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R Halperin

Publications and source records attributed to R Halperin.

At least 19 recordsLinked to original sources
PubMed2005

Development of a tissue-engineered composite implant for treating traumatic paraplegia in rats.

This study was designed to assess a new composite implant to induce regeneration of injured spinal cord in paraplegic rats following complete cord transection. Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of human origin, or spinal cords of human embryos, were cultured in two consecutive stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in suspension on positively charged microcarriers (MCs). A tissue-engineered tubular scaffold, containing bundles of parallel nanofibers, was developed. Both the tube and the nanofibers were made of a biodegradable dextran sulphate-gelatin co-precipitate. The suturable scaffold anchored the implant at the site of injury and provided guidance for the regenerating axons. Implants of adult human NOM cells were implanted into eight rats, from which a 4 mm segment of the spinal cord had been completely removed. Another four rats whose spinal cords had also been transected were implanted with a composite implant of cultured human embryonic spinal cord cells. Eight other cord-transected rats served as a control group. Physiological and behavioral analysis, performed 3 months after implantation, revealed partial recovery of function in one or two limbs in three out of eight animals of the NOM implanted group and in all the four rats that were implanted with cultured human embryonic spinal cord cells. Animals of the control group remained completely paralyzed and did not show transmission of stimuli to the brain. The utilization of an innovative composite implant to bridge a gap resulting from the transection and removal of a 4 mm spinal cord segment shows promise, suggesting the feasibility of this approach for partial reconstruction of spinal cord lesions. Such an implant may serve as a vital bridging station in acute and chronic cases of paraplegia.

Animals↗
PubMed2004

Ectopic pregnancies in a Caesarean scar: review of the medical approach to an iatrogenic complication.

Implantation of a pregnancy within a Caesarean fibrous tissue scar is considered to be the rarest form of ectopic pregnancy and a life-threatening condition. We conducted a computer search of the English literature of all studies since 2002 to gather updated data on the outcome of such pregnancies. Sixty-six new cases were reported since 2002, possibly reflecting the increasing number of Caesareans currently being performed as well as the more widespread use of the transvaginal scan allowing their earlier detection. Analysis of these women's obstetric history revealed that those at risk for pregnancy in a Caesarean scar appear to have a history of dilatation and curettage, placental pathology, ectopic pregnancy, and IVF. Twenty-one out of 39 for which this information was available (54%) had undergone multiple (> or =2) Caesareans and 13 had previous dilatation and curettage, which might also be an associated factor. We review and discuss the features of contemporary work-ups, including a high index of awareness, a detailed history and a skillful ultrasound examination for an early and accurate diagnosis. Healthcare professionals should be familiar with the possibility of untoward sequelae and how a modern work-up can help in guiding conservative options, thus reducing morbidity and preserving fertility.

Cesarean Section↗
PubMed2004

Drug development for ovarian hyper-stimulation and anti-cancer treatment: blocking of gonadotropin signaling for epiregulin and amphiregulin biosynthesis.

Gonadotropins play a crucial role in ovarian homeostasis and fertilization through the activation of the cAMP cascade. However, gonadotropin hyper-stimulation may be associated with higher risk for ovarian cancer development. It has been suggested, that high gonadotropin levels in peritoneal and ovarian cystic fluids of patients suffering from benign ovarian cysts, may lead to malignancy. Moreover, we have recently discovered that gonadotropin stimulation can activate the MAPK cascade in target cells. Using DNA microarray technology and RNA from human granulosa cells, we discovered that stimulation with saturating doses of gonadotropins dramatically elevates activity of genes coding for epiregulin and amphiregulin. These gene products can bind and activate the EGF receptor and ERBB4, which are associated with the development of various cancers such as ovarian, breast endometrial and other non-gynecological malignancies. Gonadotropin receptors are expressed not only in the gonads, but also in non-gonadal tissues and in cancer cells. The discovery that gonadotropins activate certain mitogenic signal transduction pathways, may serve as a guide for novel anti-cancer therapy by (1) specific interference at the receptor level to block the gonadotropic response, or arresting the receptor expression and (2) blocking downstream mitogenic signals generated by these hormones, like attenuation of the expression of epiregulin and amphiregulin that belong to the EGF family, using anti-sense and/or SiRNA techniques targeted to suppress their expression. Moreover, since amphiregulin and epiregulin act as mediators of luteinizing hormone (LH) action in the mammalian ovulatory follicles, regulation of the expression of these factors may open new possibilities in treatment of ovarian malfunction implicated with ovarian hyper-stimulation.

