The NF-κB pathway mediates lysophosphatidic acid (LPA)-induced VEGF signaling and cell invasion in epithelial ovarian cancer (EOC)

Objectives

Our previous report has implicated the involvement of VEGF-VEGFR-2 h signaling in LPA-induced EOC invasion. However, the mechanism by which LPA regulates VEGF and VEGFR-2 expression remains to be elucidated. In the present study, we systematically examined the signal transduction pathways activated by LPA and further evaluated whether LPA's effect on VEGF-VEGFR-2 signaling and EOC invasion was mediated by the activation of NF-κB pathway.

Methods

Using a signal transduction PathwayFinder PCR array, we examined the expression change of 86 key genes representing 18 signal transduction pathways in DOV13 and SKOV3 cells upon LPA (20 μM) treatment. We also used quantitative PCR, Western blotting and ELISA to evaluate the effect of NF-κB pathway inhibition on VEGF₁₂₁, VEGF₁₆₅ and VEGFR-2 mRNA and protein expression/secretion with or without the presence of LPA (20 μM) in SKOV3. Cell invasion under various treatment conditions was assessed by Matrigel invasion assay and MMP-2 secretion was detected by gelatin zymography.

Results

Our results showed that in both DOV13 and SKOV3, several of the NF-κB pathway components, such as TNF, are consistently activated by LPA stimulation. In addition, treatment with an NF-κB pathway activation inhibitor, at 10 μM, significantly decreased LPA-induced VEGF₁₂₁, VEGF₁₆₅ and VEGFR-2 mRNA expression and VEGF secretion, as well as LPA-induced SKOV3 invasion (p < 0.05). When combined with an EGFR inhibitor, NF-κB pathway inhibition exhibited a significantly stronger effect than used alone (p < 0.05) on reducing LPA-induced VEGF secretion and cell invasion. Additionally, NF-κB inhibition also decreased LPA-induced MMP-2 secretion and MMP-1 expression (p < 0.05).

Conclusions

These results suggest that the NF-κB pathway plays an important role in LPA-induced VEGF signaling and EOC invasion and targeting this pathway may reveal potential therapeutic options for metastatic EOC.     

Expression of 67-kDa laminin receptor was associated with tumor progression and poor prognosis in epithelial ovarian cancer

Objective

67-kDa laminin receptor (67LR) has been identified as a prognostic biomarker for a variety of human cancers. We investigated the clinical significance of 67LR expression and its functional role in epithelial ovarian cancer (EOC).

Methods

67LR expression was evaluated by immunohistochemistry in 62 patients with EOC. We assessed the correlation of 67LR expression with clinical characteristics. In vitro experiment was performed for 67LR with inhibition using siRNA to evaluate its role in cell survival, apoptosis, and invasion in EOC cells.

Results

67LR was predominantly expressed on the cell membrane in the majority of EOC samples (45/62, 73%). 67LR expression was significantly correlated with advanced stage (P = 0.001). Patients with 67LR expression had shorter progression-free survival among all the patients (P = 0.010) and in particular among patients with advanced stages (P = 0.046). When 67LR expression was inhibited by siRNA in EOC cells (HeyA8 and A2780), there was a significant decrease of cell proliferation and invasion as well as increase of apoptosis.

Conclusion

These findings suggest that 67LR expression may play an important role in tumor progression into advanced stage with poor prognosis in EOC and down-regulation of 67LR on tumor cells may be a therapeutic target in those patients.     

Increased matrix metalloproteinases-1,-9 in the uterosacral ligaments and vaginal tissue from women with pelvic organ prolapse

Objectives

To investigate the possible association of increased matrix metalloproteinases (MMPs)-1,-9 with pelvic organ prolapse (POP) and to evaluate whether inflammatory processes contribute to its development.

Study design

Forty women who underwent hysterectomy, 20 with POP grade 2 and above, and 20 without POP, participated in the study. Biopsies from the uterosacral ligaments and vaginal mucosa were obtained from each woman. Each biopsy was sectioned and stained for MMP-1 and MMP-9 by immunohistochemical methods and with hematoxylin and eosin (H&E). MMP-1,-9 expressions were evaluated on the immunostained slides. H&E stained sections were examined for possible inflammatory changes.

