Atypical Hyperplasia Group Research Articles

Diagnostic, prognostic, and predictive importance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and carcinoma.

Inflammation has an important role in the progression of endometrial carcinoma. The aim of this study is to find the association between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and endometrial carcinoma. The study also focuses on the association of CA125, NLR, and PLR with histopathological parameters in endometrial carcinoma that are of prognostic importance. This is a prospective cross-sectional study on 57 biopsy-proven cases of endometrial hyperplasia and carcinoma conducted over a period of two years. The NLR, PLR, and CA125 were calculated and recorded in all the 57 cases. The 57 cases were divided into three groups: endometrial hyperplasia without atypia group which included 36 cases, endometrial atypical hyperplasia group which included 10 cases, and the endometrial carcinoma group which included 11 cases. Comparison was done between the groups, and parity, NLR, PLR, and CA125 were found to be significant, but patient age and postmenopausal status were not significant. NLR, PLR, and CA125 were found to increase with higher grade, pT-stage, and nodal stage for the endometrial carcinoma cases. NLR, PLR, and CA125 were marginally increased or normal in the case of endometrial hyperplasia without atypia and endometrial atypical hyperplasia, while they were significantly increased in endometrial carcinoma, and also correlated with an increase in grade, pT-stage, and nodal stage. Hence, these can be considered for additional screening as diagnostic, prognostic, and predictive markers in case of abnormal uterine bleeding with endometrial pathology.

The impact of previous conservative treatment of atypical hyperplasia on pregnancy outcomes after IVF/ICSI-embryo transfer: a propensity score-matched retrospective cohort study.

Do women have worse pregnancy and neonatal outcomes of IVF/ICSI-fresh embryo transfer (ET) after conservative treatment of atypical hyperplasia (AH)? AH has no impact on live birth but is associated with increased risks of pregnancy loss and preterm delivery (PTD). AH is a precancerous lesion of endometrial cancer. Several recognized AH risk factors include nulliparity, increased body mass index, ovulation disorders, diabetes mellitus, and others. As such, patients are suggested to attempt conception upon achieving AH regression. Recently, successful pregnancies with IVF/ICSI have been increasingly reported. Forty-two patients with AH regression and 18700 women with no evidence of endometrial abnormality, who underwent their first autologous oocytes' retrieval and fresh ET cycles of IVF/ICSI in the Center for Reproductive Medicine, Shandong University, from May 2008 to July 2021, were retrospectively enrolled. First, 42 AH patients were propensity score matched with control women (n = 168) at a 1:4 ratio. Reproductive outcomes and maternal/neonatal complications were compared between the matched pairs. Binary logistic regression analyses were conducted to assess odds ratios (ORs) of AH for live birth, pregnancy loss, and PTD from AH women and all 18700 eligible controls. Patients with AH achieved a numerically lower live birth rate (LBR) as compared to the matched controls, but without significant difference (26% versus 37%, P = 0.192). However, compared with the matched controls, AH patients showed significantly higher rates of pregnancy loss (52% versus 21%, P = 0.003) and PTD (45% versus 16%, P = 0.041). Further analyses revealed a statistically significantly increased rate of late pregnancy loss (17% versus 3%, P = 0.023), but not early miscarriage (35% versus 18%, P = 0.086), in the AH group. Furthermore, after correcting for potential confounders, the likelihood of a live birth in AH patients narrowly failed to be statistically significantly different from controls (adjusted OR [aOR]: 0.51, 95% CI: 0.25-1.04, P = 0.064). Nonetheless, the logistic regression reconfirmed that AH was an independent risk factor for pregnancy loss (aOR: 3.62, 95% CI: 1.55-8.46, P = 0.003), late pregnancy loss (aOR: 9.33, 95% CI: 3.00-29.02, P < 0.001), and PTD (aOR: 5.70, 95% CI: 1.45-22.38, P = 0.013). Selection bias was an inherent drawback of this study. First, because of the low AH prevalence among women receiving IVF/ICSI treatment, and consequently, limited sample size, the relationship between AH with LBR and adverse complications might be concealed and underestimated. Hence, the results should be interpreted cautiously. Similarly, the impacts of diverse clinical features of AH patients on the pregnancy outcomes need further studies in a larger population. Second, although most data used in this study were obtained by reviewing the medical records, missing data did exist and so did the recall bias. Third, although the propensity score matching and multivariable logistic models were performed collectively in order to minimize potential confounders between AH and controls, the intrinsic disadvantages of the retrospective nature of this study could not be avoided completely, and additional confirmation bias might be induced with reduplication of statistical analyses. Our results highlight the necessity of adequate counseling and intensive pregnancy monitoring for AH individuals and their families. This work was supported by grants from the National Key Research & Developmental Program of China (2022YFC2703800), the Natural Science Foundation of Shandong Province (ZR2022MH009), and Projects of Medical and Health Technology Development Program in Shandong Province (202005010520, 202005010523). There are no conflicts of interest to declare. N/A.

