bluuebunny/crossref_metadata_2025_split huggingface dataset:
High KI67 expression is associated, in a multi-variate model, with lower risk of biochemical recurrence in prostate cancer patients following radical prostatectomy
Authors: Gannon P. O. , Koumakpayi I. H. , Le Page C. , Alam Fahmy M. , Mes-Masson A. , Saad F. 
Published: March 2020

21112 Background: The prediction of disease progression in prostate cancer patients following radical prostatectomy (RP) remains problematic. The use of molecular markers could offer a better stratification of patients more at risk of progression. As such, we recently reported that nuclear ErbB3 was associated with Gleason score and hormone-refractory status. The objective of this study was to evaluate whether ErbB3 could predict overall biochemical recurrence (BCR). In addition, we evaluated if three nuclear markers known to be associated with progression (Cyclin D1, Ki67 and androgen receptor) were more significant predictors of BCR than ErbB3 alone or in combination. Methods: Using immunohistochemistry, we analyzed a tissue microarray containing 373 cores from 63 RP specimens. No patient had received hormone therapy prior to surgery and prior to BCR. The quantitative analysis of nuclear staining was measured by two independent observers (ErbB3, Cyclin D1 and AR) or with the ImagePro Plus softwareTM (Ki67). Marker expressions were categorized as either positive or negative according to the median expression. Results: Of the four markers analyzed, Ki67 alone was the strongest predictor of overall BCR. In a multi-variate Cox regression model (backward conditional), while controlling for the pre-operative PSA, Gleason score and lymph node invasion at time of surgery, KI67 was found to be an independent predictor of BCR with a KI67+ patients having lower risk of BCR (HR=-2.51, p=0.015, CI 95%: 1.19–5.29). We then analyzed if different marker combinations could predict BCR. Patients positive for nuclear AR or AR+/Cyclin D1+ double positive were found to have lower risk of BCR (Kaplan-Meier, p=0.047 and p=0.026, respectively). However, in the multi- variate model, the combinations of Cyclin D1+/AR+ (HR=-2.28, p=0.053, CI 95%: 0.94–5.49), ErbB3+/Ki67+ (HR=-2.43, p=0.034, CI 95%: 1.07- 5.52) and AR+/Ki67+ (HR=-2.32, p=0.049, CI 95%: 1.01–5.35) could not improve on the predictive value of KI67 alone. Conclusions: The major new finding of the study is that patients positive for KI67 expression were at a lower risk of developing BCR, which contrast previously published results, and warrants further investigations. No significant financial relationships to disclose.
Pattern of estrogen receptor positivity in breast cancer among the elderly
Authors: Cheung K. , Morgan D. A. , Wong A. W. , Parker H. , Ellis I. O. 
Published: March 2020

21122 Background: It is known that oestrogen receptor (ER) positivity in breast cancer increases with increasing age. Some clinical data show that radiotherapy can be safely avoided to achieve similar local control following lumpectomy in elderly patients taking tamoxifen; and that there is negligible benefit of adjuvant chemotherapy for patients approaching the age of 70. We postulate that biological differences (with ER being an important one) may be contributory. This study aimed to analyse the pattern of ER positivity in the elderly population. Methods: Among 2,061 patients >70 years who had operable primary breast cancer (<5cm) managed in a dedicated clinic from 1987, there were 1,557 tumours which had ER data available. Their pattern was studied and compared with that in 2,674 tumours from younger (= 70 years) counterparts treated during the same period in the same centre. Histochemical (H) score was measured using standard ER immunohistochemical assay and reported by the same team of dedicated breast pathologists. Results: The patterns of ER in different age groups are shown below. Conclusion: In all age groups there is a marked biphasal distribution of ER positivity, but in patients >70 years this biphasal distribution is more marked than in other age groups , with a great preponderance of highly ER-positive tumours, and a substantial minority being ER-negative (H=0), with very few in intermediate groups. Endocrine therapy is clearly appropriate for the highly ER-positive majority, but management of those ER-negative ones (H = 0) is a challenge. [Table: see text] No significant financial relationships to disclose.
Glutathione-S-transferase genes polymorphisms predict response and progression free survival in head and neck cancer patients treated with cisplatin based chemoradiotherapy
Authors: Federico M. H. , Brunialti K. C. , Castro G. , Pasini F. S. , Maistro S. , Mangone F. R. , Villar R. C. , Snitcovsky I. 
Published: March 2020

