Uterine Biopsies Research Articles

Development and Application of Human Virtual Excitable Tissues and Organs: From Premature Birth to Sudden Cardiac Death

The electrical activity of cardiac and uterine tissues has been reconstructed by detailed computer models in the form of virtual tissues. Virtual tissues are biophysically and anatomically detailed, and represent quantitatively predictive models of the physiological and pathophysiological behaviours of tissue within an isolated organ. The cell excitation properties are quantitatively reproduced by equations that describe the kinetics of a few dozen proteins. These equations are derived from experimental measurements of membrane potentials, ionic currents, fluxes, and concentrations. Some of the measurements were taken from human cells and human ion channel proteins expressed in non-human cells, but they were mostly taken from cells of other animal species. Data on tissue geometry and architecture are obtained from the diffusion tensor magnetic resonance imaging of ex vivo or post mortem tissue, and are used to compute the spread of current in the tissue. Cardiac virtual tissues are well established and reproduce normal and pathological patterns of cardiac excitation within the atria or ventricles of the human heart. They have been applied to increase the understanding of normal cardiac electrophysiology, to evaluate the candidate mechanisms for re-entrant arrhythmias that lead to sudden cardiac death, and to predict the tissue level effects of mutant or pharmacologically-modified ion channels. The human full-term virtual uterus is still in development. This virtual tissue reproduces the in vitro behaviour of uterine tissue biopsies, and provides possible mechanisms for premature labour.

Effect of a povidone-iodine intrauterine infusion on progesterone levels and endometrial steroid receptor expression in mares

BackgroundIntrauterine infusions have been widely used for the treatment of endometritis in the mare. Nevertheless, their consequences on endocrine and endometrial molecular aspects are unknown. We studied the effect of a 1% povidone-iodine solution intrauterine infusion on progesterone levels, endometrial histology and estrogen (ERα) and progesterone (PR) receptor distribution by immunohistochemistry.MethodsFourteen healthy mares were used in this study. Estruses were synchronized and seven mares were treated with intrauterine infusions at days 0 and 2 post ovulation of two consecutive estrous cycles. Uterine biopsy samples were taken on days 6 and 15 post ovulation.ResultsThe treatment did not induce an inflammatory response indicating endometritis, neither affected the ERα. However, it reduced the percentage of PR positive cells (PPC) on day 6 (deep glandular epithelium, control: 95.7 vs. infused: 61.5, P < 0.05). Treated mares tended to have lower progesterone levels on day 2 (3.9 ng/ml vs. 6.6 ng/ml, P = 0.07), and higher levels on day 15 compared with controls (4.4 ng/ml vs. 1.3 ng/ml, P = 0.07).Conclusiona 1% povidone-iodine infusion during days 0 and 2 post ovulation in healthy mares did not induce histological changes indicating endometritis, but altered progesterone concentrations and reduced the expression of endometrial PR at day 6 without affecting the ERα. These changes could reduce embryo survival.

Choriocarcinoma in a 73-year-old woman: a case report and review of the literature

IntroductionChoriocarcinoma is a highly malignant tumor of trophoblastic origin. Most cases present within one year of the antecedent pregnancy (molar or non-molar). However, very rarely, choriocarcinoma can develop from germ cells or from dedifferentiation of endometrial carcinoma into choriocarcinoma. This article concerns a case of choriocarcinoma developing 38 years after the patient's last pregnancy and 23 years after menopause.Case presentationA 73-year-old African-American woman presented with a three-week history of vaginal bleeding. A vaginal mass was seen on pelvic examination. Ultrasonography showed a thickened complex endometrial echo. Her β-human chorionic gonadotrophin level was found to be elevated (2,704,040 mIU/mL). Vaginal and uterine biopsies were suggestive of choriocarcinoma. Immunohistochemistry tests were positive for β-human chorionic gonadotrophin as well as cytokeratin and negative for octamer binding transcription factor 3/4 and α-fetoprotein, supporting the diagnosis of choriocarcinoma. A combination of etoposide, methotrexate, and dactinomycin, followed by cyclophosphamide and vincristine (the so-called EMA/CO regimen) was initiated. After seven cycles of chemotherapy, her β-human chorionic gonadotrophin level dropped below 5 mIU/mL. Our patient is being followed up at our oncology institute.ConclusionsWe report an extremely rare case of choriocarcinoma arising 23 years after menopause. A postmenopausal woman presenting with vaginal bleed from a mass and β-human chorionic gonadotrophin elevation should be evaluated by immunohistochemical analysis to rule out the possibilities of a germ cell origin of the tumor or dedifferentiation of an epithelial tumor. Absence of octamer binding transcription factor 3/4, α-fetoprotein and CD-30 staining helps in exclusion of most germ cell tumors. DNA polymorphism studies can be used to differentiate between gestational and non-gestational tumor origin. These require fresh tissue samples and are time consuming. Finally, the effective first-line therapy for β-human chorionic gonadotrophin-producing high-risk gestational as well as non-gestational trophoblastic tumors is combination chemotherapy (the EMA/CO regimen). Therefore, treatment should be commenced when a potential diagnosis of metastatic trophoblastic tumor is being considered.