Amphiregulin↗
PubMed2004

Ectopic pregnancies in Caesarean section scars: the 8 year experience of one medical centre.

BACKGROUND: Our aim was to supplement the mostly individual case reports on the rarely occurring and life-threatening condition of ectopic pregnancy developing in a Caesarean section scar. METHODS AND RESULTS: Eight of all the patients treated in our department between 1995 and 2002 had been diagnosed for ectopic pregnancy that developed in a Caesarean section scar. They comprised this case series group. Four of them underwent methotrexate treatment; one had expectant management, one transcervical aspiration of the gestational sac and two by open surgery. All the non-surgically treated women had an uneventful outcome. One underwent a term Caesarean hysterectomy and the other first trimester hysterotomy and excision of the pregnancy located in the scarred uterus. Analysis of all these women's obstetric history revealed that five of them (63%) had been previously operated because of breech presentation, one had a cervical pregnancy and one had placenta previa. Four of them (50%) had multiple (> or = 2) Caesarean sections. CONCLUSIONS: The women at risk for pregnancy in a Caesarean section scar appear to be those with a history of placental pathology, ectopic pregnancy, multiple Caesarean sections and Caesarean breech delivery. Heightened awareness of this possibility and early diagnosis by means of transvaginal sonography can improve outcome and minimize the need for emergency extended surgery.

Adult↗
PubMed2004

Pathological characteristics of ovarian cancer occurring after hysterectomy.

OBJECTIVE: The aim of the current study was to examine the pathological characteristics of ovarian cancer occurring in women with previous hysterectomy. METHODS: Newly diagnosed cases of ovarian primary epithelial or primary peritoneal cancer, operated on in our department between January 2000 and December 2002, were included in this retrospective study. The patients were divided into two groups, group I included eight patients with ovarian cancer and previous hysterectomy, and group II comprised 70 patients with ovarian or primary peritoneal cancer, but without previous hysterectomy. RESULTS: There was no significant difference between the eight patients with ovarian cancer and previous hysterectomy and the 70 patients without previous hysterectomy considering the patients' characteristics. Conversely, there was a difference between the two study groups regarding the histology of the tumor, its grade and the stage of the disease. All patients with ovarian cancer and previous hysterectomy had poorly differentiated mixed epithelial or undifferentiated tumors. Nevertheless, only 25% of these patients were diagnosed in Stage IIIC. CONCLUSION: It seems that besides reducing the risk of further ovarian cancer, hysterectomy also causes a change in the main histological sub-group of ovarian cancer, that develops in patients with previous hysterectomy. The greatest protective effect was observed for serous ovarian tumors.

Carcinoma↗
PubMed2003

Luteinizing hormone in peritoneal and ovarian cyst fluids: a predictor of ovarian carcinoma.

OBJECTIVE: The aim of this study was to define the role of luteinizing hormone (LH) as a tumor marker, specific for ovarian cancer. METHODS: The study included 34 women with functional and benign ovarian cysts, 11 women with borderline ovarian tumors, 22 patients with advanced ovarian cancer and 15 patients with non-ovarian intraperitoneal malignancies. Serum, peritoneal fluid and ovarian cyst aspirates were obtained intraoperatively (laparoscopy or laparotomy) and were subjected to the LH analysis. RESULTS: Peritoneal fluid LH levels were significantly increased in patients with ovarian cancer and those with borderline ovarian tumors as compared to patients with functional and benign ovarian cysts (P=0.005 and P=0.007, respectively). The patients with non-ovarian malignancies demonstrated the same peritoneal fluid LH levels as patients with benign ovarian tumors. There was no significant difference in the level of peritoneal fluid LH between ovarian cancer patients with and without ascites. The patients with functional and benign ovarian cysts demonstrated also significantly lower cyst fluid LH levels as compared to patients with malignant and borderline ovarian cysts (P=0.01 and P=0.03, respectively). Peritoneal and ovarian cyst fluid levels of LH were significantly increased in patients with fibrothecomas as compared to patients with other benign ovarian cysts. There were no significant differences in the serum LH levels comparing patients from all study groups. CONCLUSION: LH, detectable in peritoneal and ovarian cyst fluids, can be used as a tumor marker for identification of patients with borderline and malignant ovarian tumors.

