Endometrial fluid biomarkers and their potential as predictors of successful embryo implantation.

Background: Embryo implantation is a complex biological process which requires synchronized dialogue between the receptive endometrium and the blastocyst. The endometrium, however, is only receptive to embryo implantation for a very short period. Recurrent implantation failure (RIF) is a major challenge in assisted reproductive techniques mainly due to impaired receptivity, but there is still a need for a reliable and valid clinical test to assess endometrial receptiveness, especially at embryo transfer time. The aim of this review is to investigate what is currently known about the contribution of endometrial fluid (EF) to endometrial receptivity by identifying its potential biomarkers. Methods: This study involved an extensive search of the electronic databases PubMed and Cochrane, covering the period from 2011 to 2022. A combination of Medical Subject Headings with the terms 'endometrial fluid' and 'embryo implantation' was used. Results: Several different proteins presented in the endometrial cavity fluid have been described but the most consistent as potential biomarkers were Proprotein Convertase 6 (PC6), Vascular Endothelial Growth Factor (VEGF), PIGF (Placental growth factor), ß3 integrin, Colony Stimulating Factor-3 (CSF-3), Leukaemia inhibitory factor (LIF), glycodelin and extracellular vesicles (EVs). Conclusions: Strong indicators support the use of uterine fluid collection as a non-invasive tool for receptivity assessment. Therefore, it could improve outcomes of assisted reproductive techniques.

Increased transglutaminase 2 and GLUT-1 expression in breast tumors not susceptible to chemoprevention with antioxidants.

GOALS: Expression of GLUT-1 and transglutaminase 2 is increased in aggressive breast cancer, whereas claudin-1, which is expressed in normal tissues, is absent in such tumors. This experimental study was undertaken to establish the aggressiveness and prognosis of DMBA-induced mammary tumors in female Wistar rats based on the assessment of these markers. MATERIALS AND METHODS: The rats were divided into two groups, a control group (n = 70) and a chemoprevention group (n = 70). Breast tumors were induced in both groups by administration of 7,12-dimethylbenz[a] anthracene (DMBA). The chemoprevention group also received alpha-tocopherol and a solution of micronutrients containing ascorbic acid and selenium. Neoplastic lesions of both groups were randomly selected for immunohistochemical assessment of the expression of GLUT-1, transglutaminase 2 and claudin-1. RESULTS: A higher proportion of mammary tumors expressed GLUT-1 and transglutaminase 2 in the chemoprevention group. Claudin-1 expression was absent in all tumors of both groups. CONCLUSIONS: These results are suggestive of increased aggressiveness of tumors not susceptible to chemoprevention by the agents used in this study.

Clear cell carcinoma arising from abdominal wall endometriosis - Brief report and review of the literature.

•Endometriosis-associated abdominal wall cancer is a rare entity with poor prognosis.•Personal history of C-section is extremely relevant.•The treatment consists in a wide local excision with adjuvant chemotherapy.•Proper treatment of abdominal endometriosis could prevent these situations.

Molecular detection of EGFRvIII-positive cells in the peripheral blood of breast cancer patients.

The aim of this study is to evaluate epidermal growth factor receptor variant III, EGFRvIII, a cancer specific mutant, as a possible marker for the diagnosis of breast cancer occult systemic disease. EGFRvIII mRNA was identified by an RT-nested PCR with a high sensitivity. In 102 women studied, the mutant was detected in the peripheral blood of 30% of 33 low risk, early stage patients, in 56% of 18 patients selected for neoadjuvant chemotherapy, in 63.6% of 11 patients with disseminated disease and 0% of 40 control women. In low risk, early stage patients, the presence of one or more tumour characteristics predicting recurrence such as the absence of oestrogen receptors and the presence of ERBB2 or histologic grades G2/G3 was significantly associated with EFGRvIII detection (p<0.05). EGFRvIII mRNA has characteristics to be a useful marker for the diagnosis of occult systemic disease in breast cancer. Follow-up studies will evaluate its clinical value as a decision criterion for systemic therapy.

Chemoprevention of DMBA-Induced Mammary Tumors in Rats by a Combined Regimen of Alpha-Tocopherol, Selenium, and Ascorbic Acid.

This experimental study was designed to evaluate the efficacy of associated naturally occuring antioxidants in the prevention of chemically induced breast cancer using DMBA in virgin female Wistar rats. Rats were randomly allocated to three groups: control group (CG; n = 20), induction group (IG; n = 100), and prevention group (PG; n = 70). A single dose (65 mg/kg) of DMBA was administered in the IG and PG animals at 50 days of age. PG animals also received a single dose of alpha-tocopherol (200 mg/rat) 1 hour after DMBA administration and an association of selenium (p-XSC, 40 ppm/day/rat) and ascorbic acid (540 mg/day/rat) in drinking water, daily, from carcinogenic induction until necropsy. Macroscopic study and pathology revealed a significantly lower development of neoplasms in the PG animals (p < 0.05); the number of rats with mammary tumors, breast cancer incidence, and the number of malignant breast tumors per rat as well as per tumor-bearing rat were significantly decreased in the PG animals. Other types of primary neoplasms existing in the IG animals totally disappeared in the PG animals. Immunostaining to hormone steroid receptors (ER and PR) and cathepsin D was similar in both groups. Overexpression of p53 and metallothioneine was significantly increased in the PG animals (p < 0.05) and immunostaining to bromodeoxiuridin and Ki-67 was also stronger in the remaining tumors in the PG animals. These data thus add to the accumulating evidence that those micronutrients in combination seem to be effective in reducing the incidence of malignant tumors. Nevertheless, remaining tumors seem to present more aggressive behavior and characteristics of drug resistance.

[Atypical glandular cells of undetermined significance (agus) which entity?]. / Atipias glandulares de significado indeterminado (agus) que entidade?

OBJECTIVE: The aim of this study was to determine the incidence and evolution of the atypical glandular cells of undetermined significance (AGUS) without associated lesions identified on cervical Pap smear. MATERIAL AND METHODS: Retrospective study concerning 33.923 cervicovaginal smears performed in the Cytopathology Department of the Coimbra University Hospital (H.U.C.) between January 1995 an December 1997. AGUS diagnosis, isolated or associated with other lesions, was made in 716 cases. Four hundred fourty-four of them were refered to patiens of the H.U.C. Ginecology Department. One hundred seventy-seven cases were classified as AGUS alone; 62 related to the Ginecology Department where follow-up was performed within a period from 3 to 36 months. This study concerns exclusively AGUS patients without associated lesions (N=62). RESULTS: Sixty two cases of isolated AGUS were studied; the incidence was 0,52% and the average age 44,7 ±11,7 [19-75] years old. Follow-up, performed between 3 and 36 months, revealed: isolated cervical smears (N=9), cervical smears and endocervical curettage (N=15), cervical smears with colposcopy and directed biopsy and/or endocervical curettage (N=11), cervical smears and colposcopy (N=19). Total histerectomy was performed in 8 cases by other reasons. Cervical smears were normal in 91,2 % of the cases (N=62). Histologic examination of surgical samples refering to total histerectomy, cervix biopsies was normal in 14 cases (38,9%), revealed cronic cervicitis in 14 cases, LSIL in 7 cases and endocervical polyps in one case. CONCLUSION: In spite of the reduced data of the study, the results point to no need to an agressive therapeutical approach at AGUS diagnosis in Pap smears.