Results

A higher stromal (extra-cellular) expression of MMPs-1,-9 was found in POP cases compared with controls in vaginal biopsies (MMP-1: p = 0.004; MMP-9: p = 0.042) as well as in uterosacral ligament biopsies (MMP-1: p = 0.011; MMP-9: p = 0.015). Increased intracellular expression of both MMPs was also demonstrated in fibroblasts in biopsies of women with POP (p < 0.001 for all). Most of these differences persisted after controlling for age. The degree of inflammatory changes reflected by the number of lymphocytes, plasma cells and capillary-sized blood vessels per 10 high power fields, was similar in specimens obtained from women with and without POP.

Conclusions

The expression of MMPs-1,-9 appears to be increased in tissues from women with POP. This supports an association, although not a causal relation, between increased MMPs-1,-9 and POP. Inflammation does not seem to play an important role in the pathogenesis of POP.     

High level of WAVE1 expression is associated with tumor aggressiveness and unfavorable prognosis of epithelial ovarian cancer

Objectives

Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) has been shown to promote cancer invasion and metastasis. However, no evidence has been found to identify the role of WAVE1 in epithelial ovarian cancer (EOC). This study aims to determine the effect of WAVE1 expression and investigate a possible relationship between WAVE1 and prognosis in EOC.

Methods

WAVE1 protein level was measured in 223 EOC specimens by immunohistochemical staining and 46 EOC specimens by Western blot analysis. Expression of WAVE1 in ovarian cancer cell lines was evaluated by Western blot analysis and immunofluorescence. Survival analysis was performed to assess the correlation between WAVE1 expression and survival.

Results

Immunohistochemical staining and Western blot analysis showed that WAVE1 was overexpressed in EOC compared with samples from a non-invasive ovarian tumor and normal ovaries (P < 0.05). Furthermore, expression of WAVE1 was significantly associated with advanced FIGO stage, poor grade, serum Ca-125 and residual tumor size (P < 0.05). By Western blot analysis, WAVE1 expression was detected in four ovarian cancer cell lines. Immunofluorescence was performed to demonstrate WAVE1 expression in SKOV3 and 3AO cell lines. Survival analysis showed that patients with low WAVE1 staining had a significantly better survival compared to patients with high WAVE1 staining (P < 0.05). In multivariate analysis, WAVE1 overexpression, advanced stage and suboptimal surgical debulking were independent prognostic factors of poor survival.

Conclusions

Our present study finds that WAVE1 overexpression is associated with an unfavorable prognosis. WAVE1 is an independent prognostic factor for EOC, which suggests that it is a novel and crucial predictor for EOC metastasis.     

A novel modification of conventional laparoscopic myomectomy using manual assistance for multiple uterine myomas

Objectives

Endometriosis is a common gynaecological disease with clinical symptoms such as chronic pain, infertility and intra-abdominal adhesions. Different theories on the pathogenesis of endometriosis and especially its aggressive subtype with infiltrative growth have been discussed. The objective of this study is to evaluate differences in proliferation and invasive properties of invasive colorectal endometriosis, superficial peritoneal endometriosis and endometrial carcinoma (G1 and G2).

Study design

Paraffin embedded tissues of peritoneal endometriosis, endometriosis of the intestine and endometrial carcinoma from 97 patients were stained immunohistochemically to assess differences in expression patterns of matrix metalloproteinases (MMP-2, MMP-9) as markers of invasion and the marker of proliferation PCNA. MMP expression was evaluated using the Immuno Reactive Score (IRS) (combining positive cell ratio and staining intensity) and PCNA expression was assessed as the percentage of positively stained cells in representative areas.

Results

MMP-2, MMP-9 and PCNA showed differential expression patterns in the different tissues examined. MMP-2 and PCNA expression was stronger in invasive colorectal endometriosis than in superficial peritoneal endometriosis (p = 0.0394). MMP-9, however, was more frequently expressed in peritoneal endometriosis (59.1%) than in colorectal endometriosis (44.4%). This result did not reach statistical significance. When colorectal endometriosis was compared to low grade endometrial carcinoma, proliferation detected by PCNA was significantly higher in endometriosis (p = 0.0008). MMP-2 and MMP-9 showed higher expression in endometrial carcinoma than in endometriosis.

Conclusions

There are obvious differences in expression patterns of MMP-2, MMP-9 and PCNA in different stages of endometriosis and in endometrial cancer. These markers can be helpful to evaluate aggressiveness and invasiveness of endometriosis in different localizations. The results obtained could be of relevance for a better understanding of the pathogenesis of endometriosis and the development of an individual therapy concept.     

