Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions.

OBJECTIVES: The ovarian tumor microenvironment, ie, the peritoneal fluid, is an intriguing research subject. The goal of this study was to assess the behavior of selected cytokines and growth factors within the peritoneal fluid in pathologies associated with ascites and to assess the relationship between the levels of these substances and select prognostic factors of ovarian cancer. METHODS: A total of 74 patients were enrolled in the study, including 36 patients with ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal fluid collected during surgical procedures was used to assess the levels of interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and human epididymis protein 4. The median levels of these factors were compared between the two groups, and the levels of selected factors were assessed in the ovarian cancer group with regard to the clinical stage of cancer, tumor differentiation, presence of peritoneal spread and positive peritoneal fluid cytology results. The diagnostic value of the analyzed proteins within the peritoneal fluid was also assessed. RESULTS: Differences were observed between the patients with ovarian cancer and the patients with benign gynecological conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF-15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf-1, TRAIL, and human epididymis protein 4 levels between the two study groups. Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and higher OPG values in advanced cancers compared to less-advanced cancers. Tumor differentiation was associated with significantly lower SCF values in the group of poorly differentiated tumors. A significant reduction in SCF values and a significant increase in OPG and IL-6 values were also observed within cancer cell-positive peritoneal fluid. Peritoneal spread was associated with higher levels of TRAIL, osteonectin, and IL-6 in ovarian cancer patients. CONCLUSION: On the basis of the conducted studies, it appears that of the studied factors, GDF-15, SCF, and OPG deserve special attention in the context of future research on the tumor microenvironment. With regard to diagnostics, attention should be given primarily to GDF-15, IL-6, and osteonectin.

Serum HE4, CA125, YKL-40, bcl-2, cathepsin-L and prediction optimal debulking surgery, response to chemotherapy in ovarian cancer.

BACKGROUND: The most important prognostic factor in the ovarian cancer is optimal cytoreduction. The neoadjuvant chemotherapy, an only optional method of treatment in this case and is still the subject of debate. The object of this study was to evaluate the usefulness of markers: CA 125, HE4, YKL-40 and bcl-2 as well as cathepsin L in predicting optimal cytoreduction and response to chemotherapy. METHODS: Sera were secured preoperatively. The division into groups was performed retrospectively depending on the method of treatment (surgery vs neoadjuvant chemotherapy) as well as on response to chemotherapy (sensitive vs resistant vs refractory). Comparisons were made between groups, and the diagnostic usefulness of tested proteins was examined. RESULTS: We found that statistically significant differences between primary operated patients and patients undergoing neoadjuvant chemotherapy were applicable only to the tumour markers (CA125 1206.79 vs 2432.38, p=0.000191; HE4 78.87 vs 602.45, p=0.000004; YKL-40 108.13 vs 203.96, p=0.003991). Cathepsin-L and Bcl-2 were statistically insignificant. The cut-off point values were determined for the CA 125 (345 mIU/ml), HE4 (218.43 pmol/L) and YKL-40 (140.9 ng/ml). The sensitivity, specificity, PPV and NPV were as follows: CA125 (83.3%; 75%; 80.6%; 78.3%), HE4 (86.6%; 91.3%; 92.9%; 84%) and YKL-40 (75%; 83.3%; 84%; 74.1%). CONCLUSION: Among the tested proteins the HE4 marker appears to be helpful in forecasting of optimal cytoreduction and possibly also of the prediction of response to platinum analogues used in first-line treatment of ovarian cancer.

HE4 tumor marker concentration in neoplastic peritoneal effusion and in peritoneal fluid associated with benign gynecological diseases.