Use of clinicopathological factors to predict prognosis of fertility-sparing treatment for endometrial endometrioid carcinoma and atypical hyperplasia.

The incidence of endometrial endometrioid carcinoma (EEC) has been gradually increasing over the past decade. Fertility-sparing therapy with progestin is a treatment option for EEC or endometrial atypical hyperplasia (AH). The present study evaluated the role of numerous prognostic factors following fertility-sparing therapy for EEC or AH. Furthermore, the present study assessed the strength of various clinicopathological indicators for the prediction of treatment efficacy. A retrospective analysis was performed of patients with EEC and AH who received fertility-sparing therapy between August 2013 and September 2021 at Peking University People's Hospital (Beijing, China). Endometrial specimens were obtained from each patient after 3 months of treatment and at the end of the fertility-sparing therapy, before treatment efficacy and prognosis were evaluated using the χ2 test. Furthermore, the protein expression levels of EEC biomarkers, such as estrogen receptor (ER), progesterone receptor (PR), paired box 2 (PAX2), PTEN and p53 were assessed using immunohistochemistry. The overall complete response (CR) rate of fertility-sparing treatment in the EEC group was 67.39% (31/46), whereas that in the AH group was 86.49% (32/37). The difference between the CR rates in the EEC and AH groups was statistically significant (P<0.05). There was no association between prognosis after treatment and ER, PAX2, PTEN or Ki-67 expression in the initially untreated AH or EEC groups. However, tissues with >50% positive PR expression were demonstrated to have a higher CR rate compared with those with ≤50% positive PR expression in both the EEC and AH groups. Furthermore, the PAX2-positive group tended to demonstrate higher CR rates compared with the PAX2-negative group in the patients with EEC. In conclusion, these data suggested that fertility-sparing therapy is effective for patients with EEC and AH who wish to remain fertile after treatment. Specifically, in the AH group, a higher proportion of patients achieved a CR whilst also achieving this more rapidly. Furthermore, PR was demonstrated to be a useful marker for the evaluation of EEC and AH.

Value of endometrial thickness for the detection of endometrial cancer and atypical hyperplasia in asymptomatic postmenopausal women

BackgroundThe role of transvaginal sonography (TVS) in screening endometrial cancer and hyperplasia is significant in postmenopausal women. The objective of this study is to determine the endometrium thickness (ET) cut-off to distinguish premalignancy and malignancy in asymptomatic postmenopausal women.MethodsWe retrospectively evaluated data of 968 eligible patients among 2537 asymptomatic postmenopausal women with ET ≥ 5 mm examined by TVS who were subjected to hysteroscopy and endometrial biopsy between January 1, 2017, and June 30, 2020 in an urban tertiary specialized hospital in China. The patients were divided into two groups according to the pathology outcomes: benign, and atypical hyperplasia (AH) and endometrial carcinoma (EC). The risk factors and the optimal cut-off of ET for detecting AH and EC were determined by logistic regression analysis and receiver operating characteristic curve.Results2537 patients were offered hysteroscopy during a 42-month period. Finally, 968 patients were included for further analysis. Of these, 8 (0.8%) women were diagnosed with EC and 5 (0.5%) women with AH. The mean ET of AH and EC group was substantially higher than that in benign group (10.4 mm vs. 7.7 mm, P < 0.05). ET was significantly correlated with AH and EC shown by logistic regression analysis with an odds ratio (OR) of 1.252 (95% confidence interval [CI] 1.107–1.416, P < 0.001). The optimal cut-off value for AH and EC was found to be 8 mm with the maximum AUC of 0.715 (95% CI 0.686–0.743, P < 0.001), with a sensitivity of 0.846, a specificity of 0.609, positive likelihood ratio (LR+) of 2.164 and negative likelihood ratio (LR−) of 0.253.ConclusionAn ET cut-off of ≥ 8 mm shows a reasonable performance to detect AH and EC in asymptomatic postmenopausal women, thereby avoiding more invasive endometrial biopsy.

