PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors.

PURPOSE: Clonal loss of PTEN expression occurs frequently in endometrial carcinoma and endometrial hyperplasia. Limited data from immunohistochemical studies suggest that PTEN-null appearing endometrial glands are detectable in women without pathologic abnormalities, but the relationship of PTEN expression to endometrial cancer risk factors has not been extensively explored. We evaluated relationships between endometrial cancer risk factors and loss of PTEN expression in a set of benign endometrial samples prospectively collected from women undergoing hysterectomy and in endometrial cancer tissues from a population-based case-control study. METHODS: We used a validated PTEN immunohistochemical assay to assess expression in epidemiological studies designed to assess benign endometrium [Benign Reproductive Tissue Evaluation Study (n = 73); Einstein Endometrium Study (n = 19)], and endometrial cancer [Polish Endometrial Cancer Study (n = 148)] tissues. Associations between endometrial cancer risk factors (collected via study-specific risk factor questionnaires) and PTEN expression in endometrial tissues were determined using Fisher's exact tests. RESULTS: PTEN loss was detected in 19% of benign endometrial tissues versus 55% in endometrial cancers. NSAID use was statistically significantly associated with PTEN loss in the benign endometrium (p = 0.02). CONCLUSION: Our data demonstrate that PTEN loss is detectable in endometrial tissues that are benign and malignant, with substantially more frequent loss in endometrial cancer compared with benign endometrium. However, alterations in expression were unrelated to most risk factors in this analysis, except for the association with NSAID use, which may represent a chance finding or reverse causality among patients with endometriosis who may have PTEN pathway abnormalities in eutopic endometrium. Further evaluation of factors associated with PTEN loss and long-term follow-up of women with PTEN-null endometrial glands may be useful in understanding early events in endometrial carcinogenesis.

Brush cytology of the fallopian tube and implications in ovarian cancer screening.

STUDY OBJECTIVE: To determine whether fallopian tube epithelial cells adequate for cytopathology can be obtained via a minimally invasive approach using brush cytology. DESIGN: Prospective feasibility study (Canadian Task Force classification II-1). SETTING: Tertiary-care university-based teaching hospital. PATIENTS: Ten patients who underwent laparoscopic hysterectomy, with or without adnexal surgery, because of benign indications. INTERVENTIONS: Attempted hysteroscopic and laparoscopic brush cytologic sampling of the fallopian tubes. MEASUREMENTS AND MAIN RESULTS: ThinPrep slides and cell blocks were prepared and analyzed. P53 and KI-67 immunostaining was performed on cell block specimens if adequate cellularity was present. The first 5 patients underwent attempted hysteroscopic sampling of the fallopian tube, with successful collection only in 1 patient. The protocol was then modified to enable sampling of the fallopian tube laparoscopically as well as hysteroscopically. In the other 5 patients sampling of the fallopian tubes was successful laparoscopically, including successful sampling hysteroscopically in 1 patient. The brush biopsy catheter could not be passed through the entire length of the fallopian tube in either the hysteroscopic or laparoscopic approach. All cytologic findings were interpreted as benign, although findings of nuclear overlapping, crowding, and small nucleoli were initially considered benign atypia. Immunohistochemistry for P53 and KI-67 yielded uniformly negative findings. CONCLUSION: To our knowledge, this is the first study to describe endoscopic brush cytology of the fallopian tubes with correlated cytologic narrative. In the future, cytologic sampling of the fallopian tube may have implications for an ovarian cancer screening test.

Discovery and validation of methylation markers for endometrial cancer.

The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies. We compared DNA methylation values of 1,500 probes representing 807 genes in 148 population-based endometrial carcinoma samples and 23 benign endometrial tissues. Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform. Further replication was conducted in The Cancer Genome Atlas and in prospectively collected endometrial brushings from women with and without endometrial carcinomas. We identified 114 CpG sites showing methylation differences with p values of ≤ 10(-7) between endometrial carcinoma and normal endometrium. Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY and SOX1) were selected for further replication. Age-adjusted odds ratios for endometrial cancer ranged from 3.44 (95%-CI: 1.33-8.91) for ASCL2 to 18.61 (95%-CI: 5.50-62.97) for HTR1B. An area under the curve (AUC) of 0.93 was achieved for discriminating carcinoma from benign endometrium. Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the candidate markers. This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy.

Mechanical bowel preparation for gynecologic laparoscopy: a prospective randomized trial of oral sodium phosphate solution vs single sodium phosphate enema.

STUDY OBJECTIVE: To compare the effect of mechanical bowel preparation using oral sodium phosphate (NaP) solution vs single NaP enema on the quality of the surgical field in patients undergoing advanced gynecologic laparoscopic procedures. DESIGN: Single-blind randomized controlled trial (Canadian Task Force classification I). SETTING: Academic teaching hospital. PATIENTS: Women undergoing gynecologic laparoscopic surgery. INTERVENTIONS: Administration of either oral NaP solution or single NaP enema for preoperative bowel preparation. MEASUREMENTS AND MAIN RESULTS: One hundred fifty-six women were enrolled, and 145 were randomized to receive either oral NaP solution (n = 72) or NaP enema (n = 73). Sixty-eight women in the oral solution group and 65 in the enema group completed the study. Assessment of the quality of the surgical field and bowel characteristics was performed using a surgeon questionnaire using Likert and visual analog scales. No significant differences were observed between the 2 groups in evaluation of the surgical field, bowel handling, degree of bowel preparation, or surgical difficulty. Surgical field quality was graded as excellent or good in 85% of women in the oral solution group and 91% of women in the enema group (p = .43). When surgeons were asked to guess the type of preparation used, they were correct only 52% of the time (κ = 0.04). Assessment of patient quality of life in the preoperative period was performed using a self-administered questionnaire using a visual analog scale. Severity of abdominal bloating and swelling, weakness, thirst, dizziness, nausea, fecal incontinence, and overall discomfort were significantly greater in the oral solution group. Women in the oral solution group also rated the preparation as significantly more difficult to administer, and were significantly less willing to try the same preparation in the future. CONCLUSION: Quality of the surgical field in patients undergoing advanced gynecologic laparoscopic procedures is similar after mechanical bowel preparation using either oral NaP solution and NaP enema. Adverse effects are more severe with oral NaP solution compared with NaP enema administration.