21127 Background: Alterations in the function of DNA repair genes and detoxification genes may influence response to cisplatin based chemoradiotherapy in patients (pts) with head and neck cancer. Our purpose was to evaluate the prognostic ability of polymorphisms of three genes glutathione S-transferase (GST), ERCC1 and XPD in patients with head and neck squamous cell carcinoma (HNSCC). Methods: A polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) or multiplex PCR approach was used to determine the frequency of the XPD Lys751Gln (n=29), ERCC1 Asn118 (n=50), GSTP1 Ile105Val (n=22) and GSTT1/GSTM1 (n=66), in DNA of peripheral lymphocytes. A total of 50 pts were treated with platinum based chemoradiotherapy exclusively and 16 pts received the same regimen in the adjuvant setting. Median follow-up was 6.4 months and 17 pts had tumor progression and 2 died, with a progression free survival (PFS) of 18 months. Results: The frequencies (%) of the distinct genotypes were, respectively, for the homozygous common allele and heterozygous plus homozygous polymorphic variant: 40 and 60 for ERCC1; 48 and 52 for XPD; 36 and 64 for GSTT/GSTM1, 41 and 59 for GSTP1. We did not observe any association between ERCC1, XPD, GSTM1/GSTT1 polymorphisms and response, but for GSTP1, the polymorphic variant was associated with tumor response, as compared to wild type (p=0.069 χ2 test). In relation to PFS, no associations were found between XPD, ERCC1 and GSTP1, however, for GSTM1/GSTT1, the null or heterozygous genotype (median survival: not reached, n=43) was associated with a better PFS, as compared to the wild type (18 months, n=23; p=0.087, Log-rank). Conclusions: Among the polymorphic variants studied here, our impression is that GST is the most powerful prognostic factor of favorable response and PFS to cisplatin based chemoradiotherapy in HNSCC. Supported by CAPES. No significant financial relationships to disclose.
Triple-negative phenotype is a strong predictor of sensitivity to epirubicin-cyclophosphamide (EC) then docetaxel (D) (ECD) primary chemotherapy (PCT) for localized breast cancer
Authors: Marty M. E. , Guinebretiere J. , Mathieu M. , Sigal-Zafrani B. , De Roquancourt A. , Spielmann M. , Giacchetti S. , De Cremoux P. , Spyratos F. , Asselain B. 
Published: March 2020

21128 Background: Molecular markers (GEP, p53 mutations,) could overcome usual predictors (size, pathology, Hormone receptors, HER2) in identifying patients (pts) experiencing complete pathological response (pCR) with anthracyclin based chemotherapy (Clin.Cancer Res., 2004, 10 6789). We aimed at validating and refining these finding in pts treated with ECD. Methods: From 05/2004 to 04/2006 170 pts not amenable to Breast Conserving Therapy and/or with high evolutive potential were randomly allocated to EC (75/750mg/sqm)x4 then D (100 mg/sqm)x 4 (with or without celecoxib in HER2-ve or trastuzumab (T) in HER2+ve. The primary endpoint - absence of residual invasive breast carcinoma and of nodal involvement (pCR)- was to be correlated with usual predictors , phenotype, GEP and p53 mutations assessed from core biopsies. pCR ranged from 13 to 14% in the arms without T thus without suggestion of a difference between these arms. pCR in the 30 HER2+ve pts having received ECD + T was 30% (NS). Results in 135 fully evaluable pts not allocated to T and having undergone secondary surgery are analyzed. Results: Main predictors and related pCR are shown in the table below Results of ongoing molecular analysis will be reported. Conclusions: Expression of ER appears to be the major prognosticator for ECD induced pCR. Triple negative breast cancers experience the highest pCR rate (p< 0.0001) (chi2 test with Yates correction). Molecular studies to be presented will show if GEP and/or p53 mutations could allow to improve such prediction. [Table: see text] No significant financial relationships to disclose.
Socioeconomic status as an independent prognostic factor in node negative, stage I-II breast cancer patients
Authors: Zeichner-Gancz I. , Munoz-Gonzalez D. E. , Pérez Sánchez V. M. , Castillero C. , Ramirez-Ugalde M. 
Published: March 2020