Postpartum toll-like receptors and β-defensin 5 mRNA levels in the endometrium of Holstein cows

Toll-like receptors (TLRs) and β-defensins are important components of the innate immune system. This study aimed to evaluate endometrial mRNA levels of TLRs (1/6, 2, 4, and 5) and β-defensin 5 in Holstein cows by quantitative real time RT-PCR. Uterine biopsies were performed from 6 to 12 h after parturition, and cows were divided into two groups: (i) cows with placental retention and clinical signs of uterine infection until 45 days postpartum ( n = 10) or (ii) cows with normal puerperium ( n = 10). All cows had detectable levels of TLRs and β-defensin 5 mRNAs, but these levels did not differ between groups ( P > 0.05). Levels of TLR4 mRNA had a positive and significant correlation with the time required for uterine involution in both groups.

Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives in pregnant human myometrium

The aim of this study was to assess the involvement of lipoxygenase (LOX) metabolic pathways in uterine tissues from pregnant women as well as the combined inhibition of LOX and cyclooxygenase (COX) on contractile activity. Uterine biopsies were performed from consenting women undergoing elective caesarean sections at term (n = 24). Western blot analysis and isometric tension measurements were performed in vitro on fresh human myometrial strips. Concentration-response curves to arachidonic acid (AA) 861 and baicalein (5- and 12-LOX inhibitors, respectively) were performed. The combined effects of baicalein and indomethacin were also assessed. Contractile activities were quantified by calculating both amplitude and the area under the curve over 20 minute periods. 5- and 12-LOX were present in all tested tissues. Addition of AA861 or baicalein resulted in tocolytic effects (P < .05). Finally, the combined inhibition of both COX and 12-LOX pathways resulted in additive tocolytic effects. 5- and 12-LOX pathways modulate human myometrium contractility.

Bacteriological and cytological findings during the late puerperal period after two different treatments of retained placenta followed by acute puerperal metritis

The aim of the study was to compare the effect of two acute puerperal metritis (APM) treatment protocols on uterine condition during the late puerperal period (5th to 7th week). Late gestation healthy cows (n = 21) were divided randomly in three equal groups. Parturitions were induced. Treatments of APM were started on the third day postpartum (PP). Group A was treated with an oxytocin analogue carbetocin for three days and intrauterine administration of cephapirin between days 15 and 17. Group B was given intramuscular injection of ceftiofur for five days followed by two injections of prostaglandin F2α, at an interval of 12 h, on the eighth day PP. Group C served as the control group with no treatment. Body temperature was recorded daily for 14 days PP. Uterine biopsies for bacteriology, and uterobrush samples for cytology, were taken once a week from the 5th to 7th week postpartum. No differences were found in body temperature on day 14 PP, presence of bacteriological infections and disappearance of uterine inflammatory signs diagnosed by cytological examination between experimental groups.