Simultaneous FTIR and Raman Spectroscopy in Endometrial Atypical Hyperplasia and Cancer.

Currently, endometrial carcinoma (EC) is the most common genital cancer in high-income countries. Some types of endometrial hyperplasia (EH) may be progressing to this malignancy. The diagnosis of EC and EH is based on time consuming histopathology evaluation, which is subjective and causes discrepancies in reassessment. Therefore, there is a need to create methods of objective evaluation allowing the diagnosis of early changes. The study aimed to simultaneously asses Fourier Transform Infrared (FTIR) and Raman spectroscopy combined with multidimensional analysis to identify the tissues of endometrial cancer, atypical hyperplasia and the normal control group, and differentiate them. The results of FTIR and Raman spectroscopy revealed quantitative and qualitative changes in the nucleic acid and protein in the groups of cancer and atypical hyperplasia, in comparison with the control group. Changes in the lipid region were also observed in Raman spectra. Pearson correlation coefficient demonstrated a statistically significant correlation between Raman spectra for the cancer and atypical hyperplasia groups (0.747, p < 0.05) and for atypical hyperplasia and the controls (0.507, p < 0.05), while FTIR spectra demonstrated a statistically significant positive correlation for the same group as in Raman data and for the control and cancer groups (0.966, p < 0.05). To summarize, the method of spectroscopy enables differentiation of atypical hyperplasia and endometrial cancer tissues from the physiological endometrial tissue.

Multiple cytokine profiling in serum for early detection of gastric cancer.

AIMTo investigate the value of multiparameter joint analysis in the early diagnosis of gastric cancer (GC) in clinical practice.METHODSConcentrations of CEA, CA724 and three kinds of cytokines (TNF-α, IL-6 and IL-8) in 176 GC patients, 117 atypical hyperplasia patients, and 204 healthy control individuals were used for building the diagnostic model, then 58 GC patients, 41 atypical hyperplasia patients, and 66 healthy control individuals were enrolled independently. The joints of the indicators were analyzed by binary logistic regression analysis method.RESULTSFor discriminating the healthy control group and the GC group, IL-6 had the best diagnostic value, and the area under curve (AUC) of joint analysis was 0.95 (0.93-0.97). For the early stage and advanced stage GC, the AUC were 0.95 (0.92-0.98) and 0.95 (0.92-0.97). For discriminating the atypical hyperplasia group and GC group, CA724 had the best diagnostic value, and the AUC of joint analysis was 0.97 (0.95-0.99). For the early stage and advanced stage GC groups, the AUC were 0.98 (0.96-0.99) and 0.96 (0.94-0.98). After evaluation, for discriminating the GC, early stage GC and advanced cancer group from the healthy control group, the diagnostic sensitivity was 89.66%, 84.21% and 92.31%, respectively, and the specificity was 92.42%, 90.91% and 90.91%. For discriminating the GC, early stage GC and advanced cancer groups from the atypical hyperplasia group, the diagnostic sensitivity was 87.93%, 78.95% and 92.31%, respectively, and the specificity was 87.80%, 85.37% and 90.24%.CONCLUSIONWe have built a diagnostic model including CEA, CA724, IL-6, IL-8, and TNF-α. It may provide potential assistance as a screening method for the early detection of GC.