Ascitic Fluid↗
PubMed2003

Prevention of genital prolapse following Burch colposuspension: comparison between two surgical procedures.

Our objective was to evaluate the efficacy of cul-de-sac obliteration in preventing pelvic floor anatomical defects formation following Burch colposuspension. We evaluated 441 patients who had undergone Burch colposuspension. The patients were divided into two groups: group A (132 patients) who underwent Burch colposuspension only, and group B (309 patients) who had had a concomitant cul-de-sac obliteration. Cul-de-sac obliteration was performed using two different techniques, the Moschocowitz procedure in 131 patients, and approximation of the sacrouterine ligaments in 178 patients. The follow-up period was 8.6 years (range 3-16). In total we found 43/441 (9.7%) postoperative anatomical defects. Obliteration of the cul de sac significantly (P<0.0001) reduced the formation of anatomical defects compared to Burch colposuspension. In a comparison of the two surgical procedures for cul-de-sac obliteration, the approximation of the sacrouterine ligaments was significantly more effective than either the Moschcowitz procedure (P<0.001) or the Burch colposuspension alone (P<0.001). The Moschcowitz procedure reduced the formation of anatomical defects to 15/131 (11.4%) compared to Burch colposuspension only (25/132; 18.9%), but statistically the difference was insignificant. The time of anatomical defect detection was significantly reduced after cul-de-sac obliteration: 2 years 6/25 (24%) in group A compared to 1/8 (5.5%) in group B (P<0.01). After 5 years the detection rate was 64% (16/25) and 22.2% (4/18) respectively (P<0.01). It was concluded that cul-de-sac obliteration using approximation of the sacrouterine ligaments significantly reduced the incidence of anatomical defect formation following Burch colposuspension. A long follow-up period is needed to evaluate the truce incidence.

Douglas' Pouch↗
PubMed2003

Pathological findings in early-stage endometrial cancer.

OBJECTIVE: The aim of this study was to assess the pathological characteristics of early-stage endometrial cancer, with regard to endometrioid versus serous papillary adenocarcinoma. METHODS: Sixty-six cases of early-stage endometrial carcinoma were classified into two groups: group I--36 cases of endometrioid endometrial cancer, staged IA-IB and graded G1-G2; group II--30 cases of Stage I serous papillary endometrial cancer. The pathological characteristics compared between the two groups included features such as tumor location in the uterine cavity, tumor focality, lymphovascular invasion, as well as the status of the uninvolved endometrium, adjacent to the tumor. Patient clinical characteristics were obtained from the medical records. RESULTS: Significantly more patients with endometrioid endometrial cancer were premenopausal (p < 0.0001), obese (p < 0.02), had hypertension (p < 0.00001) and familial cancer (p < 0.0001). On the other hand, significantly more patients with serous papillary cancer had another primary malignancy (p < 0.001). Considering the pathological characteristics, 75% of endometrioid as compared with 6.7% of serous papillary cancer cases were found in the upper uterine segment only (p < 0.0001). Multifocality was observed in 16.7% of endometrioid as compared with 100% of serous papillary cancer cases (p < 0.0001). Lymphovascular space invasion was absent in all cases of endometrioid cancer, while present in 90% of serous papillary cancer cases (p < 0.0001). Seventy-five percent of endometrioid and 100% of serous papillary cancer cases were associated with an atrophic endometrium. CONCLUSION: The clinical and pathological features of early-stage endometrial cancer differ according to the histological type of the cancer. The majority of endometrioid cancers are probably associated with an atrophic or normally cycling endometrium, and not with endometrial hyperplasia.

Aged↗
PubMed2002

Laminaria dilatation and evacuation for pregnancies with mid-trimester premature rupture of membranes: a retrospective cohort study.

