Cem Baykal

Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas

OBJECTIVE The purpose of this study is to evaluate the significance of the c-Met/hepatocyte growth factor receptor expression in invasive cervical carcinoma. METHODS Ninety-Four patients with FIGO stage 1B disease, treated primarily with surgery, were studied immunohistochemically. Of the cases, 67 were squamous carcinoma and 27 were nonsquamous (10 were adenocarcinoma, 15 were adenosquamous carcinoma, and 2 were indifferentiated carcinoma). Immunohistochemically stained c-Met slides of primary malignancies were evaluated blindly of clinical outcome and other histopathological factors. RESULTS Overexpression of c-Met was found in 56 of 94 specimens. Primary tumors which show recurrences were found to be c-Met overexpressors. Univariate survival analysis (Kaplan-Meier) showed that c-Met overexpression is significantly correlated with disease-free survival. Moreover the diameter of the primary tumor, deep cervical stromal invasion, presence of metastatic lymph node, number of metastatic lymph nodes and c-Met overexpression were significantly correlated with overall 5-year survival. Furthermore multivariant analysis with Cox regression showed that the presence of metastatic lymph node and immunopositivity for c-Met are significantly correlated with overall survival, while c-Met overexpression was found to be an independent variable for disease-free survival. CONCLUSION These results reveal that c-Met oncogene overexpression is an important parameter for disease progression, recurrence, and survival in early-stage invasive uterine cervix carcinomas.

Primary choriocarcinoma of the uterine cervix in a postmenopausal patient: a case report.

BACKGROUND Primary cervical choriocarcinoma seen in a postmenopausal patient is a very rare entity. CASE Primary choriocarcinoma of the uterine cervix was diagnosed in a 54-year-old woman. She had admitted to our clinic with vaginal bleeding and had been postmenopausal for 1 year at the time of diagnosis. A cervical tumoral mass was seen in her pelvic examination and cervical biopsy revealed squamous cell carcinoma of the cervix. Pelvic examination under anesthesia was done and patient was accepted as FIGO Stage IIA. Type III hysterectomy with bilateral salphingoopherectomy and bilateral pelvic-paraaortic lymph node dissection was carried out. Postoperative pathological evaluation of the surgical specimen showed that case was a primary choriocarcinoma of the cervix. CONCLUSION This is one of the few reported cases of cervical choriocarcinoma in a postmenopausal patient. The most appropriate theory for the development of this tumor is metaplastic differentiation of the tumor from another histologic type.

Effects of hormone replacement on hemostasis in spontaneous menopause.

Objective To examine the effects of continuous combined estrogen-progesterone replacement therapy on coagulation and natural anticoagulant systems in spontaneous menopause. Design A randomized, double-blind, placebo-controlled study was conducted during a 6-month period to examine the effect of hormone replacement therapy (HRT) on blood coagulation parameters. One hundred-ten healthy postmenopausal women were randomized into two groups. Those in group 1 were given conjugated estrogen (0.625 mg/d, Premarin) and medroxyprogesterone acetate (5 mg/d, Farlutal), and those in group 2 were given identical tablets of placebo for 6 months. Serum levels of modified activated protein C resistance, antithrombin III, fibrinogen, factor VIIa, factor VIII, factor IX, activated partial thromboplastin time, prothrombin time, thrombin time, and lipoprotein (a) were measured before and 6 months after the treatment and analyzed for changes in extrinsic and intrinsic coagulation parameters. Results At the end of the 6-month period, fibrinogen, lipoprotein (a), and activated protein C resistance levels were decreased significantly in the HRT group compared with the control group. Antithrombin III levels were increased, indicating antithrombin activity. Activated partial thromboplastin time, as a measure for intrinsic coagulation cascade, was prolonged in concert with decreased intrinsic coagulation factors, factor VIII, and factor IX (p < 0.05). In the extrinsic coagulation system, prothrombin time was significantly increased, although factor VIIa level was not changed (p > 0.05). Conclusion Significant changes were observed in the coagulation parameters, which may further explain the cardioprotective effect of HRT.

Does Aquaporin-1 expression have clinical significance in serous epithelial ovarian cancer?

OBJECTIVE To assess the relationship between Aquaporin-1 (AQP1) expression and clinicopathological variables in serous epithelial ovarian cancer (EOC). MATERIAL AND METHODS Serous EOC cases treated in our institution between January 2007 and December 2009 were included in the study. A semi-quantitative immunohistochemical method was used to determine AQP1 expression levels, intratumoral microvessel density (IMD) and AQP1/IMD ratios. The relationship between these parameters and clinicopathological variables were assessed. P values less than 0.05 was considered statistically significant. RESULTS A total of 55 cases of serous EOC were included in the study. AQP1 was strongly expressed in the membranes of microvessels and small vessels within all tumor tissues. In a few cases, AQP1 expression was also observed in the membrane of interstitial cells and in individual tumor cells. A positive correlation was detected between preoperative CA125 levels and the expression of AQP1 (R: 0.277, p<0.05). AQP1 expression was similar between FIGO stage I-II and FIGO stage III-IV cases (p > 0.05). A significant relationship did not exist between AQP1 expression and FIGO stage, lymph node metastasis or ascites volume (p>0.05). CONCLUSION In this study, AQP1 expression did not have a significant association with important clinicopathological variables in serous EOC. Future studies are needed to determine AQP1 expression in other histological types of EOC.