The expression level of TRAF1 in human gastric mucosa is related to virulence genotypes of Helicobacter pylori

Objective. To investigate the expression level of tumor necrosis factor receptor-associated factor 1 (TRAF1) in gastric mucosa tissue in patients infected with Helicobacter pylori (H. pylori) and to analyze the relationship between TRAF1 expression and H. pylori virulence. Methods. Gastric tissue samples were collected from patients with gastritis, atrophic gastritis, intestinal metaplasia with atypical hyperplasia, and gastric cancer. The expression level of TRAF1 in each group was analyzed by real-time polymerase chain reaction (PCR) and Western blot analysis. Virulence genotypes of H. pylori were determined by PCR. Results. Significant differences in TRAF1 mRNA levels were observed between the gastritis and gastric cancer groups, and the atrophic gastritis and gastric cancer groups (p < 0.05). Moreover, significant differences in TRAF1 protein levels were observed between the gastritis and intestinal metaplasia with atypical hyperplasia groups, between the gastritis and gastric cancer groups, and between the atrophic gastritis and gastric cancer groups (all p < 0.05). The virulence genotypes of cytotoxin-associated gene A (cagA), vacAs1, and vacAm1 were more frequent in the TRAF1 high-level group than in the TRAF1 low-level group (p < 0.05). Conclusion. Higher TARF1 expression level is associated with infection by CagA+/vacAs1+/m1+ virulent H. pylori strains and may promote the proliferation of gastric mucosal cells and induce gastric cancer.

The c-myc mRNA and helicobacter pylori infection and the relationship between the programmed cell death in the with Gastric cancer in the patients with gastric cancer

Objective To discuss different stomach trouble change occurred in the process of development until the progression in patients with c-myc mRNA expression in correlation with helicobacter pylori (Hp) infection and its relationship with gastric tissue programmed cell death.Methods By real-time fluorescent quantitative reverse transcription-olymerase chain reaction (FQ-PCR) to detect 72 cases of chronic superficial gastritis (CSG),55 cases of chronic atrophic gastritis (the CAG),52 cases of intestinal metaplasia (IM),46 cases of atypical hyperplasia (AH),65 cases of gastric cancer (GC) group (CSG group,respectively,the CAG group,IM,AM group,AH,the GC group) in the c-myc mRNA expression;Rapid enzymatic urea,Warthin Starry silver staining and toluidine blue staining assay for gastric mucosa Hp infection;In situ end labeling (TUNEL) method to detect gastric mucosal cell apoptosis index (AI).Results CSG group,the CAG group,IM,AM group,AH,the GC group c-myc in gastric mucosa tissue mRNA positive example were 21.5％ (7/31),31.0％ (8/27),41.0％ (10/26),59.1％ (14/24) and 69.1 (23/33),c-myc relative mRNA expression levels were 0.089 ± 0.002,0.01 13 ± 0.014 mm,0.168 ±0.028,0.226,0.367 ±0.037 mm,0.040 mm IM,AH group,GC group c-myc amount of mRNA expression were higher than in CSG,the CAG group (P ＜ 0.01),the AH group is higher than the IM group (P ＜0.01),the GC group higher than IM,AH group (P ＜0.01).C-myc mRNA expression quantity and negatively correlated with gastric mucosa cells AI (rs =-0.700,P ＜0.05) ;IM,AH group,GC group Hp positive patients with gastric mucosa cell c-myc mRNA expression were higher than Hp negative patients (P ＜0.05 or 0.01).Conclusion In the process of the gastric mucosal canceration,Hp infection can increase gastric mucosa cell c-myc mRNA expression,and inhibition of special-shaped programmed cell death (apoptosis) and play a role of cancer. Key words: C-myc mRNA ; Tumor suppressor gene; Apoptosis

