Profiling the immune landscape in mucinous ovarian carcinoma.

OBJECTIVE: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION: In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.

Clear cell carcinoma of the endometrium.

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

Effects of non-surgical periodontal therapy on the cytokine profile in gingival crevicular fluid of breast cancer patients with periodontitis undergoing chemotherapy.

OBJECTIVE: This study evaluated the effect of non-surgical periodontal therapy (NSPT) on the cytokine profile in gingival crevicular fluid (GCF) in patients with breast cancer and periodontitis. METHODS: Forty patients were allocated into the periodontitis group (P) (n = 20) and breast cancer with periodontitis group (BC/P) (n = 20). Two days before the removal of infectious foci from the oral cavity and NSPT, as well as periodontal reevaluations, C-reactive protein, neutrophils (103µL), and platelets (103µL), were evaluated. The following cytokines in GCF, interleukin (IL)-4, IL-10, IL-2, IL-6, IL-1ß, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and transforming growth factor-ß (TGF-ß) were evaluated by the Luminex assay at baseline, and 45 and 180 days after therapy. Cytokine levels were analyzed for correlations with the clinical parameters: clinical attachment level (CAL), probing depth (PD), bleeding on probing (BOP), and plaque index (PI). RESULTS: After NSPT, IL-2, TNF-α, and TGF-ß were downregulated (p<0.05) in the BC/P. In the P group, INF-γ, IL-2, and TNF-α were downregulated (p<0.05), and TGF-ß was increased (p<0.05). At 180 days, IL-6 in GCF was significantly positively correlated with PD and CAL (r=0.45, r=0.56) in the BC/P (p<0.05). In the P group, IL-1ß in GCF was positively correlated with PD and CAL (r=0.56, r=0.59) at 45 days (p<0.05). CONCLUSION: NSPT, before the start of chemotherapy, helps to reduce the inflammatory markers associated with the activity of periodontal disease, favoring a less inflammatory pattern, to avoid the exacerbation of periodontitis.

Uterine serous carcinoma.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.

Analysis of ovarian cancer cell secretome during epithelial to mesenchymal transition reveals a protein signature associated with advanced stages of ovarian tumors.

Ovarian cancer (OvCA) is the most lethal neoplasia among gynecologic malignancies and faces high rates of new cases particularly in South America. In special, the High Grade Serous Ovarian Carcinoma (HGSC) presents very poor prognosis with deaths caused mainly by metastasis. Among several mechanisms involved in metastasis, the Epithelial to Mesenchymal Transition (EMT) molecular reprogramming represents a model for latest stages of cancer progression. EMT promotes important cellular changes in cellular adhesion and cell-cell communication, which particularly depends on the paracrine signaling from neighbor cells. Considering the importance of cellular communication during EMT and metastasis, here we analyzed the changes in the secretome of the ovarian cancer cell line Caov-3 induced to EMT by Epidermal Growth Factor (EGF). Using a combination of GEL-LC-MS/MS and stable isotopic metabolic labelling (SILAC), we identified up-regulated candidates during EMT as a starting point to identify relevant proteins for HGSC. Based on public databases, our candidate proteins were validated and prioritized for further analysis. Importantly, several of the protein candidates were associated with cellular vesicles, which are important to the cell-cell communication and metastasis. Furthermore, the association of candidate proteins with gene expression data uncovered a subset of proteins correlated with the mesenchymal subtype of ovarian cancer. Based on this relevant molecular signature for aggressive ovarian cancer, supported by protein and gene expression data, we developed a targeted proteomic method to evaluate individual OvCA clinical samples. The quantitative information obtained for 33 peptides, representative of 18 proteins, was able to segregate HGSC from other tumor types. Our study highlighted the richness of the secretome and EMT to reveal relevant proteins for HGSC, which could be used in further studies and larger patient cohorts as a potential stratification signature for ovarian cancer tumor that could guide clinical conduct for patient treatment.

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

BACKGROUND: PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. METHODS: Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. RESULTS: In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40. CONCLUSIONS: The PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer.

Preliminary Results of Non-Surgical Periodontal Treatment in Patients With Breast Cancer Undergoing Chemotherapy.