Genistein aglycone: A new therapeutic approach to reduce endometrial hyperplasia

Endometrial hyperplasia without cytological atypia is commonly treated with progestins, but other treatment regimes may be available with equivalent efficacy and low side effects. A randomized double-blind, placebo and progesterone-controlled clinical trial to evaluate the effects of genistein aglycone in reducing endometrial hyperplasia. A group of 56 premenopausal women with non-atypical endometrial hyperplasia were enrolled and received: genistein aglycone (n=19; 54 mg/day); norethisterone acetate (n=19; 10 mg/day on days 16-25 of the menstrual cycle) or placebo (n=18) for 6 months. Hysteroscopy was performed with biopsies and symptomology assessed at baseline, 3 and 6 months of administration. The effect on estrogen (ER) and progesterone receptors (PR) expression in uterine biopsies were assessed after 3 and 6 months. For each treatment follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), sex hormone-binding globulin (SHBG) and progesterone (PG) levels were also evaluated. After 6 months, 42% of genistein aglycone-administered subjects had a significant improvement of symptoms (histologically confirmed in the 29%) compared to 47% of norethisterone acetate subjects (histologically confirmed in the 31%), but only 12% in the placebo group with 19% exhibiting worsening symptoms and increased endometrial thickness. No significant differences were noted for hormone levels for any treatment, but immunohistochemical analysis revealed significantly reduced staining for ER-alpha and PR and enhanced ER-beta1 staining in genistein-administered subjects associated with a complete regression of bleeding. These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women that cannot be treated with progestin.

Large cell neuroendocrine carcinoma with sarcomatous changes of the endometrium: A case report with immunohistochemical studies and molecular genetic study of KIT and PDGFRA

The author herein reports a very rare case of large cell neuroendocrine carcinoma (LCNEC) with sarcomatous changes of the endometrium. A 40-year-old woman was admitted to our hospital because of abnormal uterine bleeding. Gynecologic examination and imaging modalities revealed a polypoid tumor of the uterine corpus. Uterine curettage biopsy revealed a sarcomatous undifferentiated carcinoma. Simple hysterectomy, salpingo-oophorectomy, extensive lymph node dissection, and omentectomy were performed. The patient was diagnosed as having FIGO stage Ib (T1N0M0) carcinoma, and adjuvant chemotherapy was performed. The patient is now alive 16 months after the operation. Pathologically, a polypoid tumor measuring 3×2×2 cm 3 was found in the uterine corpus. Histologically, the tumor consisted of relatively large-sized carcinoma cells without differentiation. The tumor cells have abundant cytoplasm and prominent nucleoli. It was composed of a spindle cell component (40%) and an epithelioid component (60%). A gradual transition between the two was recognized. Immunohistochemically, both elements showed the same immunophenotypes. The carcinoma cells were positive for cytokeratin, vimentin, CA125, CD34, estrogen receptor, progesterone receptor, p53 protein, Ki-67 antigen (80%), synaptophysin, CD56, KIT, and PDGFRA. They were negative for epithelial membrane antigen, CEA, desmin, S100 protein, melanosome, α-smooth muscle actin, chromogranin, and neuron-specific enolase. A molecular genetic analysis revealed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The final diagnosis was LCNEC with sarcomatous changes.

Effect of vascular endothelial growth factor and interleukin-1β on apoptosis in endometrial cell cultures from patients with endometriosis and controls

The aim of this study was to evaluate the effect of vascular endothelial growth factor (VEGF) and interleukin-1beta (IL-1beta) on apoptosis induced by leuprolide acetate (LA) in endometrial epithelial cell cultures from patients with endometriosis. Primary endometrial epithelial cell cultures were obtained from uterine endometrial biopsies of patients with endometriosis and control women. Endometrial epithelial cells were incubated with LA; a combination of LA and VEGF; a combination of LA and IL-1beta; or in basal conditions. LA was added 3h prior to addition of VEGF and IL-1beta. After stimulation, the percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique and Bax expression was assessed by western blot. Treatment with LA enhanced the percentage of apoptotic cells in endometrial epithelial cells from subjects with endometriosis and control subjects. Addition of either VEGF or IL-1beta after exposure to LA restored the percentage of apoptotic cells to basal levels. Moreover, treatment with LA increased Bax expression in endometrial epithelial cells from patients with endometriosis. This effect was reverted by the addition of either VEGF or IL-1beta. Our results show that VEGF and IL-1beta reduce apoptosis and decrease Bax expression in endometrial epithelial cells from patients with endometriosis. This study suggests that VEGF and IL-1beta may protect endometriotic cells from undergoing apoptosis in addition to exerting their pro-angiogenic role.