Study of claudin-4 in the diagnosis and treatment of endometrial carcinoma

To clarify the role of claudin-4 in endometrial tumorigenesis and explore claudin-4 be as potentially useful agent in the treatment of endometrial carcinoma. The expression of claudin-4 in 62 endometrioid endometrial carcinoma (EEC), 30 atypical hyperplasia endometrial tissue and 60 human normal endometrium was determined using immunohistochemistry and real-time PCR. Ninety female BALB/c mice were transplanted with Ishikawa endometrial cancer cells, which were divided into three groups with different intraperitoneal treatments with cisplatin, paclitaxel and saline solution. After the observation period, the tumors were extracted and stained with monoclonal antibody against claudin-4. The messenger RNA expression of claudin-4 was also detected using real-time PCR. Among the EEC samples, 34% (21/62) showed medium staining for claudin-4 and 66% (41/62) showed intense staining. In atypical hyperplasia group, 27% (8/30) showed weak staining, 53% (16/30) showed medium staining and 20% (6/30) showed intense staining for claudin-4. Of the normal endometrial tissue, 47% (28/60) showed weak staining and 53% (32/60) showed no staining for claudin-4. According to real-time PCR, the relative quantity of claudin-4 was 170 ± 12 in EEC group, 89 ± 15 in atypical hyperplasia group and 18 ± 3 in normal endometrium. Compared with those in atypical hyperplasia group and normal endometrium group, the protein and mRNA expression of claudin-4 were significantly increased in the group of EEC (all P < 0.05). In the study of Ishikawa xenografts, no significant changes in tumor volume and claudin-4 expression were shown in paclitaxel group compared with that in the control group. Nevertheless, a significant reduction of the tumor growth and a significant decrease in claudin-4 expression were observed in cisplatin group. After cisplatin treatment, the tumor volume was significantly decreased [(0.51 ± 0.21) versus (0.73 ± 0.12) cm(3)], and the mRNA expression of claudin-4 was also significantly decreased (153 ± 35 versus 273 ± 27). These results demonstrate that claudin-4 is strongly expressed in EEC, which may be a useful biomarker to monitor the effects of chemotherapy in patients with endometrial carcinoma.

UbcH10 Expression in Benign, Hyperplastic, and Malignant Endometrial Curetted Materials

The aim of this study was to investigate the role of UbcH10 expression in the differential diagnosis of benign, hyperplastic, and malignant endometrial tissues and also the relationship of UbcH10 with the clinicopathologic parameters of malignant cases. A tissue microarray was performed for 81 endometrial curettage biopsies, which histological diagnosis had demonstrated to be 13 cases of proliferative endometrium, 7 cases of disordered proliferative endometrium, 5 cases of complex atypical hyperplasia, 24 cases of nonatypical hyperplasia, and 32 cases of endometrioid adenocarcinoma. Expression of UbcH10 was assessed by immunohistochemistry. When groups were compared according to UbcH10 percentages and scores, a statistically significant difference was found only between the carcinoma group and the other groups, except the complex atypical hyperplasia group (P < .05). In the malignant group, UbcH10 percentages and scores were only significantly related to age. There was no significant association between UbcH10 expression and tumor grade and stage. Overexpression of UbcH10 may be a useful indicator of endometrial carcinoma. UbcH10 also deserves further evaluation in the detection of prognostic mean and also for its role in endometrial carcinogenesis.

Levonorgestrel-releasing intrauterine system (LNG-IUS) as an effective treatment option for endometrial hyperplasia: a 15-year follow-up study

The levonorgestrel-releasing intrauterine system may represent an effective treatment option in >85% of endometrial hyperplasia cases, but histologic regression during and/or at the end of treatment does not assure stable recovery. We recommend periodic endometrial samplings for at least the first 2 years of follow-up and long-term clinical surveillance thereafter.

Relationship between nasal inverted papilloma and human papillomavirus subtypes

To study the distribution of human papillomavirus (HPV) subtypes in nasal inverted papilloma (NIP), and to evaluate the relationship between HPV and NIP. Twenty-one HPV subtypes were detected in paraffin-embedded tissues of 101 cases of NIP by flow through hybridization and gene chip (HybriMax), 24 cases of normal nasal mucosa were used as controls. HPV positive rates of NIP were 64.36% (65/101). Benign NIP group, NIP with atypical hyperplasia group, NIP with cancerous group of HPV positive rates were 59.7% (46/77), 81.8% (18/22) and 50% (1/2) respectively. The control group was negative (0/24). The comparison between NIP group and control group was statistically significant (chi(2) = 32.178, P < 0.05). Benign NIP group and NIP with atypical hyperplasia group were compared, but no statistically significance (chi(2) = 3.649, P = 0.056) was found. The constituent ratio of benign NIP group and NIP with atypical hyperplasia group in high, low-risk HPV subtypes infections was compared, a statistically significance (chi(2) = 10.412, P < 0.05) was found. The occurrence of NIP was related with HPV infection. High-risk HPV subtype infections or multiple infections will prompt benign NIP to NIP with atypical hyperplasia. Understanding the distribution of HPV subtypes in the NIP is helpful to predict the clinical behavior.