BACKGROUND: The aim of our study was to evaluate the behaviour of the human epididymis protein 4 (HE4) in the peritoneal fluid encountered in various female genital diseases. METHODS: We enrolled 139 patients, 40 with ovarian cancer (group I), 82 with benign diseases (group II), and 17 with other malignant neoplasms (group III). The HE4 tumor marker concentrations were determined in serum, in the peritoneal effusion and ovarian cyst/ tumor fluids, CA125 in the serum only. We compared the groups, examined correlations and determined corresponding ROC curves. We evaluated the relationship between the HE4 marker concentration in the peritoneal effusion in the group I, depending on the selected prognostic parameters. RESULTS: The HE4 median value between the study groups did not differ statistically significantly and were as follows: in group I 3322 pmol/L, in the group II 2150 pmol/L and in the group III 627 pmol/L (p = 0.206376 for the groups I and II, p = 0.05929 for the groups I and III and p = 0.0797 for the groups II and III. In group I there were no differences found in the HE4 concentrations in the peritoneal fluid, depending on the stage, grade, the presence of neoplastic cells and the peritoneal dissemination. CONCLUSIONS: The HE4 marker concentrations in the peritoneal fluid are highly irrespective of the pathology observed in the female sexual organ. Therefore, it seems that its determinations in the peritoneal fluid are completely useless in terms of diagnostics. More research is needed on the role of the HE4 marker, especially the place of its formation and possible use in the targeted therapy.

[Characteristics of selected clinical features in BRCA1 mutation carriers affected with breast cancer undergoing preventive female genital tract surgeries]. / Charakterystyka wybranych aspektów klinicznych u kobiet, nosicielek mutacji genu BRCA1 poddanych operacjom profilaktycznym narzadu plciowego leczonych uprzednio z powodu raka piersi.

AIM: Evaluation of patient age and time of the prophylactic surgery as well as incidence of genital cancers and precancerous states observed in histopathology of the postoperative material from BRCA1 gene mutation carriers previously treated for breast cancer. MATERIAL AND METHODS: 206 carriers of one of the three most common BRCA1 gene mutations (5382insC, C61G and 4153delA) in the Polish population, who were offered the option of prophylactic salpingo-oophorectomy The study group comprised 85 patients with the diagnosis of breast cancer before gynecological preventive surgery The study group was further divided into two subgroups for more detailed assessment of the tested variables. The first subgroup included 67 patients with breast cancer (unilateral or bilateral synchronous). The second subgroup included 18 patients with bilateral metachronous (the second diagnosis of breast cancer was at least 12 months after the first breast cancer diagnosis). The control group consisted of 121 patients with no cancerous lesions before preventive gynecologic surgery The patients undergoing prophylactic treatment had no prior symptoms in female sexual organ and no changes in the diagnostic tests. RESULTS: The patients with a history of breast cancer underwent genetic testing and preventive surgery of the genital tract at a significantly later age than controls (respectively p = 0.0003, p = 0.0006). The patients with bilateral metachronous breast cancer underwent preventive surgery significantly earlier (p = 0.03). There was a trend indicating a 2.5 times higher risk of developing ovarian cancer among BRCA1 mutation carriers who had already been diagnosed and treated for breast cancer when compared to women without breast cancer diagnosis. The incidence of other genital cancers and precancerous states in BRCA1 gene mutation carriers with history of breast cancer was not statistically significant as compared to controls. Data on the clinical stage, morphological grade, histological type, age and type of pathology and the type of BRCA1 gene mutation did not show a statistically significant difference between the groups. CONCLUSIONS: Each patient diagnosed with breast cancer should be strongly recommended a genetic test to reduce adverse consequences resulting from postponing the test and, if applicable, the preventive operation until later in life. Preventive surgery should be considered especially in BRCA1 gene mutation carriers previously treated for breast cancer because of the increased risk of ovarian cancer

Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer.

PURPOSE: This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. PATIENTS AND METHODS: Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks). RESULTS: A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm. CONCLUSION: Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.

[Features of pubescence in patients with pure gonadal dysgenesis in the course of a hormonally active tumor--case report]. / Cechy dojrzewania plciowego u pacjentek z czysta dysgenezja gonad w przebiegu hormonalnie czynnego guza--opis przypadków.

Germ cell tumors are the most frequent ovarian neoplasms among girls and young women under the age of 25. Female patients with gonadal dysgenesis are at higher risk of germ cell tumors. Two cases of women with pure gonadal dysgenesis were described. A hormonally active tumor secreting estrogens, caused the development of sexual features and genital tract bleeding what imitated premature puberty. It needs to be emphasized that the presence of sexual features does not exclude dysgenesis - a pathology that is connected with an increased risk of gonadal tumors--and that the ultrasound evaluation, during which the presence of follicles in gonads is evaluated, is essential.