Expression of Hepatocyte Growth Factor/ Scatter Factor Receptor in IUGR Fetuses' Placentas: An Immunohistochemical Analysis

Objective: We aimed to evaluate the expression sta tus of c-met, receptor for the hepatocyte growth factor (HGF), in the placentas of intrauterine growth retardation (IUGR) fetuses. Materials and Methods: Placentas were obtained during delivery from both third trimester normal and IUGR complicated pregnancies. Ultrasonographic estimation of fetal birth weight has been done and placentas of those under the fifth percentile for their gestational ages were enrolled in the study group. Eighteen fetuses with IUGR and 6 uncomplicated pregnancies were subjected to the study. Histological sections from placentas were immunohistochemically evaluated for the expression status of c-met. Results: Seventeen of the eighteen patients (94.4%) in the study group were found to have overexpression of the c-met while this figure was only 16.7% (1/6) in the control group (p < 0.0001). There was a strong statistically significant difference between the two groups regarding degree of c-met expression. Conclusion: Our present findings suggest that c-met is an important cell membrane receptor in human placenta. Deregulation of the interaction between HGF and its receptor c-met during placentation may be the cause responsible for the growth retardation of the fetus due to the impaired placental functions.

Topotecan induced nail pigmentation.

A 66-year-old woman with serous papillary ovarian carcinoma developed hyperpigmentation of the nails while she was being treated with topotecan at three week intervals. Topotecan is a semi synthetic analogue of camptothecin that inhibits topoisomerase 1. This case is the first in the literature discussing the nail toxicity of topotecan. Camptothecin analogues like topotecan and irinotecan are effective chemotherapeutic drugs used in the treatment of solid tumors. Topotecan is used mainly in small cell lung cancer and epithelial ovarian cancer (1). Ongoing trials are evaluating its usage in cervical and uterine carcinomas (2, 3). Topotecan is administered as intravenous infusion lasting five days every three weeks. Nail changes have been reported to be caused by other commonly used chemotherapeutics in gynecologic oncology. Cyclophosphamide (4), taxanes (5), hydroxyurea (6), capecitabine and irinotecan (7) are all known to effect nails. We report the first case in the English literature in which complete nail discoloration developed while using topotecan as single agent therapy against epithelial ovarian cancer. Case: A 66-year-old woman was admitted to our clinic with the complaints of postmenopausal bleeding and abdominal distension. A computed tomography was done, and ascites in the abdomen was found together with a left adnexial mass of 10 cm. in diameter. There were also metastatic lesions on the surface of the liver. CA 125 value was 625 U/ml. After preoperative evaluation, the patient was operated on. FIGO Stage IIIc serous papillary ovarian carcinoma was diagnosed, and the diagnosis was confirmed pathologically. Optimal debulking was carried out. Two weeks after the operation, an adjuvant chemotherapy regimen consisting of paclitaxel and cisplatin was initiated, and patient received this regimen for six courses once, every three weeks. After complete response she was followed up at three month intervals. Six months after the completion of the first line chemotherapy, the CA 125 value was found to be altered, and a recurrent abdominal tumor was diagnosed by tomography. A second line chemotherapy consisting of intravenous topotecan (1.25 mg/m/day) five days every three weeks was planned and initiated. The patient complained of a color change in her fingernails at the beginning of the 4th course of chemotherapy. She was evaluated by a dermatologist colleague, and this hyperpigmentation was diagnosed as an adverse effect of topotecan. She was not receiving any other drugs in that time period. Continuation of the therapy was decided because of the well being of the patient. She is still receiving the last course of the chemotherapy. Conclusion: The various chemotherapeutic agents listed above are well known to cause nail pigmentation. This toxicity may begin after an interval of weeks or months and usually regresses after the discontinuation of the causative agent. Splinter hemorrhage, subungual hematoma, Beau lines, acute paronychia, and onycholysis are the other ungual toxicities that can be seen in patients receiving chemotherapeutics. The National Cancer Institute describes two grades of nail changes. Grade 1 includes discoloration, ridging or pitting of the nail. Grade 2 includes partial or complete loss of the nail or pain in the nail bed. The pathogenesis of this Grade 1 nail toxicity (pigmentation) may include genetic predisposiThe Journal of Dermatology Vol. 31: 951–952, 2004 Fig. 1. Nails demonstrating brownish discoloration and periungual erythema

Twin pregnancy after ICSI in a patient with ovarian cancer complicated with maternal hepatitis C: case report

Fertility sparing surgery was carried out for an epithelial ovarian cancer patient. After adjuvant chemotherapy, she underwent assisted reproduction and gave birth to twins. She was given alpha-Interferon therapy for hepatitis C during pregnancy.

Ovarian pregnancy with intrauterine device in situ.

IntroductionSince some reports have already suggested a higher rate of ovarian pregnancies in women using intrauterine device and some have not, an additional case report may be of interest for the literature purposes.Case reportIn this case report we present an ovarian pregnancy in a patient with an intrauterine device in situ.

Fixed Drug Eruption of the Penis due to Zolmitriptan

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