咽頭痛を初発症状としたメトトレキサート（ＭＴＸ）関連リンパ増殖性疾患例

We report a case of unusually long rheumatoid arthritis (RA) with methotrexate (MTX) and related factors. A 60-year-old woman with a 35-year RA history and 2 weeks of sore throat. For 19 years before presentation, she had been administrated oral MTX weekly at 7.5 mg. Laryngofiberscopy showed a tumor on the oropharynx, at the left tongue root. Enhanced computed tomography (CT) showed neck swelling and axillary, lateroabdominal subcutaneous, and inguinal lymph nodes, nodular thyroid lesion, lung, and liver. Gastroscopy showed a gastric tumor and uteroscopy a uterine tumor. Fine needle aspiration from a neck lymph node and thyroid showed malignant lymphoma and oropharyngeal, gastric, and uterine biopsy showed diffuse large B cell lymphoma. She was diagnosed elsewhere with MTX-associated lymphoproliferative disorders (MTX-LPD), and MTX was discontinued. Neck lymph node and oropharyngeal tumor shrank 2 weeks after MTX withdrawal, and CT 4 months later showed all lesions had disappeared. One year after MTX withdrawal, the woman had no evidence of recurrence.

Collagen histomorphometric evaluation in uterin tissue samples before and after treatment of uterine fibroids with arterial embolization

To analyze histomorphometric consequences of the uterine arteries embolization (UAE) in the uterine tissue, especially by collagen tissue quantification through uterine biopsy, before and after treatment of uterine leiomyoma. 15 patients with symptomatic leyomioma and/or infertility, submitted to UAE, participated in the study according to the study exclusion criteria, after having signed an informed consent. Uterine biopsy was performed in the secretory phase of the menstrual cycle, before and three months after the procedure, to evaluate the collagen. After the histological processing of the material, 3 micro slices were prepared, some of them dyed with hematoxiline-eosin (HE) and others with the specific dye for collagen fibers (Picrosirius red). Then, the slides were examined and interpreted, and the collagen quantified. The amount was calculated as the percent of the area composed by collagen, and the result expressed in mean+/-standard deviation (SD). Data has then been submitted to statistical analysis by Student's paired t test (p<0.05). The presence of smooth muscle cells was observed in the biopsies performed before the treatment, surrounded by a rich network of collagen fibers, which are part of the tumor, blood vessels and fibroblast nuclei. On the slides of biopsies performed after the treatment, it was observed the presence of widespread coagulation necrosis, vascular thrombosis, calcification and lymphoplasmocitary infiltration areas and clear reduction of the collagen component. The percentage of collagen fibers was higher in the pre-UAE group (84.07+/-1.41), than in the post-UAE (81.05+/-1.50) group, with p<0.0001, and 95% confidence interval (CI95%) from 2.080 to 3.827. The quantitative and qualitative collagen reduction clearly shows that the proposed treatment is efficient in reducing the tumoral mass, composed mainly by collagen fibers intermingled with neoplasic smooth muscle cells. Nevertheless, complementary studies are needed to investigate the functional and biological consequences of these histological changes.

Early regulators in abortion and implications for a preeclampsia model

This paper reports a summary of our comparative analysis of the uterine expression of interleukin-23 (IL-23), IL-27 and TWEAK in the CBA/J femalexDBA/2 male mouse mating combination, a model of immune-mediated early pregnancy loss. Compared with the MHC-identical CBA/JxBALB/c mating combination, which yields successful pregnancies, immunohistochemistry and qPCR in uterine tissue showed an immediate post-mating IL-27 hyper-expression after mating with DBA/2 males. Intra-uterine TWEAK expression was present in females mated with DBA/2 or Balb/c males from days 0.5 to 4.5 post-coitum (pc), peaking on day 0.5 pc together with uterine TNFalpha. In uteri of DBA/2 mated mice, TWEAK declined to almost undetectable levels on days 6.5-9.5 pc, a steeper drop than in BALB/c mated mice where TWEAK remained detectable. In both mating combinations, neutralisation of TWEAK by antibodies increased resorption rates, but surprisingly, so did IL-27 neutralisation. The complement regulator mannan binding lectin-A (MBL-A), but not MBL-C, was present on day 4.5 pc especially after mating with DBA/2 males. High levels of MBL are present in the uterine luminal fluid of sterile women, and possible functions for TWEAK and MBL in human implantation are indicated by their protein and mRNA expression in uterine biopsies from infertile and fertile individuals. Consistent with the results in mice, increased MBL expression is linked with pregnancy failure. Serum and uterine VEGF and VEGF receptor levels are also different between fertile and sterile patients. The implications of these findings for utilising the CBA/JxDBA/2 mating combination as an early onset model of preeclampsia are discussed.