Inspection on angiogenesis in malignant transformation of breast tumor by ultrasound contrast and quantitative analysis

To study the effects of angiogenesis on tumorigenesis and the progression of breast carcinoma and precancerous lesion. Real time ultrasound contrast enhanced microvascular imaging (MVI) and time-intensity curve quantitative analysis were conducted on 30 normal controls, 30 cases with simple hyperplasia, 30 cases with atypical hyperplasia (AH), 20 cases with intraductal carcinoma in situ, and 50 cases with invasive ductal carcinoma, all female. Specimens of breast tissues were obtained and immunohistochemistry was used to detect the expression of CD34, a marker of vascular endothelial cells, and vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR. With the progression of malignant transformation of breast tissue, the expression levels of VEGF and Flk-1/KDR increased gradually, the framework of the vessels became disordered, the levels of MVD and the perfusion parameters, such as peak intensity (PI), area under the curve (AUC), and wash-out time (WOT), increased. Obvious changes in these parameters began since the AH stage. There were not significant differences in the PI, AUC, and WOT levels between the groups of AH and in situ cancer, however, the VEGF and Flk-1/KDR levels of the in situ carcinoma group were significantly higher than those of the AH group (both P<0.05). Angiogenesis plays an important role in the development of breast carcinoma. Contrast MVI and the main perfusion parameters reflect the rule of angiogenesis activity changing in different precancerous lesions, and can be used as non-invasive methods to screen high risk population.

Expression and activation of insulin receptor substrate-1 in endometrial carcinoma

To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma. Sixty-three endometrial carcinoma (EC) patients, 21 endometrial atypical hyperplasia (AHE) patients and 22 normal control (NE) entered this study. Their clinical information were collected. Fasting serum C-peptide concentration was measured. Expression of IRS-1 in endometrium was examined by RT-PCR and western blot. Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1. C-peptide concentration in EC group was higher than that in NE group [(3.2 +/- 1.1) vs (2.5 +/- 0.7) microg/L, P=0.007]. There were no significant differences in IRS-1 mRNA and protein expression among the three groups. Tyrosine phosphorylation of IRS-1 in EC group [(62 +/- 36) %] was higher than that in AHE and NE groups [(53 +/-34)% and (35 +/- 33)%; P=0.048, 0.002]. IRS-1 activation in AHE group was also higher than normal control (P=0.045). IRS-1 activation in endometrioid carcinoma [(69 +/- 33) %] was higher than that in other histological types [(34 +/- 31)%; t=2.300, P=0.025]. IRS-1 tyrosine phosphorylation was significantly higher in patients with advanced stage, high grade, deep myometrial invasion and pelvic lymph node metastasis. IRS-1 activation in endometrium was positively correlated with fasting serum C-peptide concentration (r=0.491, P=0.001). There is excessive activation of IRS-1 in endometrial carcinoma and atypical hyperplasia. Activation of IRS-1 in endometrial carcinoma is related with poor clinical-pathologic features and may be a prognostic predictor for this tumor. Over-activation of IRS-1 may be an intermediate event linking the hyperinsulinemia and endometrial carcinoma.

Expression of vascular endothelial growth factor in different breast tissues and clinical significance thereof

To investigate the differences in the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) count in breast benign affection, breast atypical hyperplasia, and breast carcinoma in situ and to clarify the association of VEGF expression and MVD with the clinicopathological features of these diseases. Immunohistochemistry (SP-method) was used to examine the expression of VEGF and MVD count in 100 samples of breast benign affection (including 35 cases of breast fibroid tumor, 35 cases of breast cystic hyperplasia, and 30 cases of intraductal papilloma), and 15 samples of breast atypical hyperplasia, and 25 samples of breast carcinoma in situ, obtained during operation. The positive rate of VEGF of the breast carcinoma in situ group was 56% , significantly higher than hose of the breast benign affection and breast atypical hyperplasia groups (22% and 33% respectively, P < 0.05). However, there was no significant differences in positive rate of VEGF among breast fibroid tumor, breast cystic hyperplasia, and intraductal papilloma (all P > 0.05). The MVD value of the breast carcinoma in situ group was 20.1 +/- 6.1, significantly higher than those of the breast benign affection group and breast atypical hyperplasia groups (14.3 +/- 3. 5 and 18.5 +/- 3.6 respectively, both P < 0.05). There was no significant differences in MVD value among breast fibroid tumor, breast cystic hyperplasia, and intraductal papilloma (all P > 0.05). In breast tumors, angiogenesis is probably mediated mainly by VEGF. The occurrence and progression of breast cancer may be related with the expression of VEGF.