BACKGROUND: Although priority is often given to treat the cancer itself, focus should also be directed to prevention and improvement of oral complications that may occur as a result of cancer and/or its treatment. This study compares periodontal treatment results in healthy patients and patients with breast cancer undergoing chemotherapy by monitoring clinical conditions and C-reactive-protein (CRP) levels. METHODS: Thirty-five participants were allocated to one of two groups: patients with periodontitis (P) (n = 18) and patients with breast cancer and periodontitis (CAN/P) (n = 17). The following clinical parameters were assessed at baseline and 45, 90, and 180 days after non-surgical periodontal treatment (NSPT): 1) probing depth (PD); 2) clinical attachment level (CAL); 3) plaque index (PI); 4) gingival index (GI); 5) CRP; and 6) complete blood count. Clinical parameters and CRP levels were statistically analyzed. RESULTS: P and CAN/P groups presented a statistically significant decrease in PD after NSPT at 45, 90, and 180 days compared with baseline (P <0.05). There was a CAL gain in the P group and a significant reduction in PI and GI at 45, 90, and 180 days for both groups (P <0.05). At 180 days after NSPT treatment, the CAN/P group showed a higher number of residual pockets (P <0.05) compared with the P group (46.48 ± 26.80 and 7.58 ± 7.40, respectively). The P group demonstrated a significant reduction in CRP levels at 45 and 180 days after NSPT compared with baseline (P <0.05), whereas this reduction was not observed in the CAN/P group. CONCLUSION: Patients with breast cancer who were undergoing chemotherapy responded to periodontal non-surgical therapy, although with less favorable results than patients with periodontitis without cancer, and may require additional or adjunctive periodontal treatments.

The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin.

Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Δ11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo Furthermore, spliceosome inhibitors reduced BRCA1-Δ11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. Cancer Res; 76(9); 2778-90. ©2016 AACR.

Social isolation in women with endometriosis and chronic pelvic pain.

OBJECTIVE: To evaluate the perceptions of women with endometriosis and chronic pelvic pain regarding their social ties. METHODS: A qualitative study was undertaken of women with chronic pelvic pain and endometriosis. Focus groups discussions among four to six participants were performed until saturation at the Clinics Hospital of Ribeirão Preto Medical School, Ribeirão Preto, southwest Brazil, between February 2013 and January 2014. Transcripts were analyzed according to the grounded theory approach and the emerging categories were coded using the WebQDA platform. RESULTS: Six focus group discussions took place, with a total of 29 patients. Social isolation was the main emerging theme. Social isolation was associated with a lack of understanding about endometriosis symptoms and with resignation in face of recurrent pain episodes. Avoiding partner intimacy and isolation from family and friends were components of social isolation. CONCLUSION: Women with endometriosis develop progressive social isolation after the onset of chronic pelvic pain. This finding is important for the multidisciplinary management of the disease.

Anaesthetic injection versus ischemic compression for the pain relief of abdominal wall trigger points in women with chronic pelvic pain.

BACKGROUND: Chronic pelvic pain is a common condition among women, and 10 to 30 % of causes originate from the abdominal wall, and are associated with trigger points. Although little is known about their pathophysiology, variable methods have been practiced clinically. The purpose of this study was to evaluate the efficacy of local anaesthetic injections versus ischemic compression via physical therapy for pain relief of abdominal wall trigger points in women with chronic pelvic pain. METHODS: We conducted a parallel group randomized trial including 30 women with chronic pelvic pain with abdominal wall trigger points. Subjects were randomly assigned to one of two intervention groups. One group received an injection of 2 mL 0.5 % lidocaine without a vasoconstrictor into a trigger point. In the other group, ischemic compression via physical therapy was administered at the trigger points three times, with each session lasting for 60 s, and a rest period of 30 s between applications. Both treatments were administered during one weekly session for four weeks. Our primary outcomes were satisfactory clinical response rates and percentages of pain relief. Our secondary outcomes are pain threshold and tolerance at the trigger points. All subjects were evaluated at baseline and 1, 4, and 12 weeks after the interventions. The study was conducted at a tertiary hospital that was associated with a university providing assistance predominantly to working class women who were treated by the public health system. RESULTS: Clinical response rates and pain relief were significantly better at 1, 4, and 12 weeks for those receiving local anaesthetic injections than ischemic compression via physical therapy. The pain relief of women treated with local anaesthetic injections progressively improved at 1, 4, and 12 weeks after intervention. In contrast, women treated with ischemic compression did not show considerable changes in pain relief after intervention. In the local anaesthetic injection group, pain threshold and tolerance improved with time in the absence of significant differences between groups. CONCLUSION: Lidocaine injection seems to be better for reducing the severity of chronic pelvic pain secondary to abdominal wall trigger points compared to ischemic compression via physical therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00628355. Date of registration: February 25, 2008.

Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer.

BACKGROUND: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. METHODS: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. FINDINGS: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. INTERPRETATION: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.

Limitations of three-dimensional power Doppler angiography in preoperative evaluation of ovarian tumors.