Overexpression of c-Abl predicts unfavorable outcome in epithelial ovarian cancer

Objectives

Abelson tyrosine kinase (c-Abl) has been shown to promote solid tumor invasion and metastasis. However, little is known regarding whether c-Abl contributes to the development or progression of epithelial ovarian cancer (EOC). The aims of this study are to determine the expression of c-Abl and investigate a possible relationship between c-Abl and prognosis in EOC.

Methods

c-Abl protein level was evaluated in 137 EOC specimens by immunohistochemical staining and 32 EOC specimens by Western blot analysis. Expression of c-Abl in ovarian cancer cell lines was measured by Western blot analysis and immunofluorescence. Survival analysis was performed to assess the correlation between c-Abl expression and survival.

Results

Immunohistochemical staining and Western blot analysis revealed that c-Abl was overexpressed in EOC compared with samples from a non-invasive ovarian tumor and normal ovaries (P < 0.05). Furthermore, expression of c-Abl was significantly associated with advanced FIGO stage, poor grade, serum Ca-125 and residual tumor size (P < 0.05). By Western blot analysis, c-Abl expression was examined in four ovarian cancer cell lines. Meanwhile, immunofluorescence was performed to show c-Abl expression in SKOV3 and 3AO cell lines. Survival analysis demonstrated that patients with low c-Abl staining had a significantly better survival compared to patients with high c-Abl staining (P < 0.05). In multivariate analysis, c-Abl overexpression, poor grade, advanced stage and suboptimal surgical debulking were independent prognostic factors of poor survival.

Conclusions

Our present study finds that c-Abl overexpression is associated with an unfavorable outcome. c-Abl may be a crucial predictor for EOC metastasis.     

Prognostic value of the copper transporters, CTR1 and CTR2, in patients with ovarian carcinoma receiving platinum-based chemotherapy

Objective

CTR1 and CTR2 are copper transporters that have been associated with platinum sensitivity in several human cancers. We investigated the prognostic significance of CTR1 and CTR2 in women with ovarian carcinoma.

Materials and methods

We evaluated the expression of CTR1 and CTR2 using real-time PCR in 40 women with ovarian carcinoma (IIb = 2, IIIb = 2, IIIc = 30, IV = 6). We compared the expression of CTR1 and CTR2 with participants' clinicopathological findings.

Results

We found lower expression of CTR1 and CTR2 mRNA in ovarian cancer cells against normal ovarian tissue with statistically significant differences (p = 0.018 and 0.011, respectively). High CTR1 expression was a prognostic factor for improved survival after adjusting for age, tumor grade, stage, residual tumor, and CTR2 mRNA expression (HR, 0.35; 95% CI, 0.15-0.84). However, CTR2 expression did not exhibit any prognostic significance. Of the 20 women with elevated CTR1 expression, 17 (85%) were sensitive to platinum-based chemotherapy. Of the 7 women with low CTR1 expression and high CTR2 expression, 6 (85.7%) were resistant to platinum-based chemotherapy and had the shortest progression-free survival of all women in our study sample.

Conclusion

In our sample of 40 women with ovarian carcinoma, high CTR1 expression was significantly associated with sensitivity to platinum-based chemotherapy and longer progression-free survival. Conversely, low CTR1 expression and high CTR2 expression were significantly associated with resistance to platinum-based chemotherapy and the shortest survival.     

Single nucleotide polypmorphisms in ERCC1 are associated with disease progression, and survival in patients with advanced stage ovarian and primary peritoneal carcinoma; a Gynecologic Oncology Group study

Objective

This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy.

Methods

Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS).

Results

The genotype distribution at codon 118 (n = 278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT + TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.49-0.95, p = 0.025). The genotype distribution for C8092A in ERCC1 (N = 280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA + AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR = 1.29, 95% CI = 0.97-1.72, p = 0.077).

Conclusions

The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant.     

BRCA1/2 mutations and expression: response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer

Objective

Our objective was to determine the rate of BRCA1/2 deficiency in platinum-sensitive and platinum-resistant tumors from a cohort of unselect patients with advanced epithelial ovarian cancer (EOH).

Methods

BRCA1/2 mutation analysis was performed in 29 patients with platinum-sensitive EOC and 24 patients with platinum-resistant disease. Germline DNA was analyzed in mutation carriers when normal tissue was available. BRCA expression was ascertained by quantitative rt-PCR. Associations between BRCA mutation status and expression levels and parameters of platinum response were analyzed.