Expression profile of aquaporin 1 in patients with menorrhagia

To investigate the expression of aquaporin 1 (AQP1) in endometrium of patients with menorrhagia. RT-PCR and immunohistochemistry were carried out in twenty women with normal menstrual cycle to confirm the expression of AQP1 in endometrium and locate it. Then 51 women with menorrhagia and 40 women with normal menstrual cycle were included in the study. RT-PCR and immunohistochemistry were used to examine the expression of AQP1. AQP1 mRNA was expressed in the human endometrium throughout menstruation cycle, which was mainly located in the endothelia of the capillaries and small blood vessels. Quantification of the immunostaining revealed higher density during secretary phase than that in proliferative phase (P<0.01). The staining intensity and density of AQP1-positive microvessel decreased significantly in simple hyperplasia group (P<0.01) and then gradually increased in complex hyperplasia and atypical hyperplasia groups (P<0.001). Decreased expression of AQP1 may lead to disturbed endometrial vascular remodeling and may be involved in the occurrence of menorrhagia.

Results of MRI Screening for Breast Cancer in High-Risk Patients with LCIS and Atypical Hyperplasia

Magnetic resonance imaging (MRI) can detect breast cancer in high-risk patients, but is associated with a significant false-positive rate resulting in unnecessary breast biopsies. More data are needed to define the role of MRI screening for specific high-risk groups. We describe our experience with MRI screening in patients with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS). We retrospectively reviewed data from our high-risk screening program prospective database for the period from April 1999 (when screening MRI was first performed at our institution) to July 2005. Patients with AH or LCIS demonstrated on previous surgical biopsy were identified. All patients underwent yearly mammography and twice yearly clinical breast examination. Additional screening MRI was performed at the discretion of the physician and patient. We identified 378 patients; 126 had AH and 252 had LCIS. Of these, 182 (48%) underwent one or more screening MRIs (mean, 2.6 MRIs; range, 1-8) during this period, whereas 196 (52%) did not. Those who had MRIs were younger (P < 0.001) with stronger family histories of breast cancer (P = 0.02). In MRI-screened patients, 55 biopsies were recommended in 46/182 (25%) patients, with 46/55 (84%) biopsies based on MRI findings alone. Cancer was detected in 6/46 (13%) MRI-generated biopsies. None of the six cancers detected on MRI were seen on recent mammogram. All six cancers were detected in five patients (one with bilateral breast cancer) with LCIS; none were detected by MRI in the AH group. Thus, cancer was detected in 5/135 (4%) of patients with LCIS undergoing MRI. The yield of MRI screening overall was cancer detection in 6/46 (13%) biopsies, 5/182 (3%) MRI-screened patients and 5/478 (1%) total MRIs done. In two additional MRI-screened patients, cancer was detected by a palpable mass in one, and on prophylactic surgery in the other and missed by all recent imaging studies. For 196 non-MRI-screened patients, 21 (11%) underwent 22 biopsies during the same period. Eight of 22 (36%) biopsies yielded cancer in seven patients. All MRI-detected cancers were stage 0-I, whereas all non-MRI cancers were stage I-II. Patients with AH and LCIS selected to undergo MRI screening were younger with stronger family histories of breast cancer. MRI screening generated more biopsies for a large proportion of patients, and facilitated detection of cancer in only a small highly selected group of patients with LCIS.

Outcomes of tamoxifen chemoprevention for breast cancer in very high-risk women: a cost-effectiveness analysis.