OBJECTIVE: To assess the efficacy and risk of chorioamnionitis with laminaria tents and uterine evacuation in patients with mid-trimester premature rupture of membrane (MPROM). STUDY DESIGN: A retrospective cohort study of 34 women, admitted between January 1995 and May 1999 with confirmed mid-trimester (14-23 weeks) PROM and 34 controls matched for gestational age, undergoing elective termination. All women underwent cervical dilatation by the use of laminaria tents followed by uterine evacuation (D approximately equals E). Perioperative complications were retrieved from the medical records and long-term ones by telephone questionnaire. RESULTS: Apart from one case requiring a change in antibiotic, no short- or long-term complications were reported. Although, in 8 out of 19 study cases (42%) endocervix culture was positive. The number of laminaria tents used was similar in both groups. The future pregnancy rate was higher in the study group but included four early spontaneous abortions and one ectopic pregnancy. CONCLUSION: Evacuation of uterus following cervical dilatation by laminaria tents in patients presenting with MPROM is safe, and probably not associated with future adverse pregnancy outcome.

Abortion, Induced↗
PubMed2002

Uterine papillary serous carcinoma (pure and mixed type) compared with moderately and poorly differentiated endometrioid carcinoma. A clinicopathologic study.

OBJECTIVE: The aim of this study was to investigate the clinicopathologic features and the outcome in patients with pure and mixed type uterine papillary serous carcinoma (UPSC), and to compare these parameters with those observed in patients with moderately and poorly differentiated endometrioid endometrial carcinoma (MPD-EEC). METHODS: The charts of 34 patients with UPSC and 30 patients with MPD-EEC, operated on between January 1995 and December 2000, were retrospectively reviewed. The UPSC group included ten cases of pure and 24 cases of mixed type UPSC (admixed with endometrioid component). All patients had undergone full surgical staging. Clinical features, surgicopathological findings, recurrence rate and recurrence-free interval were compared between the study groups. RESULTS: Significantly more patients with MPD-EEC than with UPSC were operated on in FIGO stage I and II (p = 0.001). MPD-EEC patients were significantly older and more obese (p = 0.03 and p = 0.01, respectively) as compared with the UPSC patients. Significantly more patients with MPD-EEC presented with postmenopausal bleeding (p = 0.02), had a second primary cancer in the past (p = 0.03) and had a first degree relative with history of malignant disease (p = 0.0001). Conversely, the rates of positive abdominal cytology and cervical involvement were significantly higher in the group of UPSC (p = 0.02 and p = 0.02, respectively). Significantly more patients with UPSC were treated with adjuvant therapy (p = 0.01). No significant difference between the two study groups was observed comparing the recurrence rate, the recurrence free interval and the 3-year survival. There was also no significant difference between the pure and the mixed type UPSC, considering the clinical features and the follow-up data. CONCLUSION: The current study presented no significant difference in the outcome of MPD-EEC as compared with the pure and the mixed type UPSC, yet prospective studies are needed to evaluate the role of adjuvant therapy in each study group.

Aged↗
PubMed2001

The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeli women with endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is considered a hormonal-dependent tumor; estrogen induces endometrial cellular proliferation, whereas progestins display an antiproliferative effect on endometrial tissue. The role that androgen and its receptor (androgen receptor [AR]) play in the pathogenesis of endometrial carcinoma is less clear. Although androgen has an in vitro inhibitory effect on endometrial cell proliferation, up to 75% of endometrial carcinoma express AR somatically. A polymorphic CAG repeat within exon 1 of the AR encodes for a polyglutamine tract, with length range of 8 to 33 repeats, which is inversely correlated with the transcriptional activity of the AR. METHODS: To gain insight into the role of AR in endometrial carcinoma, the authors analyzed the polymorphic CAG repeat in 79 Jewish Israeli patients with endometrial carcinoma as compared with 44 healthy Jewish women serving as controls. Analysis was conducted using germline DNA as template and using polymerase chain reaction primers flanking the CAG repeat with subsequent fluorescent determination of allele sizes. RESULTS: Allele size range of the longer of the two alleles in the patients was 11-33 (mean, 19.8 +/- 2.7) and in the controls 10-22 (mean, 17.9 +/- 1.9), a statistically significant difference (P < 0.01). Allele size variation within the patient group did not correlate with disease stage, grade, reproductive history, or age at diagnosis. CONCLUSIONS: The authors conclude that AR-CAG repeat length differs in Jewish patients with endometrial carcinoma as compared with healthy individuals in Israel, and this finding increases the possibility that the AR is involved in the predisposition to this neoplasm.