21129 Background: Many prognostic factors for breast cancer are known, of those, clinical , histological, genetical and the socioeconomic status are considered important for the outcome of these patients. The objective of our study vas to evaluate the Socioeconomic status as an independent factor for survival Methods: Clinical records of node negative clinical stage I- II patients treated at the institution from 1980 to 1996 were reviewed . We included those initially treated with surgery, available paraphine blocks, follow up of at five years (the ones that had no recurrence). They were divided in two groups: 1: Lower socioeconomic status, economically deprived and 2: medium low to high status. The slides were reviewed s and the blocks were processed for immuno-histochemistry: steroid receptors, Her-2, p 53 and CD 34. The analysis was performed with X2, , t test and log rank for difference in survival Results: A total of 81 patients were studied, 35 in group 1, and 46 in group 2. Mean age for groups 1 and 2 was of 52 (28–74) and 52.9 (28–83) years respectively (p=0.39). Were stage I in group 1 8, II-28. In Group 2 were stage I, 12, II-34 (p=0.87). Patients in both groups were treated with surgery alone, with radiotherapy, chemotherapy and/or hormone therapy, without statistical significance for treatment.Vascular or lymphatic permeation was observed in 20 and 22 patients from groups 1 and 2 respectively (p=0.40). Mean SBR was of 7.2 and 7.1 respectively for groups 1 and 2 (p=0.54) Estrogen receptor was present in 10 and 11 patients (p=0.63) and progesterone receptor in 8 and 6 (p0.25) for each group. Her-2 was over expressed in 12 and 17 patients from group 1 and 2, p53 in 6 and 14 respectively (p=0.17)and CD34 in 7 and 6 for both groups respectively ( p=0.40). Median survival was of 225 months for group 1 and not reached at 243 months for group 2, with 90.22% alive, p= 0.005 Conclusions: According to our results, in this group of well studied patients, the only significant factor observed that had an impact over survival was the socioeconomic status. None of the clinical, histological or genetical variables showed significance. We think that prospective studies with special emphasis on the socioeconomic status have to be carried out in order to try to explain the differences that we observed. No significant financial relationships to disclose.
The diagnostic value of serum levels of VEGF, bFGF and endostatin in patients with liver cancer
Authors: Nikopoulou A. , Makrantonakis P. , Karamouzis M. , Nikolaidis P. , Agorastos J. , Nikopoulos A. , Giannoulis E. 
Published: March 2020

21133 Background: : Aim of this study is to evaluate the diagnostic value of serum levels of vascular endothelial growth factor ( VEGF ), basic fibroblast growth factor ( bFGF ) and Endostatin in patients with primary hepatocellular carcinoma ( PHC ) and in patients with metastatic liver disease ( MLD ). Methods: Eighty participants were included in this study and divided into three groups. Exclusion criteria were history of myocardial infraction, stroke, diabetic retinopathy, rheumatoid arthritis, psoriatic arthritis, pregnancy, trauma and recent surgical treatment. In group A were included 20 normal controls (NC), in group B 30 patients with PHC and in group C 30 patients with MLD. The concentrations of VEGF, bFGF and Endostatin in serum were measured by using enzyme like immunosorbent assay kits (Quantikine R&D systems Inc., Mineapolis.MN). Results: Results are shown in table . In patients with PHC there was a positive correlation between the serum level of VEGF and tumor size (r=0.517, p=0.08), between the serum level of VEGF and platelets number (r=0.573, p=0.003) and between the serum level of VEGF and the serum level of a-fetoprotein (r=0.478, p=0.029). In patients with PHC sensitivity of VEGF, bFGF and Endostatin was found 60%, 54% and 23% respectively. In patients with MLD sensitivity of VEGF, bFGF and Endostatin was found 73%, 73% and 27.5% respectively. However, both in patients with PHC and with MLD specificity of VEGF, bFGF and Endostatin were found 95%, 95% and 100% respectively. Conclusions: Angiogenic factors VEGF, bFGF and Endostatin can distinguish normal controls from patients with liver cancer. Serum levels of VEGF are related to the size of the tumor in patients with PHC. Serum VEGF, bFGF and Endostatin could be useful tumor markers in the diagnosis of PHC and MLD because of their high specificity. The significant correlation of VEGF with a- fetoprotein indicates its importance as a marker in diagnosis of PHC. [Table: see text] No significant financial relationships to disclose.
Immature vessel percentage (IVP) as a potential predictive factor for anti-angiogenic therapeutics
Authors: Eid A. A. , Hennings L. , Caradine K. , Hodges A. , Safar A. M. 
Published: March 2020