Results

Fifteen of 53 (28.3%) EOC tumors had BRCA1/2 mutations. Twelve mutations were in BRCA1, while 3 involved BRCA2. Of the 12 mutation-carriers with normal tissue available for DNA analyses, 33.3% of the mutations were found to be somatic. Three mutations were novel. The majority of BRCA mutations (73%) were identified in patients with platinum-sensitive disease. In total, 38% of platinum-sensitive tumors were found to have a BRCA mutation, compared to 17% of the platinum-resistant patients. A statistical trend toward platinum-sensitive disease was seen in BRCA mutation carriers (p = 0.079). Nineteen (36%) study patients had some form of BRCA deficiency, and these patients were less likely to have platinum-resistant tumors (OR = 0.29; p value = 0.048).

Conclusions

BRCA mutations occurred more frequently in platinum-sensitive EOC than platinum-resistant disease. The high overall frequency of BRCA deficiency in EOC underscores the importance of tumor profiling as therapies targeting the DNA repair pathway are being investigated.     

Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: a meta-analysis

Objective

To compare the survival outcome between clear cell carcinoma (CCC) and other histological subtypes in epithelial ovarian carcinoma (EOC).

Methods

From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-CCC; 29648) patients from 12 studies meeting the inclusion criteria.

Results

Heterogeneity tests demonstrated significant between-study variation (I² = 92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-CCC (HR; 1.16, 95% CI; 0.85-1.57, random-effects model). Comparing the HR based on stage I + II, and stage III + IV, between CCC and non-CCC, showed that CCC patients had a higher hazard rate for death than those with non-CCC of the ovary (stage I + II; HR; 1.17, 95% CI; 1.01-1.36, stage III + IV; HR; 1.65, 95% CI; 1.52-1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57-1.86).

Conclusion

This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC.     

Matrix metalloproteinases and their inhibitors and inducer in gestational trophoblastic diseases and normal placenta

Objectives

This study aimed to investigate the expression of recently identified matrix metalloproteinases (MMPs), their inhibitors (TIMPs), and inducer (CD147) in a wide range of gestational trophoblastic diseases (GTD) thereby expanding our understanding of the potential role of MMPs in GTD.

Methods

Paraffin sections of 10 normal first-trimester placentas (NP), 10 partial moles (PM), 10 complete moles (CM), 5 choriocarcinomas (CCA) and 5 placental site trophoblastic tumors (PSTT) were studied immunohistochemically for expression of MMP-7, MMP-14, MMP-21, MMP-28, TIMP-3, TIMP-4 and CD147. Immunolocalization of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13 and TIMP-1 was performed on 5 CCA and 5 PSTTs.

Results

CCA showed stronger intensity for MMP-14 and MMP-28 than PSTT (p < 0.05, p < 0.05). CCA and PSTT had stronger expression of MMP-21 than NP, PM and CM (p < 0.05, p < 0.05, p < 0.01). PSTT (p < 0.05, p < 0.05), NP (p < 0.01, p < 0.01) and CM (p < 0.01, p < 0.05) showed stronger staining for TIMP-3 and TIMP-4 than CCA.

Conclusion

Choriocarcinoma's high expression of MMPs and low expression of MMP inhibitors may contribute to its invasiveness and metastatic potential. Similarly, PSTT's lower expression of MMPs and high expression of MMP inhibitors may partly explain its lower invasiveness. Agents that inhibit MMP may prove useful in treating GTD.     

Correlation between overexpression of transforming growth factor-beta 1 in occluded fallopian tubes and postsurgical pregnancy among infertile women

Objective

To compare the expression profiles of transforming growth factor-beta 1 (TGF-β1) and its receptors in occluded tubes of infertile women with those of control patients and to evaluate the potential correlation with postsurgical pregnancy outcome.

Methods

The expression profiles of TGF-β1, TGF-β1R1, and TGF-β1R2 in occluded fallopian tubes were compared using immunohistochemistry between 60 infertile patients with adhered tubes and 60 control patients with normal tubes; potential correlations with postsurgical fertility were evaluated at 2-year follow up.

Results

Immunostainings of TGF-β1, TGF-β1R1, and TGF-β1R2 were all significantly elevated in patients with adhered tubes compared with normal specimens (P < 0.001). In adhered specimens, correlation analyses showed positive correlations between TGF-β1 and TGF-β1R1 (P = 0.008), and TGF-β1 and TGF-β1R2 (P = 0.035). At 2-year follow up, 32 of the 60 infertile women had achieved normal pregnancies, 5 had had ectopic pregnancies, and 23 remained infertile. Correlation analysis showed that TGF-β1 expression level was negatively correlated with pregnancy outcome (r = -0.445, P < 0.001), independent of adhesion severity or patient age.