Evaluation of serum levels of sCD30L ligand in patients with ovarian cancer in terms of selected clinico-pathological factors.

AIM OF THE STUDY: The CD30L ligand is a membrane-associated glycoprotein expressed by activated CD4(+)Th cells, macrophages, dendritic cells, and B lymphocytes. It binds to the CD30 receptor carried on activated and helper Th cells, inducing the immune response and apoptosis. The aim of this retrospective study was to determine the level of sCD30L in the serum of patients at diagnosis of ovarian cancer and at relapse and to assess the potential association of this ligand with selected clinico-pathologic factors. MATERIAL AND METHODS: We studied 69 patients with ovarian cancer allocated to two groups: A - ovarian cancer at diagnosis, B - relapse of ovarian cancer and active growth of the tumor. RESULTS: We found high levels of sCD30L in ovarian cancer patients. Levels at relapse (21.48 ng/ml) were significantly higher than at diagnosis (11.81 ng/ml). Poor response to first-line chemotherapy was accompanied by higher levels of sCD30L and by several other findings: resistance to platinum analogs was common, neoadjuvant chemotherapy was needed, relapse and death during two-year follow-up were frequent. CONCLUSIONS: Our present study might initially suggest that elevated concentration of sCD30L can be an important finding prognosticating a poor prognosis and is associated with platinum resistant and refractory cases of ovarian cancer. However, studies are needed on larger groups of patients.

[Isolated fallopian tube torsion in a teenager--a case report]. / Izolowany skret jajowodu u nastolatki--opis przypadku.

Adnexal torsion belongs to the group of urgent cases in gynecology Early diagnosis and management can prevent the loss of an ovary and the Fallopian tube. The case of the 14.5-year-old girl was described by the authors. The symptoms were moderate and caused diagnostics problems. During clinical assessment current literature knowledge, differentiation and treatment of the adnexa were taken into account.

Leptin levels in serum depending on Body Mass Index in patients with endometrial hyperplasia and cancer.

UNLABELLED: Leptin levels in serum depending on Body Mass Index (BMI) in patients with endometrial hyperplasia and cancer. OBJECTIVES: Concentrations of leptin, a hormone secreted by white adipose tissue, correlate strongly with body mass. Leptin interacts with several other hormones, modifies the activities of some enzymes and proinflammatory cytokines, participates in hematopoiesis, thermogenesis, and angiogenesis, and is involved in the control of carbohydrate and lipid metabolism. This study was undertaken to determine whether serum concentrations of leptin in obese patients with endometrial hyperplasia and cancer deviate from values in patients with normal endometrium. STUDY DESIGN: We enrolled 86 obese postmenopausal women, including 40 with endometrial cancer and hyperplasia and 46 with normal endometrium. Depending on BMI, three subgroups were formed: I<30; II = 30-40; III > 40. Leptin concentrations were measured with immunoenzymatic test kits from IBL. Statistical comparison was done with the chi square (chi(2)) test and Statistica software package. RESULTS: Mean serum concentration of leptin in endometrial cancer and hyperplasia was 16737.1 pg/ml as opposed to 9048.7 pg/ml in patients without endometrial pathology (p<0.0001). Significantly, higher concentrations of leptin were noted in every BMI subgroup of patients with endometrial pathology in comparison to controls (p<0.005). CONCLUSIONS: Leptin appears to participate in proliferative processes of the endometrium. Obesity is an important risk factor in endometrial cancer.

Tumors of dysgenetic gonads in Swyer syndrome.

BACKGROUND/PURPOSE: The female with Swyer syndrome requires close follow-up because of the high risk of neoplastic transformation in the dysgenetic gonads. The aim of this work was to present our experience with tumors in patients with Swyer syndrome. METHODS: We studied 8 females with Swyer syndrome. At the time of diagnosis, they were 13 to 18 years old. We performed an ultrasound examination of dysgenetic gonads, hormonal (follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone) and genetic (SRY, karyotype) tests, and histologic analysis of gonads (bilateral gonadectomy was performed in all patients). RESULTS: Gonadal tumors were found in 6 patients (3 cases of gonadoblastoma, 1 dysgerminoma, and 2 gonadoblastoma with dysgerminoma). Hormonal activity of gonadoblastoma was noted in 3 patients, with 1 tumor producing androgens. CONCLUSION: Our data suggest that patents with gonadal dysgenesis and 46,XY karyotype should be referred for bilateral gonadectomy because of the high risk of neoplastic transformation. Estrogen-producing gonadoblastoma may mask gonadal dysgenesis and delay the diagnosis of this pathology.

