in only 2.5% of cases. Melanoma is characterized by clinical variability and unpredictable biological behavior with long remissions and ...relapses that develop rapidly.
A 57-year-old woman was admitted for hypogastric pain and weight loss. She had presented enucleation of the right eye six years before for malignant choroid melanoma. Gynaecological examination revealed enlarged ovaries. Bilateral salpingo-oophorectomy, hysterectomy, and omentectomy were performed. Final pathology diagnosed a choroidal metastatic melanoma (CMM). The patient died seven months later. Only seven cases of CMM have been reported in the literature. Patients affected by CMM ranged in age from 38 to 83 years (median 51.2 years), the time to relapse ranged from 3-25 years (median 51.2 years), the size of the cysts ranged from 4-17 cm (median 9.7 cm) and the survival period ranged from 2-14 months (median 8.1 months).
Malignant melanoma is misdiagnosed because of lack of discriminatory symptoms, increased tumor markers, characteristic imaging findings and the capacity to mimic other tumors. Today CMM still represents a challenge for gynecologic oncologists.
Endometrial cancer is the most common malignancy of the female genital tract. Its incidence correlates with prolonged estrogen stimulation unopposed by progesterone or synthetic progestins. Estrogen ...and progestin action is regulated at the pre-receptor level, by interconversion of active hormones (estradiol (E2), progesterone (P)) with their inactive counterparts (estrone (E1), 20α-hydroxyprogesterone (20α-OHP)) in target tissues. Expression of enzymes that control the ratio of E2 and P may thus play role in the disease process. We first confirmed that AKR1C1 (human 20α-hydroxysteroid dehydrogenase) in a cellular context inactivates P by forming 20α-OHP but does not catalyze the reverse reaction. We next examined the expression of AKR1C1 and AKR1C3 (type 5 17β-hydroxysteroid dehdyrogenase) in 16 paired specimens of endometrial cancer and adjacent normal endometrium. Quantification by isoform specific real-time PCR revealed higher expression of AKR1C1 in nine specimens and higher expression of AKR1C3 in four specimens of endometrial cancer. Importantly, upregulation of both enzymes in the same specimen was observed. Since AKR1C1 inactivates P its elevated expression in diseased endometrium may contribute to diminished protection by P, while eleveated expression of AKR1C3 which forms E2 in vivo, may contribute to the enhanced estrogen action. It is suggested that the expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2
Malignant melanoma (MM) accounts for 3% of cancers that affect women and results in less than 1% of cancer deaths. It is characterized by clinical variability and unpredictable biological behavior. ...Fewer than ten cases of amelanotic MM (AMM) have been reported in literature.
A 61-year-old woman was admitted for vaginal spotting. A huge, soft cervix with an exophytic lesion was biopsied. A clear cell carcinoma, FIGO Stage IB1, was diagnosed and radically treated. The final pathology showed an AMM of the cervix positive for PAS and HMB 45. The patient is clinically free of disease ten years postoperatively.
Malignant melanoma of the cervix is often misdiagnosed because of non discriminatory features and the capacity to mimic other tumors. Malignant melanoma of the cervix needs to be diagnosed as quickly as possible because a timely therapy and a long and careful follow-up might result in better survival.
Estrogen-dependent endometrial cancer is related to unopposed and prolonged estrogen stimulation. We examined the expression of estrogen-metabolizing enzymes in correlation with the ERα and ERβ ...estrogen receptors in human endometrial Ishikawa adenocarcinoma cells and in endometrial cancer specimens and adjacent normal endometrium from the same patients. Real-time PCR analysis revealed that both estrogen receptors and selected estrogen-metabolizing enzymes were expressed in the Ishikawa cells and in endometrial tissue. We detected higher expression of ERα than ERβ, higher expression of sulfatase than sulfotransferase and low expression of aromatase in the Ishikawa cells and the tissue, as well as higher levels of type 2 17β-hydroxysteroid dehydrogenase (17β-HSD) in normal and diseased tissue than in the Ishikawa cells. When we compared the expression in endometrial cancer samples and in the adjacent normal endometrium, ERα and ERβ, sulfatase and sulfotransferase were seen to be downregulated in the majority of the cancerous tissue specimens.
BACKGROUND: The objective of this study was to estimate the frequency of Y chromosome microdeletions in the Slovenian population of infertile men and to analyse the consequences of mutation in ...respect to clinical severity and prognosis. METHODS: In a controlled clinical study at the university-based medical genetics service and infertility clinic, 226 infertile men undergoing ICSI were tested. The main outcome measures included polymerase chain reaction amplification of 16 genes and gene families and 42 sequence-tagged sites in the non-recombining region of the Y chromosome, semen, testicular volume and testicular histological analysis, serum FSH concentrations, fertilization and respective pregnancy rates. RESULTS: The incidence of deletions was 4.4%: 8.6% in men with azoospermia and 1.5% in men with oligoasthenoteratozoospermia. Isolated gene deletions were not identified. No statistically significant differences in clinical outcome measures were found in patients with mutations versus patients without mutations. High fertilization (49%) and pregnancy (43%) rates with sperm of patients with Y chromosome deletions were obtained. CONCLUSIONS: Testing for gene-specific microdeletions does not contribute significantly to the sensitivity of microdeletion test. Fertilization and pregnancy rates obtained using sperm of patients with Y chromosome deletions were comparable with those achieved in conventional IVF.
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