bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interval and non-compliant breast cancers diagnosed in women aged 50–69 in a Canadian breast cancer screening program: Clinical-pathologic correlations
Authors: Rayson D. , Abdolell M. , Payne J. , Foley T. J. , Younis T. , Barnes P. J. , MacIntosh R. F. , Caines J. 
Published: March 2020

21060 Background: Assessment of interval breast cancers and screening compliance are important parameters in the assessment of any comprehensive breast screening program. Clinical-pathologic examination of interval cancers may also be helpful in understanding differences between screen-detected and interval disease. The Nova Scotia Breast Screening Program (NSBSP) was founded in 1991 and, as of Jan 2007, 86,071 women aged 50–69 have entered the program, with 255,350 screening examinations completed. Methods: The Mammography Information System and Diagnostic Reporting System databases were used to identify all interval (diagnosed after a negative screen and before the recommended next screen) and non-compliant (diagnosed after a negative screen and after the recommended next screen) invasive breast cancer diagnoses. Unpaired t-tests were used to compare age at diagnosis, detection time and tumor size and the Chi- square test was used to compare the odds ratio of nodal involvement between interval and non-compliant cases. Results: A total of 1,189 screen-detected, 309 interval and 260 non-compliant invasive breast cancers were diagnosed amongst program participants aged 50–69 over this time period. Mean values (standard deviation, SD) for interval vs. non-compliant cases were; age at diagnosis 58.8 (SD=5.6) vs. 59.6 (SD=5.9) years (p=0.113); time to detection from last screen 363.9 (SD=187.6) vs. 1296 (SD=868.4) days (p<0.0001); tumor size 15.9 (SD=15.0) vs. 14.6 (SD=14.7) mms. (p=0.342). The incidence of nodal involvement in interval vs. non-compliant breast cancers was 32% and 23.5% respectively resulting in an odds ratio of 1.54, p=0.023. Conclusions: Interval and non-compliant breast cancers made up a significant proportion of all invasive cancers diagnosed amongst program participants. The finding of more cases having involved nodes at diagnosis despite no significant difference in mean age at diagnosis or tumor size suggests that interval disease may have a more aggressive phenotype. Data on tumor grade, lymphovascular invasion, hormone receptor status and HER2/neu over-expression are being collected. No significant financial relationships to disclose.
Expression of a cancer associated isoform of PCNA in breast cancer has implications as a potential biomarker
Authors: Malkas L. H. , Schnaper L. A. , Herbert B. , Abdel-Aziz W. , Liu Y. , Dobrolecki L. E. , Hoelz D. , Agarwal B. , Badve S. , Goulet R. J. , Hickey R. J. 
Published: March 2020

21069 Background: We have identified a novel cancer associated isoform of the protein, proliferating cell nuclear antigen (PCNA), termed (caPCNA), and demonstrated that this isoform arises through a direct protein post-translational modification, and not via genetic mutation or RNA splice variation. Our results suggest that caPCNA has the potential to serve as a highly effective and unique marker for identifying malignant breast cancer cells. Methods: This assertion is based on our proteomic-based analyses of more than 60 malignant and non- malignant breast cell lines and tissues. Commercially available antibodies against PCNA cannot distinguish between the different isoforms of PCNA present in malignant and non-malignant breast cells and cannot be used clinically to differentiate between normal and malignant breast tissue. However, we have recently developed a rabbit polyclonal antibody, (caPCNAab), which specifically recognizes only the caPCNA isoform expressed by malignant human breast cells. Results: Using this antibody we clearly show that caPCNA is expressed only in malignant breast cells and tissues, and can be found in early disease. caPCNA expression in tissues was quantified as average staining intensity X average percentage of cells stained. Using this criterion the following data were obtained: 10 cases of normal breast tissue (reduction mammoplasty) gave a total score of 1%; 35 cases of normal breast tissue adjacent to malignancy scored as 4%; 30 cases of DCIS scored as 90%; and 55 cases of invasive breast carcinoma scored as 120%. The five cases of ADH examined thus far were shown to score similar to that of normal breast tissue. Conclusions: The implication of these data is that the development of a caPCNAab-based IHC stain could potentially be used to reliably stain only in situ or invasive carcinoma, and distinguish genuinely benign lesions (e.g., ADH) from carcinoma, (e.g., DCIS) allowing definitive diagnosis in such cases where a limited amount of an atypical lesion prevents definitive diagnosis on routine H/E stained sections alone. For the patient population, this could result in a marked decrease in the need for either a repeat core biopsy or an excisional biopsy due to an inconclusive initial diagnosis. No significant financial relationships to disclose.
Epidermal Growth Factor Receptor (EGFr) status detection in correlation to objective response on cetuximab-based therapy in patients (pts) with advanced colorectal cancer (ACC)
Authors: Gevorgyan A. , Di Bartolomeo M. , Andreola S. , Orsenigo M. , Casieri P. , Signoroni S. , Cortinovis D. , Martinetti A. , Pilotti S. , Bajetta E. 
Published: March 2020