To estimate the effects on survival, quality-adjusted survival, and health care costs of using tamoxifen for primary prevention in subgroups of women at very high risk for breast cancer. A decision analysis was performed using a hypothetical cohort of women that included subgroups with atypical hyperplasia, Gail risk greater than 5, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. Data sources were the Breast Cancer Prevention Trial, the Surveillance, Epidemiology, and End-Results program, time trade-off preference ratings, the Group Health Cooperative of Puget Sound, and the United States Health Care Financing Administration. Our model predicted that tamoxifen would prolong the average survival of cohort members initiating use at ages 35, 50, and 60 years by 70, 42, and 27 days, respectively. It would prolong survival even more for those in the higher-risk groups, especially those with atypical hyperplasia (202, 89, and 45 days). Tamoxifen use was also projected to extend quality-adjusted survival by 158, 80, and 50 days in the atypical hyperplasia group. For younger women in the highest risk groups, chemoprevention with tamoxifen was estimated to have cost savings or be cost-effective, both with and without quality adjustments. Chemoprevention with tamoxifen may be particularly beneficial to women with atypical hyperplasia, 5-year Gail model risk greater than 5%, lobular carcinoma-in-situ, or two or more first-degree relatives with breast cancer. The benefits may be greater if tamoxifen is initiated before age 50 years rather than after and if the breast cancer risk reduction conferred by tamoxifen lasts longer than 5 years. For women with a very high risk of invasive breast cancer, chemoprevention with tamoxifen seems to be cost-effective.

Langerhans Cells in Human Papillomaviruses Types 6/11 Associated Laryngeal Papillomas

Ferluga D, Luzar B, Vodovnik A, Poljak A, Cör A, Gale N, KambiČ V. Langerhans cells in human papillomaviruses types 6/11 associated laryngeal papillomas.Some studies have shown a reduced density of Langerhans cells (LCs) within epithelium infected by human papillomaviruses (HPV) types 16/18. However, data on a correlation between HPV types 6/11 infection and LCs have been missing. To solve this problem, we analysed 24 biopsy specimens of laryngeal papillomas, selected randomly, 20 multiple and 4 solitary. The presence of HPV 6 and 11 was proven by polymerase chain reaction (PCR) using 2 different sets of primers in 23 biopsy specimens. Abnormalities of the covering stratified squamous epithelium were graded according to the KambiČ-Gale classification. LCs were immunohistochemically labelled with 2 different antibodies, CD1a and S100. Quantitative analysis was performed to determine the density of LC per mm2 in different grades of epithelial abnormalities covering laryngeal papillomas. Although no statistically significant differences in the mean number of LCs per mm2 of the cross-sectioned epithelium covering laryngeal papillomas were observed comparing simple, abnormal and atypical hyperplasia groups, the mean number of LCs per mm2 in laryngeal papillomas associated with HPV types 6/11 infection substantially exceeded that of the vocal cord surface epithelium in patients with chronic laryngitis.

Breast cancer risk associated with proliferative disease, age at first birth, and a family history of breast cancer.

The authors reevaluated 10,542 consecutive breast biopsies of women who presented at three Nashville hospitals. Median follow-up was 17 years for 3,398 women (84.4% of patients originally selected for follow-up). Breast cancer relative risks associated with no proliferative disease, proliferative disease without atypia, and atypical hyperplasia were 0.80, 1.4, and 4.0 times that for women from the Cancer in Connecticut data base, respectively (adjusted for age at biopsy, year of biopsy, and length of follow-up). Nulliparous women were at increased risk of breast cancer (relative risk = 1.6; 95% confidence interval (CI) = 1.1-2.2). Women who gave birth to their first child before age 21 years had a relative risk of 0.80, with higher cancer risks associated with later age at first birth. The effect of age at first birth on cancer risk followed a similar pattern within the no proliferative disease, proliferative disease without atypia, and atypical hyperplasia groups. Nulliparous women with atypical hyperplasia had a relative risk of 4.9 (95% CI = 2.7-8.9), while women with no proliferative disease who gave birth before age 21 years had a relative risk of 0.50 (95% CI = 0.19-1.3). Nulliparous women with a family history of breast cancer had a relative risk of 2.7 (95% CI = 1.4-5.2). Women with a family history who first gave birth by age 20, between ages 21 and 29, and after age 30 years had relative risks of 0.53, 2.1, and 4.0, respectively (95% CI = 0.08-3.8, 1.1-3.9, and 1.8-9.6, respectively). Breast size had no effect on cancer risk in women without proliferative disease. However, in women with proliferative disease, small, medium, and large breasts were associated with relative risks of 1.2, 1.4, and 2.1, respectively.