21137 Background: As opposed to mature blood vessels, the early sprouts (lacking the pericyte coverage) are selectively obliterated after Vascular Endothelial Growth Factor (VEGF) antagonists (e.g. Bevacizumab BV). Microvessel density (MVD) has been widely used to assess tumor vasculature however; it does not give an indication of the degree of vessel maturity since it assesses endothelial cells irrespective to the pericyte coverage. With the introduction of BV for treatment of metastatic colon, lung and breast cancers, predictive markers to guide patient selection are desirable but lacking. Methods: To assess the maturity of tumor vascular beds we used double-labeling immunohistochemistry to colocalize endothelial cells (CD31+) and pericytes (aSMA+) in archived material from colorectal liver metastasis (n=13). None of these subjects received BV or chemotherapy prior to sampling. To represent various regions within a section, counts were performed in designated-low, and -high vascular regions. IVP, the main study endpoint, was estimated in both regions, and then averaged by two independent pathologists without particular training in angiogenesis. Results: There was a considerable degree of heterogeneity in the IVP within this group (SD 12.5, mean 26.6). However, the agreement between the 2 pathologists was relatively high with an intra-class correlation coefficient of 0.655. Conclusions: Considerable tumoral vascular heterogeneity exists in colorectal liver metastasis. IVP may predict therapeutic benefits from BV. In this era of anti-angiogenic therapy and in view of the toxicity and the financial burden of these agents, better patient selection using biologically relevant techniques such as the one described here need to be considered. IVP is a candidate tool with multiple advantages; it utilizes abundantly available material (subject to reconfirmation or testing in different settings), does not require particular training and appears reproducible. No significant financial relationships to disclose.
Prognostic and predictive value of vascular endothelial growth factor and soluble flt-1 and kdr levels in the sera of small cell lung cancer patients
Authors: Ustuner Z. , Saip P. , Yasasever V. , Ozturk B. , Vural B. , Ozbek U. , Topuz E. 
Published: March 2020

21152 Background: Small cell lung cancer (SCLC) has a rapid growth rate, and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre and post treatment serum VEGF and its receptors Flt-1 and Kdr levels in SCLC patients have impact on clinical outcome is unknown. Methods: From February 2001- January 2003, 39 consecutive patients (34 male, 5 female) with histologically proven SCLC were enrolled into the study. The patients were staged as limited and extensive according to the Veterans Administration Lung Group (VALSG). Pre treatment (n:39) and post treatment (n:25) serum samples of the same patients after 3 months of treatment were collected. The levels of VEGF and its receptors Flt-1 and kdr are measured in the serum by quantitative sandwich enzyme immunoassay technique. Statistical analysis was performed using the SPSS 10.0 pocket program. Results: The median pretreatment serum VEGF, Flt-1, and Kdr levels were 1,200 pg/ml (range, 1,414.3±956.2 pg/ml), 85 pg/ml (range, 97.8±70.7 pg/ml), and 11,550 pg/ml (range, 14,481±6,267 pg/ml) respectively. The pretreatment serum VEGF, Flt-1, and Kdr concentrations were not different in limited and extensive stages. We detected a poor but positive correlation between VEGF and Kdr (r=0.46, p=0.003). Pretreatment low serum VEGF value (<728.5 pg/ml) and good response to treatment were found as good prognostic factors in multivariate analysis. Surveillance of serum VEGF and Flt-1, Kdr values did not correlate with clinical parameters. Conclusions: Serum VEGF was found to be a significant and independent prognostic factor in SCLC patients. We showed a limited association between serum levels of VEGF and Kdr. Whether the levels of serum VEGF and its receptors Flt-1 and kdr have value in detecting treatment modalities of SCLC needs further studies. No significant financial relationships to disclose.
Bone morphogenic proteins 1 to 7 in human breast carcinoma
Authors: Davies S. R. , Watkins G. , Douglas-Jones A. , Mansel R. E. , Jiang W. G. 
Published: March 2020