21070 Background: In current clinical practice Cetuximab represents a standard therapy for Irinotecan resistant pts with ACC, where EGFR-immunohistochemistry (IHC) evaluation is positive. In absence of reliable molecular predictors of the clinical benefit to anti-EGFR therapy, we have studied EGFR protein expression and gene status in order to correlate them to the clinical response. Methods: We investigated 40 primary colorectal carcinoma specimens. EGFR-protein expression was evaluated by Immunohistochemistry (IHC) using PharmDX-Kit DAKO Cytomation. IHC evaluation was performed using combined score based on the sum of percentage of positive cells and the staining of each sample. We identified three EGFR-score categories: 0–2, 3–5, 6–7 corresponding to low, intermediate and high expression respectively. EGFR-genetic status was conducted by Dual-Colour FISH (LSI EGFR-probe Vysis Inc).Gene and chromosome 7 copy numbers were identified by fluorescence in situ hybridization (FISH-LSI EGFR-Dual-colour-probe Vysis-Inc) as follows: tumor samples had a high EGFR-gene copy number if there was high polysomy ( 4-copies 40% of cells) or gene amplification (gene-clusters, gene/chromosome ratio per cell of 2, 15 copies of EGFR/ cell in 10% of cells) . The analysis of clinical data from all patients treated with Cetuximab (400–250mg/m2/w) and Irinotecan (300mg/m2/d1q21) was then performed. Results: EGFR-(IHC) high score was observed in 7pts from which only 2 had an objective response (OR). Intermediate (13pts) with 3 OR, low (12pts) with 1 OR and negative (8pts) with 2OR. Main FISH patterns were: high polisomy/amplification in 8pts with no response on cetuximab therapy. Low polisomy described in 19pts with 3 cases of disease remission. Disomy in 13pts with 5OR. No relationship was detected between IHC-score evaluation and FISH pattern. The clinical benefit (OR+stable disease =6months) was 65% in score-group 0–2; whereas 46% and 57% in groups 3–5/6–7 respectively, without statistical significance. Conclusion: According to our experience, IHC and FISH are unable to provide adequate selection criteria for the patients with different EGFR-status expression, who can benefit from Cetuximab therapy. No significant financial relationships to disclose.
SK3 polyglutamine tract polymorphism and acute oxaliplatin neurotoxicity: A translational study
Authors: Basso M. , Spada D. , Modoni A. , Cassano A. , Inno A. , Bagalà C. , Pozzo C. , Schinzari G. , Tonali P. A. , Barone C. 
Published: March 2020

21076 Background: Acute neurotoxicity of l-oxaliplatin (l-OHP), characterized by cold-induced paresthesias, muscle cramps and tightness, seems electrophysiologically related to an abnormal nerve hyperexcitability (NHE) resembling neuromyotonia, an autoimmune disease caused by autoantibodies directed against voltage-gated potassium channels (VGKC). This l-OHP-related channelopathy seems to be reversible, but there is no agreement about the channel involved, most investigators favouring voltage-gated sodium channels. SK3 VGKC are mainly located in the peripheral nervous system and are characterized by an highly polymorphic CAG motif. We hypothesized that SK3 potassium channel dysfunction might be responsible for nerve hyperexcitability in patients treated with l-OHP. Methods: Pts eligible for an l-OHP-containing regimen were enrolled. Detailed neurological examination, nerve conduction studies (NCS) and needle electromyography (EMG) were performed before and after l-OHP administration. Furthermore, a venous blood sample was obtained from each pt in order to perform genetic analysis. Genomic DNA was extracted from pts’ leukocytes and PCR-mediated amplification of the second polyglutamine CAG tract of SK3 gene was carried out; PCR products were analyzed on polyacrylamide gel stained with Ethidium Bromide. Results: We evaluated 20 pts (14M, 6F); mean age was 59 yrs. According to neurophysiologic data it was possible to divide pts into 3 groups: G0 (no symptoms or signs of NHE), 7 pts; G1 (cold induced paresthesias-mild NHE), 8 pts; G2 (muscle cramps-severe NHE), 5 pts. Genetic analysis showed different alleles ranging from 125 to 225 bp. In particular, 75% of pts carrying a 175 bp allele experienced severe acute toxicicy (G2 group), and 15% mild toxicity (G1 group). The 175 bp allele was found only in 1/7 G0 pts (15%); in these pts the alleles distribution was diffusely scattered. Conclusions: Acute and reversible NHE observed in some pts treated with l-OHP might be produced either by an increased sodium conductance or by a decreased activity of VGKC. The high percentage of the 175 bp allele, that we found in the G2 group, induces us to think that the polymorphism at CAG locus of SK3 may be responsible for l-OHP toxicity. Sequence analysis of PCR gene products is ongoing. No significant financial relationships to disclose.
The impact of DNA methylation on the identification of recurrent prostate cancer
Authors: Alumkal J. J. , Zhang Z. , Humphreys E. B. , Bennett C. , Mangold L. A. , Carducci M. A. , Partin A. W. , Garrett-Mayer E. , DeMarzo A. M. , Herman J. G. 
Published: March 2020