Premature menopause in patients with BRCA1 gene mutation.

This study was undertaken with regard to the gonadotropin theory of ovarian cancer advocated in the literature and was designed to disclose specific features of ovarian morphology in carriers of the BRCA1 gene mutation. We enrolled 171 patients and divided them into two groups: A (n=90)--operated for breast cancer (30 patients with and 60 without the BRCA1 mutation); B (n=81)--with the BRCA1 mutation qualified for preventive adnexectomy. According to the authors' classification described herein, some patients without the BRCA1 mutation retained "signs of estrogenization" in menopausal ovaries, revealing the role of estrogens as a factor promoting mammary carcinogenesis in these patients. A tendency to premature menopause was observed in BRCA1 mutation carriers of groups A and B as evidenced by the final menorrhea appearing at a younger age and almost total absence of "signs of estrogenization" in menopausal ovaries. It is concluded from these findings that earlier menopause in carriers of the BRCA1 mutation is associated with hypergonadotropic activity and may predispose to ovarian cancer at younger age.

Sex features at menarche in relation to gonadotropin, estradiol and sex hormone-binding globulin concentrations in girls with constitutional delay of puberty. Preliminary report.

OBJECTIVE: Constitutional delay of puberty (CDP) is the absence of secondary sexual features in otherwise healthy girls past the 13th year of life. The aim of the present work was to follow the development of estrogen-dependent sexual features, determine the concentrations of gonadotropins, estradiol and sex hormone-binding globulin (SHBG) in girls with CDP at menarche and compare the findings with normal controls. METHODS: We enrolled 11 girls with CDP and 40 controls. Primary, secondary and tertiary sexual features were studied at menarche +/- 3 months. The size of the ovaries and uterus was measured using transabdominal ultrasound. Maturation of breasts and pubic hair was staged according to Tanner. Concentrations of gonadotropins (follicle-stimulating hormone (FSH), luteinizing hormone) and estradiol were measured with immunoenzymatic methods. For measurement of SHBG, a radioimmunoassay was applied. RESULTS: Menarche in CDP girls usually appeared with Stage IV or V of breast development and Stage IV of pubic hair development according to Tanner. CDP girls demonstrated a significantly smaller volume of the uterine body at menarche compared with controls (p = 0.0004). Significantly lower levels of FSH (p = 0.0363) and estradiol (p = 0.0332), as well as a tendency towards lower levels of SHBG, were revealed in CDP girls at menarche. CONCLUSION: In CDP girls, menarche is accompanied by more mature tertiary sexual features, apparently resulting from longer exposure of estrogen-dependent tissues to the action of bioactive endogenous estrogens. The smaller volume of the uterine body in CDP girls at menarche may be attributed to decreased concentrations of FSH and estradiol, as well as to the possibility of decreased insulin-like growth factor-1 and increased neuropeptide Y levels.

Ovarian cystadenoma as a characteristic feature of families with hereditary ovarian cancers unassociated with BRCA1 and BRCA2 mutations.

The study aimed to determine whether hereditary ovarian cancers that are not caused by BRCA1/BRCA2 constitutional mutations are associated with a predisposition to cystadenoma. The study consisted of two parts. Part one concerned the incidence of ovarian cystadenoma in females from families with hereditary ovarian cancer unassociated with BRCA1 mutations. The study group included 62 female patients from 29 families, without any previously diagnosed malignancy, with no proven constitutional mutation of the BRCA1 gene. The first control group was composed of 62 female patients from 53 families, without any previously diagnosed malignancy, with an identified constitutional mutation of the BRCA1 gene. The second control group comprised 124 female patients for whom the only reason for the examination was a prophylactic check-up. All studied women were subjected to intravaginal ultra- sonographic investigations. In 8 patients with benign and/or borderline ovarian cystadenoma, a complete sequencing of coding fragments of the BRCA2 gene from the peripheral blood DNA was performed. Part two of this study concerned the incidence and pattern of malignant tumors in the families of female patients with ovarian cystadenoma. The final study group included 117 patients who had 726 I0 relatives (359 females and 367 males). We concluded that cystadenoma is likely to be a characteristic feature of the subgroup of families with hereditary ovarian cancers unassociated with BRCA1/BRCA2 constitutional mutations.