21154 Background: Bone morphological proteins (BMPs) have a diverse role and they act in a time, concentration and cell type specific manner. They have been shown to regulate cellular motility and the cells ability to invade and recently BMP molecules have been shown to have an impact on the biological behaviour of breast cancer cells. In this study we looked, for the first time, at the expression of a panel of BMPs in breast carcinomas. Methods: Fresh frozen primary breast cancer tissues (n =120) and non-neoplastic mammary tissue (n = 32) were used. The distribution and location of BMPs was assessed using immunohistochemical methods and the levels of BMPs (BMP-1, -2, -3, -4, -5, -6, and -7) were determined using quantitative RT-PCR. The results were analysed against the clinical, pathological and follow-up (10 years) data. Results: BMP-2 and BMP-7 had a contrast pattern of expression in normal and tumour tissues, in that BMP-2 transcript level was lower and BMP-7 was higher in breast tumours than normal tissues. BMP-2 transcript was also significantly lower in tumours from patients with a moderate and poor prognosis than from those with a good prognosis (p=0.04). Also both BMP-2 and BMP-7 showed a significant difference between node positive and node negative tumours (p=0.033 and p=0.031 respectively). BMPs 1, 3, 4, 5 and 6 showed an inconsistent variation in transcript levels within the cancer subgroups with no statistically significant results. Conclusions: This study has demonstrated the differential expression pattern of BMP molecules in breast cancer and reveals a potential prognostic value of BMP-2 and BMP-7 for the patients. The findings may also suggest that these BMPs may be potential therapeutic targets. No significant financial relationships to disclose.
CXCR4/SDF-1 expression in early breast cancer (BC) is not influenced by circulating estrogens serum levels
Authors: Marini G. , Grisanti S. , Ruggeri G. , Ardighieri L. , Simoncini E. , Amoroso V. , Rangoni G. , Valcamonico F. , Lucini L. , Facchetti F. 
Published: March 2020

21159 Background: The chemokine SDF-1 and its receptor CXCR4 have been found to enhance the metastatic potential of BC cells and correlate with a poorer prognosis of BC patients. Estradiol is a known mitogenic factor for BC cells. SDF-1 has been reported to be an estradiol (E2)-inducible autocrine growth factor that supports the growth of breast cancer cell lines in vitro. The aim of this study was to verify whether estrogens serum levels may influence SDF-1 and CXCR4 expression in vivo, in a series of patients with early stage BC. Methods: 68 patients sequentially observed at the Spedali Civili di Brescia from 2001 to 2002, with a diagnosis of T1a,b,c, N0 breast cancer were retrospectively analysed. CXCR4 and SDF-1 expression was determined by immunohistochemistry with anti-human CXCR4 (Clone 44716) and anti-human SDF-1 (Clone 79018) monoclonal antibodies (R&D Systems, Minneapolis, USA) followed by incubation with the EnVision peroxidase kit (Dakocytomation, Glostrup, Denmark). A serum sample was obtained from all patients at baseline before surgery. Serum estrone (E1) and estradiol (E2) were measured by radioimmunoassay by using commercial kits (Alifax, Padua, IT and Ortho-Clinical Diagnostics, Amersham, UK, respectively). Results: Estrogens serum levels analysis revealed elevated levels of E1 in 9/54 (16%) post-menopausal patients, while E2 levels were in the normal ranges. SDF-1 was expressed in 68/68 (100%) patients with a diffuse and intense cytoplasmatic pattern of staining and CXCR4 was coexpressed in 15/68 (22%) patients with a predominant faint nuclear distibution (p 0,06). No significant correlations were found between CXCR4, SDF-1 and E1 or E2, respectively, as well as with other clinico-pathological characteristics. After a median follow-up of 48 months, 3/68 (4%) patients which all resulted CXC4/SDF1-positive, relapsed and are dead for metastatic disease. Conclusions: This study demonstrates that in T1N0 BC patients: 1) SDF-1 is high levels in the majority of cases; 2) CXCR4 is expressed in approximately 20% of cases with restriction to the nucleus and 3) serum levels of circulating E2 and E1 in pre- or post-menopausal patients, respectively, do not influence CXCR4/SDF-1 expression on breast cancer cells. No significant financial relationships to disclose.