Why eicosanoids could represent a new class of tocolytics on uterine activity in pregnant women

The purpose of this study was to assess the effects of exogenous eicosanoids on spontaneous uterine contractile activity. Eight uterine biopsies were performed from women who were undergoing elective cesarean delivery. Tension measurements were performed in vitro on myometrial strips. Contractile activities were quantified by the calculation of the area under the curve. The effects of eicosanoids and specific enzyme inhibitors were assessed. Fractions from various uterine tissues were analyzed by Western blot. Data demonstrate the presence, in some tested tissues, of cytochrome P-450 epoxygenase and soluble epoxide hydrolase, which respectively produce and degrade epoxyeicosatrienoic acid regioisomers. Inhibition of soluble epoxide hydrolase with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid or omega-hydroxylase with N-methylsulfonyl-12,12-dibromododec-11-enamide resulted in a tocolytic effect; N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide, which is an epoxygenase inhibitor, had no effect. Exogenous epoxyeicosatrienoic acids displayed significant tocolytic effects on spontaneous contractile activities. Epoxy- and hydroxyeicosanoids represent new bioactive, arachidonic acid by-products with in vitro tocolytic activities. These findings suggest that cytochrome P-450 isozymes may represent relevant pharmacologic targets under physiopathologic conditions.

Effect of oxytocin and flunixin meglumine on uterine response to insemination in mares

The most probable reason for persistent postbreeding endometritis in mares is weak myometrial contractility. The influence of oxytocin (OT; an ecbolic agent) and flunixin meglumine (FLU; a prostaglandin inhibitor serving as a model for mares with decreased uterine contractility) on uterine response to artificial insemination (AI) was studied in mares with no history of reproductive failure. The mares were treated intravenously with 10 mL saline (Group C, n = 10) or 0.01 IU/kg OT (Group OT, n = 10) 2, 4, 8, and 25 h after AI. Group FLU (n = 11) was treated with 1.1 mg/kg FLU 2 h after AI and with saline thereafter. The mares received the same treatments in the first and third cycles but were sampled either at 8 or 25 h. The amount of intrauterine fluid (IUF) and edema and the number of uterine contractions were recorded before AI and 10 min after the treatments using transrectal ultrasonography. At 8 h after AI, the mares were treated with human chorionic gonadotropin, and, after 8-h or 25-h scans, a 500-mL uterine lavage and a biopsy were performed. Ovulation was confirmed at 48 h and pregnancy 14 to 17 d after AI. No manipulations were done during the second estrus. At 8 h after AI, Group FLU had more polymorphonuclear leukocytes (PMNs) in the uterine lavage fluid than did Group OT (P < 0.05), but uterine contractions did not differ significantly. At 25 h, the PMN concentrations were low in all groups. Group OT rarely showed IUF. The uterine biopsy specimens of Group FLU showed less inflammation of the stroma but more PMNs in the uterine lumen 8 h after AI than that of the control group (P < 0.05). The pregnancy rates did not differ between the groups (63% C, 53% OT, and 50% FLU). Oxytocin rapidly and effectively removed IUF and PMNs after AI and thereby shortened the duration of postbreeding inflammation.

Clinical and Subclinical Endometritis in the Mare: Both Threats to Fertility

Endometritis, a major cause of mare infertility arising from failure to remove bacteria, spermatozoa and inflammatory exudate post-breeding, is often undiagnosed. Defects in genital anatomy, myometrial contractions, lymphatic drainage, mucociliary clearance, cervical function, plus vascular degeneration and inflamm-ageing underlie susceptibility to endometritis. Diagnosis is made through detecting uterine fluid, vaginitis, vaginal discharge, short inter-oestrous intervals, inflammatory uterine cytology and positive uterine culture. However, these signs may be absent in subclinical cases. Hypersecretion of an irritating, watery, neutrophilic exudate underlies classic, easy-to-detect streptococcal endometritis. In contrast, biofilm production, tenacious exudate and focal infection may characterize subclinical endometritis, commonly caused by Gram-negative organisms, fungi and staphylococci. Signs of subclinical endometritis include excessive oedema post-mating and a white line between endometrial folds on ultrasound. In addition, cultures of uterine biopsy tissue or of small volume uterine lavage are twice as sensitive as guarded swabs in detecting Gram-negative organisms, while uterine cytology is twice as sensitive as culture in detecting endometritis. Uterine biopsy may detect deep inflammatory and degenerative changes, such as disruption of the elastic fibres of uterine vessels (elastosis), while endoscopy reveals focal lesions invisible on ultrasound. Mares with subclinical endometritis require careful monitoring by ultrasound post-breeding. Treatments that may be added to traditional therapies, such as post-breeding uterine lavage, oxytocin and intrauterine antibiotics, include lavage 1-h before mating, carbetocin, cloprostenol, cervical dilators, systemic antibiotics, intrauterine chelators (EDTA-Tris), mucolytics (DMSO, kerosene, N-acetylcysteine), corticosteroids (prednisolone, dexamethasone) and immunomodulators (cell wall extracts of Mycobacterium phlei and Propionibacterium acnes).