Gonadotropin (LH, FSH) levels in serum and cyst fluid in epithelial tumors of the ovary.

OBJECTIVES: The aim of this work was to determine gonadotropin (LH, FSH) levels in serum and cyst fluid in various type of ovarian epithelial neoplasms (benign, borderline, malignant) and to compare them with levels in benign cysts. Additionally we decided to estimate if there were some significant correlations between serum and ovarian cyst fluid in gonadotropin levels in all investigated groups. MATERIALS AND METHODS: The study group included 74 patients before (n=36) and after (n=38) menopause, divided into four groups depending on the histopathologic diagnosis. Serum and cyst fluid levels of LH and FSH were determined in all patients. RESULTS: We found statistically significant differences concerning LH and FSH levels in serum and cyst fluid between malignant and borderline tumors, between malignant tumors and benign cystadenomas and between malignant tumors and non-neoplastic cysts. We also found statistically significant correlations between serum and cyst fluid as to FSH and LH levels in patients with borderline tumors. There were no statistically significant correlations between serum and cyst fluid as to FSH and LH levels in patients with malignant epithelial tumors (group 1) and in patients with benign cystadenomas (group 3). CONCLUSIONS: High FSH and LH levels in cyst fluid of malignant epithelial tumors of the ovary are in line with the gonadotropin theory of tumor growth. Simultaneous determination of various types inhibin levels appears to be an interesting topic for our future research.

[Granulosa cell tumor in different periods of women's life]. / Ziarniszczak w róznych okresach zycia kobiety.

UNLABELLED: Ovarian granulosa cell tumor is uncommon malignancies. By virtue of histopathological examination we distinguish two subtype of GCT: adult type granulosa cell tumor typically in older women and juvenile granulosa cell tumor recognized primarily in children and young adults. GCTs behave unpredictably. Depending on histological type patients suffer recurrences in different time after treatment, even many years from diagnosis. OBJECTIVES: The aim of our study is clinical analysis of patients with AGCT and JGCT, especially the problem of choice of treatment, time to occurring recurrences and new possibility in long term follow up. MATERIAL AND METHODS: We analyzed 22 patients treated in Department of Gynecological Surgery and Oncology of Adults and Adolescent Pomeranian Academy of Medicine and then observed in our outpatient clinic. RESULTS: Among analyzed 22 patients 18 had adult type of granulosa cell tumor, mean age of these women was 47 years (32-72). Juvenile type of granulosa cell tumor were recognized in 4 patients and they were from 4 to 7 years old. All young girls were underwent sparing surgery, one of them was treated with radiotherapy. In histopathological examination of 4 years old girl atypia and a lot of mitosis was observed and she was treated with chemotherapy. Unfortunately after 18 months from diagnosis she died due to very dynamic recurrence. Remained 3 girls live without evidence of disease and the longest time of follow up is 36 years. 16 women with AGCT were underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy, 2 were performed conservative surgery because they wish to preserve their fertility. 16 patients were treated with radiotherapy as an adjuvant treatment, two additionally with GnRH analogues. Recurrences in patients with AGCT were recognized in 5 cases. Mean time to recurrence from diagnosis were 11.7 years. In two patients it happened after 21 and 22 years. Despite of aggressive chemotherapy four of these patients died during one year. Remained 13 women with adult granulosa cell tumours live without evidence of disease and the longest time of observation is 9 years. In histopathological examination of all patients who died were describe cellular atypia and high mitotic rates. During long time follow up our patients were performed second-look laparoscopies, tested of estradiol levels and 5 of them also inhibin B levels which always correlated with actual condition. CONCLUSION: Granulosa cell tumor is ovarian neoplasm of different behaviour. Patients with this diagnosis should be monitoring for many years. Inhibin is valuable examination in long term follow up.

[Germinal cell tumors in young and adolescent girls]. / Nowotwory germinalne u dziewczat i mlodych kobiet.