Aged↗
PubMed2001

Held-breath self-gating technique for radiotherapy of non-small-cell lung cancer: a feasibility study.

PURPOSE: To examine the feasibility of a held-breath self-gating (HBSG) technique in the radiotherapy of lung cancer. MATERIAL AND METHODS: Sixteen consecutive eligible and consenting patients undergoing radiotherapy for non-small-cell lung cancer were accrued for this study. The patients underwent a standardized training session and were then asked to breath hold at four points in the breathing cycle (maximal and end tidal, inspiration and expiration) while under fluoroscopic visualization. Plain films and video imaging with digital image analysis were used to record and measure the movement of the diaphragm, a tumor surrogate, in the superior-inferior axis. These measurements were obtained during and between multiple separate breath holds within one session and between breath holds in sessions held at least one day apart. RESULTS: Maximal inspiration and expiration tend to provide the best positional reliability, and the standard deviation of diaphragmatic position ranged from 0.13 to 2.57 mm, with an average of 0.97 mm. During a single breath hold, the diaphragmatic movement averaged 2.62 mm with a standard deviation of 1.28 mm. The day-to-day variation of diaphragmatic positions was less than 5 mm. The held-breath self-gating technique resulted in a reduction of diaphragmatic movement by an average of 11.9 mm when compared to that seen during tidal breathing. CONCLUSION: In the radiotherapeutic management of non-small-cell lung cancer, this HBSG technique offers a simple method that provides superior immobilization of the diaphragm compared to tidal breathing. Clinical implementation of this technique should allow for a reduction of treatment margins, thus sparing more normal tissues and facilitating dose escalation.

Aged↗
PubMed2001

Long-Term (10-15 years) follow-up after Burch colposuspension for urinary stress incontinence.

The study group comprised 127 patients who underwent a Burch colposuspension for urinary incontinence. All had undergone urodynamic investigation both pre- and postoperatively. All patients had a mean follow-up of 12.4 years (range 10-15); 109 patients had an additional urodynamic investigation at least 10 years after the operation. Following surgery there was an improvement in symptoms of frequency (P<0.001), urgency (P<0.01) and urge incontinence (P<0.001). The cure rate was 93.7%. The only significant changes found on urodynamics were the measurements of the pressure transmission ratio, which were higher postoperatively (P<0.001) and remained so after 10 years. The most frequent postoperative complications were de novo detrusor instability (16.6%) and anatomical defects (18.7%). All failed cases were found during the first postoperative year. De novo detrusor instability appeared in 12/17 patients during the first year of follow-up. Postoperative anatomical defects were found only in 4/24 patients after 5 years. Ten years postoperatively most of the anatomical defects had been detected (20/24), stressing the need for long-term follow-up.

Adult↗
PubMed2001

Immunohistochemical comparison of primary peritoneal and primary ovarian serous papillary carcinoma.

Twenty-six patients, meeting strict criteria for primary peritoneal serous papillary carcinoma (PPSPC), were matched to 22 patients with ovarian serous papillary cancer (OSPC) for age and stage. Immunohistochemistry was used to determine the status of estrogen receptors (ER), progesterone receptors (PR), the expression of cell proliferation marker Ki-67, and the overexpression of HER-2/neu and p53 protein. Of the PPSPCs, 53.8% were poorly differentiated, as were 18.2% of the OSPCs (p = 0.012). Positive immunostaining for ER and PR was less in PPSPCs (30.8% and 46.2%, respectively) than OSPCs (72.7% and 90.9%; p = 0.003 and p = 0.001, respectively). Conversely, a significant increase in the expression of Ki-67 was found in PPSPCs (37.7%) versus OSPCs (26.8%) (p = 0.039). The same trend was found for HER-2/neu, being overexpressed in 38.5% of the PPSPC versus 9.1% of the OSPCs (p = 0.019). Overexpression of p53 was found in 30.8% of the PPSPCs and 45.4% of the OSPCs (not significant). There was a significantly worse survival rate for PPSPCs than for OSPCs (p = 0.017), yet none of the studied parameters were significantly correlated with survival within the PPSPC and OSPC groups. The significantly different immunohistochemical expression of ER, PR, Ki-67, and HER-2 in PPSPCs compared with OSPCs suggests that different molecular events may lead to tumorigenesis in these two cancers.