BACKGROUND: This study describes the accuracy of three-dimensional power Doppler (3D-PD) angiography as secondary method for differential diagnosis of ovarian tumors. METHOD: Seventy-five women scheduled for surgical removal of adnexal masses were assessed by transvaginal ultrasound. Ovarian tumors were classified by IOTA simple rules and two three-dimensional blocks were recorded. In a second step analyses, a 4 cm(3) spherical sample was obtained from the highest vascularized solid area of each stored block. Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) were calculated. The repeatability was assessed by concordance correlation coefficient (CCC) and limits of agreement (LoA), and diagnostic accuracy by area under ROC curve. RESULTS: IOTA simple rules classified 26 cases as benign, nine as inconclusive and 40 as malignant. There were eight false positive and no false negative. Among the masses classified as inconclusive or malignant by IOTA simple rules, the CCCs were 0.91 for VI, 0.70 for FI, and 0.86 for VFI. The areas under ROC curve were 0.82 for VI, 0.67 for FI and 0.81 for VFI. CONCLUSIONS: 3D-PD angiography presented considerable intraobserver variability and low accuracy for identifying false positive results of IOTA simple rules.

Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer.

PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model. RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality. CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.

Abdominal myofascial pain syndrome must be considered in the differential diagnosis of chronic pelvic pain.

Chronic pelvic pain is lower abdominal pain lasting at least 6 months, occurring continuously or intermittently and not associated exclusively with menstruation or intercourse. The involvement of the musculoskeletal system in chronic pelvic pain has been increasingly demonstrated. However, few studies exclusively examining abdominal myofascial pain syndrome as a cause of chronic pelvic pain in women are available. Therefore the objective of this manuscript is to describe the association between abdominal myofascial pain syndrome and chronic pelvic pain in women, and comment on methods for diagnosis and therapeutic options. There is evidence that the musculoskeletal system is compromised in some way in most women with chronic pelvic pain and that in 15% of these cases chronic pelvic pain is associated with abdominal myofascial pain syndrome but the scarcity of published data impairs the definition of protocols for the diagnosis and treatment of this disease. Abdominal myofascial pain syndrome is a highly prevalent disease associated with CPP, and because of this physicians should get used to make a precise and early diagnosis in order to avoid additional and unnecessary investigation.

Expression of p63 differs in peritoneal endometriosis, endometriomas, adenomyosis, rectovaginal septum endometriosis, and abdominal wall endometriosis.

CONTEXT: Although there is evidence that endometriosis results from basal endometrium dislocation, the underlying biology is not fully understood. One protein that plays an important role in regulating epithelial proliferation and differentiation is the 63-kDa membrane protein (p63), which is also a marker of basal and reserve cells in the female genital tract. OBJECTIVE: To determine whether p63 is expressed differently in peritoneal endometriosis, endometriomas, and adenomyosis, as well as in deep endometriotic nodules of the rectovaginal septum and abdominal wall. DESIGN: This study includes a prospective series of consecutive patients (Canadian Task Force classification II-2) from a tertiary care university hospital. Specimens collected from 83 patients (15 peritoneal endometriosis specimens, 22 endometrioma specimens, 36 adenomyosis specimens, and 10 rectovaginal septum/abdominal wall specimens) were evaluated. Diagnostic and operative laparoscopies or laparotomies were performed, and tissue samples were obtained. Immunohistochemistry was used to evaluate p63 expression. RESULTS: Positivity for p63 was detected in 93.3% of the peritoneal endometriosis specimens, 81.8% of the endometrioma specimens, 36.1% of the adenomyosis specimens, and none of the rectovaginal/abdominal wall endometriosis specimens (P < .001). Distribution of p63 immunostaining in the positive specimens was homogeneous. CONCLUSIONS: Endometriotic lesions express p63 differently, and some retain the basal/reserve cell immunophenotype. Nevertheless, it remains unclear whether the lack of p63 expression in some lesions is related to the extent of the disease, to its clinical behavior, or to exacerbation of the accompanying symptoms.

Hysteroscopic appearance of malignant and benign endometrial lesions: a case-control study.

OBJECTIVE: To analyze hysteroscopic appearance of benign and malignant endometrial lesions in order to identify patterns to estimate the risk of malignance. STUDY DESIGN: Matched case-control study; two controls per case. The cases were 21 women (age range 40-90 years, median 63) with histologically confirmed endometrial malignancy, and the control group 42 women submitted to diagnostic hysteroscopy for benign lesions (age range 37-81 years, median 57). RESULTS: Hysteroscopic findings associated with malignancy were papillary aspect (OR 26.0, 95%CI 6.4-105.3), size>1/2 uterine cavity (OR 22.0, 95%CI 5.1-95.8), irregular surface (OR 8.0, 95%CI 2.7-23.2), mixed color (OR 10.0, 95%CI 3.6-28.0), diffuse vascular arrangement (OR 5.3, 95%CI 1.3-21.5), little branched vessels (OR 15.0, 95%CI 3.0-74.9), and discordance between the main vascular axe and the direction of the lesion growth (OR 37.0; 95% CI 10.7-128.3). Ulcerated surface and anarchic vascular aspect were present only in malignant cases. CONCLUSION: The analyzes of general aspect, size, surface, color, vascular arrangement and vascular aspect allowed the estimation of the risk of malignancy, and the identification of points for targeted sampling.