Conclusion

TGF-β1 expression was independently correlated with the postsurgical pregnancy outcome among infertile women.     

Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: a Gynecologic Oncology Group study

Objective

Excision repair cross-complementation group 1 (ERCC1) is required for the repair of platinum-induced DNA damage. This study sought to assess the prognostic value of ERCC1 expression, measured by immunohistochemistry (IHC) using a highly specific antibody, in advanced epithelial ovarian cancer (EOC) patients treated with platinum-based chemotherapy.

Methods

Formalin-fixed, paraffin-embedded tumors were collected from two GOG phase III trials (GOG-172 and GOG-182) of patients with stage III/IV EOC treated with platinum-based chemotherapy. ERCC1 was detected by (IHC) using FL297 polyclonal antibody and tumors were categorized as negative or positive, based on nuclear staining of tumor cells. ERCC1 genotyping was performed as previously reported. Associations between ERCC1 expression and clinical characteristics, platinum responsiveness, progression-free survival (PFS) or overall survival (OS) were evaluated.

Results

Of 408 eligible patients, 27% had tumors that were ERCC1 positive. ERCC1 expression was not associated with clinical characteristics or platinum-responsiveness. Women with ERCC1-positive versus -negative tumors had similar median PFS (17.9 months versus 17.5 months, respectively, p = 0.59), median OS (52.0 months versus 47.0 months, respectively, p = 0.30), risk of disease progression (adjusted hazard ratio [HR] = 0.90, 95% confidence interval (CI): 0.71-1.15, p = 0.41), and risk of death (adjusted HR = 0.81, 95% CI: 0.61-1.07, p = 0.14). ERCC1 expression, as measured by IHC, was not associated with single nucleotide polymorphisms (SNPs), in codon 118 and C8092A, of the ERCC1 gene.

Conclusions

ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy.     

CYP1A1 polymorphism in adolescents with polycystic ovary syndrome

Objective

To evaluate the rates of the CYP1A1 Ile/Val polymorphism in Turkish adolescent females.

Methods

The CYP1A1 Ile/Val polymorphism was analyzed by collecting DNA samples from 44 adolescents with polycystic ovary syndrome (PCOS)—according to the Rotterdam criteria—and 120 healthy female controls aged 13-18 years in Ankara, Turkey.

Results

There was a 2.5-fold increase in the frequency of the CYP1A1 Ile/Val genotype in adolescents with PCOS compared with the control group (odds ratio [OR] 2.54; 95% confidence interval [CI], 1.143-5.637; P < 0.001), in addition to a 2.4-fold increase in the frequency of the Val allele (OR 2.43; 95% CI, 1.099-5.397; P < 0.001).

Conclusion

The data show an association between CYP1A1 and PCOS, indicating that variant alleles of the gene may affect the metabolic and transport pathway of estrogens, thus causing PCOS.     

20 year experience of postoperative radiotherapy in IB-IIA cervical cancer patients with intermediate risk factors: impact of treatment period and concurrent chemotherapy

Objective

To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors.

Methods

Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n = 56) or CCRT (n = 54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n = 39), RT 2000-2010 (n = 17) and CCRT 2000-2010 (n = 54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n = 48).

Results

Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p = 0.012) and distant metastasis (p = 0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p < 0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups.

Conclusions

This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.     

Endometrial leukemia inhibitory factor as a predictor of pregnancy after in vitro fertilization

Objective

To determine whether there is an association between endometrial expression of leukemia inhibitory factor (LIF) in the luteal phase of the menstrual cycle preceding in vitro fertilization (IVF) and treatment outcome.

Methods

Biopsy specimens from the endometria of 52 women in the luteal phase were immunostained against LIF. Embryo culture and transfer were done according to standard procedures.

Results

Clinical pregnancy occurred in 39% of the women following IVF, and strong endometrial immunohistochemical staining for LIF was associated with pregnancy (P = 0.01). The women with a strong LIF expression had a 6.4-fold higher chance of becoming pregnant than those with weaker intensities (P = 0.005).

Conclusion

Endometrial expression of LIF during the luteal phase can be used as a predictor of IVF success.