Local expression of interferon-alpha and interferon receptors in cervical intraepithelial neoplasia.

The present study evaluated mRNA expression of interferon-alpha (IFN-alpha), IFN-alpha receptor subunits (IFNAR-1 and IFNAR-2) and an IFN-stimulated gene encoding the enzyme 2',5'-oligoadenylate synthetase (2'5'OAS) in biopsies on patients with varying grades of cervical intraepithelial neoplasia (CIN I, II and III). Uterine cervix biopsies were collected from women with CIN I, II and III (n = 28) and controls without CIN lesions or human papilloma virus (HPV) infection (n = 17). The presence of high and low-risk HPV DNA was determined using hybrid capture. The mRNA levels of IFNAR-1, IFNAR-2, IFN-alpha and 2'5'OAS were determined by RT-PCR with specific primers. The control group exhibited a greater frequency of IFNAR-1 expression (10/17; 58.3%) than the CIN samples (4/28; 14.2%) (P = 0.0018), while, the expression of IFNAR-2 was also greater in the control samples (11/17; 64.7%) than in the patients with lesions (2/28; 7.1%) (P = 0.0018). Importantly, simultaneous expression of both receptors was observed only in the control group (8/17; 47.0%) (P = 0.0001). Among the CIN samples, there was one case of low expression of mRNA of IFNAR-1 and IFNAR-2. IFN-alpha was present in 14.2% (4/28) of the CIN samples but was not expressed in the control group. mRNA 2'5'OAS were expressed in 28.5% (8/28) of the CIN samples and 11.7% (2/17) of the control samples (not statistically significant). Fifty percent (14/28) of the CIN samples were positive for HPV DNA. Cervical biopsy samples from control women or those without neoplasia or HPV infection displayed higher IFN-alpha receptor expression than those with CIN, while simultaneous expression of both IFN-alpha receptor subunits was found only in the control group. There was no significant difference in mRNA expression of IFN-alpha and 2'5'OAS between the control and CIN groups. Then we concluded that the samples obtained from patients with CIN present low levels of the IFN-alpha receptor mRNA.

The Use of Molecular Markers (p16, Ki-67 and E-Cadherin) in Uterine Cervical Biopsies

Introduction: Cervical cancer is related to the Human Papillomavirus (HPV). The E7 viral DNA sequence in- duces the start of DNA synthesis of infected cell, releasing protein p16. The sequence E6 inhibits apoptosis, with pro- longed survival of cells heavily damaged and changed, with inhibition of p53 protein and increasing of protein Ki-67. In those injured cells, the molecules are reduced to join the cell membrane, the type E-cadherin. Aim: To study the expression of p16 protein in: normal epithelium cervical, cervical lesions, pre-invasive (CIN) persistent and no persistent lesions and invasive carcinoma of the cervix and to correlate with the expression of Ki-67 and E- cadherin. Patients and Methods: 54 uterine cervix biopsies were selected and submitted to immunohistochemical study, with bio- markers p16, Ki-67 and E-cadherin. Results: 1 CIN I (27.9%) and CIN II (47.9%) had lower expression of p16 than in CIN III (73.5%) and invasive carcinoma (72.7%) (p < 0.0005). For Ki-67, invasive carcinoma (57.8%), had a higher expression when compared to CIN I (35.6%), CIN II (51.9%) and CIN III (40.9%) (p = 0.005). E-cadherin expression in invasive carcinoma (46.2%) was lower than in CIN III (56.0%), CIN II (77.4%) and CIN I (82.2%) (p < 0.0005) and, normal epithelium had the greatest E-cadherin ex- pression (89.1%). In persistent and no persistent CIN there was no difference in the expression of the biomarkers, with p16 presenting p = 0.50, Ki-67, p = 0.91 and the E-cadherin a p = 0.43 value. Conclusions: The use of p16, Ki-67 and E-cadherin biomarkers in cervical biopsies with difficult diagnosis could help in the early diagnosis of malignant lesions and support adequate treatment, 2. There is no association between the diagnosis of the biopsy and the persistence of the cervical lesion and, 3. The used biomarkes don't differentiate between persistent CIN and no persistent lesions.