OBJECTIVE: Germ cell tumours are the most common ovarian tumours in childhood and adolescence. This diverse group of tumours derives from germ cells. DESIGN: The aim of this work is presentation of germ cell tumours in the material from our clinic with characteristic clinical features, the scope of operation and effects of many years of observation. MATERIALS AND METHODS: We treated 109 girls with germ cell tumours of the ovary: 13 had malignant tumours: there were 7 patients with dysgerminomas, 2 with endodermal sinus tumour of the ovary, 3 with immature teratomas, 1 with carcinoma embryonale. Gonadoblastomas was diagnosed 4 patients and mature teratomas in 92 patients. RESULTS: 11 patient had gonadal dysgenesia with abnormal karyotype. These girls had no follicle apparatus in gonads and had elevated levels of gonadotropins. Gonadoblastoma is almost always found in patients with gonadal dysgenesis. Gonadoblastoma often produces estradiol or testosterone. There can be problems with diagnosis of the syndrome, because developmental features imitate the onset of normal puberty. Most patients with dysgerminoma have stage I of disease and surgery is sufficient. It must be suggested that patients of stage I who wish to preserve childbearing function may be treated with unilateral salpingoophorectomy and adjuvant chemotherapy. Monitoring of the treatment is connected with measurement of biochemical markers. Some of these markers are useful for monitoring of response to therapy. When levels of markers are low second look laparoscopic operation should be performed. Cytological smears and biopsy specimens from the remaining ovary, peritoneum and subdiaphragmatic area should be obtained laparoscopically. CONCLUSIONS: The sift ultrasonographic investigations can be helpful in the early diagnosis of germ cell tumours of the ovary in girls. Absence of follicle apparatus in the gonads requires determination of levels of gonadotropins and karyotype. Fertility sparing operative treatment is preferred when karyotype is normal.

Growth hormone, IGF-1, insulin, SHBG, and estradiol levels in girls before menarche.

The timing of pubertal changes depends on the concerted function of the hypothalamic - pituitary - ovarian and other endocrine systems. The somatotropin system and insulin play important roles during the growth and maturation of girls. Our clinical observations have enabled us to determine and implement criteria that split the pre-menarcheal period into three phases with distinct features associated with rising levels of estrogens (pre-estrogenization, onset of estrogenization and full estrogenization). The aim of this work was to determine levels of growth hormone, insulin - like growth factor 1 (IGF-1), sex hormone binding globulins (SHBG), insulin, and estradiol in relation to somatic features in girls during subsequent phases of estrogenization. This prospective study was done in 45 healthy girls. Every three months, we recorded weight, height, BMI, maturation of tertiary sex features, estrogen-related changes in hymen, sonographic dimensions of ovaries and uterus and serum levels of growth hormone, IGF-1, SHBG, insulin, and estradiol. Onset of estrogenization was accompanied by reduction of body mass and slowing down of growth associated with declining levels of growth hormone. These changes were followed by weight gain, pubertal acceleration of growth, rising levels of growth hormone, IGF-1, insulin, and estradiol, and falling levels of SHBG.

Hereditary ovarian cancer in Poland.

There is increasing evidence that hereditary factors play a greater role in ovarian cancer than in any of the other common cancers of adulthood. This is attributable, to a large extent, to a high frequency of mutations in the BRCA1 or BRCA2 genes. In Poland, 3 common founder mutations in BRCA1 account for the majority of families with identified BRCA mutations. Our study was conducted in order to estimate the prevalence of any of 3 founder BRCA1 mutations (5382insC, C61G and 4153delA) in 364 unselected women with ovarian cancer, and among 177 women with ovarian cancer and a family history of breast or ovarian cancer. A mutation was identified in 49 out of 364 unselected women with ovarian cancer (13.5%) and in 58 of 177 women with familial ovarian cancer (32.8%). The majority of women with ovarian cancer and a BRCA1 mutation have no family history of breast or ovarian cancer. The high frequency of BRCA1 mutations in Polish women with ovarian cancer supports the recommendation that all Polish women with ovarian cancer should be offered testing for genetic susceptibility, and that counseling services be made available to them and to their relatives. It is important that mutation surveys be conducted in other countries prior to the introduction of national genetic screening programs.