Cell Division↗
PubMed2001

Reduced reproduction with increased abortion rate in transgenic mice that overexpress 15-lipoxygenase.

15-Lipoxygenase (15-LOX) is a lipid-oxidizing enzyme that is involved in cell cycle regulation. To evaluate the effect of 15-LOX on reproduction, we studied transgenic mice that overexpress 15-LOX. The transgene was introduced over the genetic background of the low density lipoprotein receptor deficient mice (LDL-R(-/-)) and reproduction was compared to LDL-R(-/-) mice. We found a lower pregnancy rate in the 15-LOX/LDL-R(-/-) mice as compared to the LDL-R(-/-) mice (62.74 vs. 79.1%, p < 0.01). Additionally, a remarkably higher number of resorptions per pregnancy was found in the 15-LOX/LDL-R(-/-) mice (16.7 vs. 3.27%, p < 0.001) and it was accompanied by a significantly higher activity of the 15-LOX enzyme in these resorptions as compared to other tissues. These findings may implicate a role for 15-LOX in the development of spontaneous abortions.

Abortion, Spontaneous↗
PubMed2001

Outcome of surgical treatment for superficial dyspareunia from vulvar vestibulitis.

OBJECTIVE: To evaluate the results of surgical treatment for superficial dyspareunia, as manifested by patient satisfaction, as well as epidemiologic characteristics of women with this medical problem. STUDY DESIGN: A questionnaire was sent to 69 women six months after the operation. It included questions about treatment before surgery and the impact of pain on the sexual relationship before and after the operation. Demographic, social and general health data were recorded before the operation. All patients returning the questionnaire were examined. RESULTS: Fifty-four (78%) patients replied. Half of those abstained from sexual relations before surgical treatment. Sixty-seven percent of patients required more than six visits to various physicians, before vestibulitis was diagnosed. Prior to surgery, 80% of patients received conservative treatment, whereas after surgery only 34% required it. A moderate to excellent improvement was reported after surgery by 45 (83%) patients. Repeat surgery (n = 7) resulted in further improvement in four patients. There were no major operative complications. Forty-five patients (83%) were satisfied with the results and would recommend the surgery to other women with this clinical problem. CONCLUSION: Surgical treatment for superficial dyspareunia from vestibulitis is quite safe and results in a high rate of patient satisfaction.

Adult↗
PubMed2001

Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium.

OBJECTIVE: The aim of this study was to determine whether immunohistochemical analysis of molecular parameters can provide an alternative method for classification of endometrial cancer cases according to their aggressiveness. METHODS: Sixty-four cases of endometrial carcinoma were assigned to three groups: group I--28 cases of endometrioid well and moderately differentiated (G1-G2) carcinoma; group II--14 cases of endometrioid poorly differentiated (G3) carcinoma; group III--22 cases of serous papillary endometrial cancer. Immunohistochemistry was used to determine the existence of estrogen receptors (ER), progesterone receptors (PR), and the expression of bcl-2, p53, HER-2/neu and Ki-67. RESULTS: There was a significant difference in the immunohistochemical profile of the studied molecular parameters comparing the three study groups. The endometrioid G1-G2 cases (group I) were characterized by increased immunoreactivity for ER and PR (85.7% and 78.6%, respectively), increased immunoreactivity for bcl-2 (42.8%) and low expression of p53 (14.3%) and HER-2/neu (14.3%). In contrast to group I cases, the serous papillary endometrial cancer cases (group III) were characterized by immunonegativity for ER, PR and bcl-2 and high immunoreactivity for p53 (81.8%) and HER-2/neu (45.4%). The endometrioid G3 cases (group II) demonstrated an intermediate immunoprofile, characterized by immunonegativity for ER, PR and HER-2/neu, low immunoreactivity for bcl-2 (7.1%) and high expression of p53 (57.1%). The expression of Ki-67 did not differ significantly comparing the different cases of endometrial cancer. CONCLUSION: This study provides evidence that the immunohistochemical analysis of endometrial carcinoma differentiates between different grades and histological types, thus being useful in the distinction of high risk cases.

Aged↗