Advanced Alveolar Rhabdomyosarcoma of the Uterus: A Case Report

Alveolar rhabdomyosarcoma is an uncommon malignant soft tissue tumour rarely found in the female genital tract and carries a very poor prognosis especially in adults. A 44 year old premenopausal woman was evaluated for a lower abdominal mass, intermittent unprovoked vaginal bleeding and weight loss. Examination showed a huge abdomino-pelvic mass, and an irregular cauliflower mass protruding from the cervix, from which a biopsy was taken. Exploratory laparotomy revealed a widespread disseminated uterine tumour with an "omental cake" and involving virtually all the abdominal viscera. Debulking surgery was found to be non-beneficial and uterine and omental biopsies were taken. The cervical, uterine and omental biopsies were all diagnosed alveolar rhabdomyosarcoma. Neither chemotherapy nor radiotherapy could be started before the client died of fulminant neoplastic dissemination 17 days postoperatively. While the optimal management of this rare tumour is unknown, early recognition and diagnosis, and a prompt multimodality treatment approach of surgery, chemotherapy and radiotherapy offers the best chance of cure.

Histopathological and molecular evaluation of Holstein-Friesian cows postpartum: Toward an improved understanding of uterine innate immunity

Bovine uterine disease reduces milk yield, impairs fertility and has implications for animal welfare. During involution, the uterus is usually exposed to multiple potential bacterial pathogens which are cleared by successful orchestration of the local inflammatory response. Unsuccessful resolution leads to the development of disease. The aim of this study was to characterize the local innate immune response in the uterus during physiological involution using histopathological and molecular analyses in 9 cows, 2 weeks after calving (early postpartum, EPP), and 4 cows, 9 weeks after calving (late postpartum, LPP). Uterine biopsies taken from each cow were classified by histopathology, and RNA was extracted for molecular analysis. Two EPP cows were classified with a mild, 5 with a moderate and 2 with a severe inflammatory response. Relative gene expression analysis was then performed using quantitative real-time PCR (qRT-PCR) and specific primers for genes encoding Toll-like receptors (TLRs), chemokines, cytokines, acute phase proteins (APPs) and antimicrobial peptides (AMPs). TLR4, transcription factor NFKB1 and the inflammatory cytokines IFNG, IL1A, IL6, IL8, IL12A were all significantly increased in EPP cows ( P < 0.05). Increase in HP, SAA3, TAP and DEFB5 genes was particularly marked in cows with severe inflammation. These results reveal evidence of an inflammatory uterine environment in the early postpartum period with significant induction of both AMP and APP genes. Histopathological grades in EPP cows are underpinned by quantitative changes in gene expression. Understanding the molecular mechanisms contributing to uterine immunity in the early postpartum period may identify candidate genes associated with the resolution of inflammation.

Human papillomavirus infection is principally found with cervical intra-epithelial neoplasia-III in Toluca, State of Mexico

To describe the prevalence of human papillomavirus infection (HPV) in cases of cervical intra-epithelial neoplasia (CIN), micro-invasive carcinoma and invasive carcinoma in Toluca, State of Mexico. Cross-sectional study analysing slides with the diagnosis of CIN I to invasive carcinoma for one year and reporting the presence of HPV; also identifying these cervical-uterine cancer stages noted during one semester in the registery of histopathological studies, at the Department of Pathology, General Regional Hospital 220, Instituto Mexicano del Seguro Social (IMSS). In one year, from a total of 5755 studies, 731 (13%) were of cervical-uterine cancer, 112 (16%) of these were positive for some stage of cervical cancer and 46.43% had HPV infection. In one semester, 2918 histopathological studies were done, 341 (11.68%) of these were cervix uterine biopsies, colposcopies and hysterectomies. 62 women (18.18%) diagnosed with CIN II-III, carcinoma in situ (CIS), micro-invasive carcinoma or invasive carcinoma and finding HPV infection in 51.92% of total cases. The prevalence of HPV was higher than that reported in developed world and CIN II-III are the most common stages in Toluca, State of Mexico.