21086 Purpose: Biochemical (PSA) recurrence of prostate cancer following radical prostatectomy remains a major problem. Better biomarkers are needed to identify high and low-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the impact of changes in DNA methylation on biochemical recurrence in men with prostate cancer. Methods: We examined the methylation status of fifteen genes using MSP (Methylation Specific PCR) on tissue samples from 151 patients with clinically localized prostate cancer for whom at least five years of follow-up after prostatectomy was available. Results: In a multivariable logistic regression analysis, extra capsular penetration, high Gleason score, and involvement of the lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of recurrence. In addition, samples with methylation of 2 specific genes involved in cell-cell adhesion and apoptosis were associated with biochemical recurrence with an odds ratio of 5.64 (95% CI=1.47–21.7, p=0.012) compared to samples without methylation of both of these genes. The methylation status of these 2 genes had a higher sensitivity (72.3%; 95% CI=57–84.4%) for detecting recurrences than all the clinico-pathological variables (p<0.02) except extra-capsular penetration (p=0.346). The methylation status of these 2 genes had a similar negative predictive value (79.0%; 95% CI=66.8–88.3%) as the individual clinico-pathological variables examined. Conclusion: DNA Methylation of specific genes is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even one considers the prognostic clinico-pathologic variables used in the clinic today. Our findings should be validated on another larger group of patients with prostate cancer who have undergone radical prosatetectomies. No significant financial relationships to disclose.
Molecular analysis of the Epstein-Barr virus LMP1 in Hodgkin lymphoma from Argentina and Brazil: Identification of a distinct LMP1 deleted variant
Authors: Chabay P. , Hassan R. , Guiretti D. , Valva P. , Barros M. , Lorenzetti M. , De Matteo E. , Zalcberg I. , Rey G. , Preciado M. V. 
Published: March 2020

21099 Background: Epstein Barr virus (EBV), a human oncogenic virus, has two types, EBV1 and 2, and several polymorphic markers allow individual variants to be distinguished. Variations in EBV latent membrane protein 1 (LMP1) gene could define a more oncogenic strain or reflect geographic EBV origin. By sequence analysis of C-ter, N-ter and promoter (prom) regions, 4 distinct EBV groups (A to D) have been defined. Aim: To analyze LMP1 molecular variability of two different groups of Hodgkin`s lymphoma (HL) from the same geographic area. Methods: EBV association by EBERs in situ hibridization and LMP1 immunohistochemistry was analyzed in 27 HL from Argentina (Arg) and 36 HL from Brazil (Br). EBV type was assessed by EBNA PCR. C-ter LMP1 PCR was done in all cases. Sequencing of C-ter, N-ter and prom regions was done in 16 patients. Results: 21/27 (78%) Arg HL and 31/36 (86%) Br HL were EBV1, while 6/27 (22%) and 4/36 (11%) were EBV2, respectively (p= 0.29). Coinfection was observed in 1 (3%) Br HL. LMP1 deleted (del) variant was observed in 20/27 (74%) Arg HL and 20/36 (55%) Br HL (p= 0.18), as well as in non-neoplastic controls, 4/11 and 3/10 (36 and 30%) from Arg and Br respectively. Most LMP1 del displayed high number (5–7) of 33bp repeats (86% LMP1 del Br HL and 77% LMP1 del Arg HL) compared with LMP1 wt that exhibited low number (3–4) 33bp repeats (68% LMP1 wt Br HL and 100% LMP1 wt Arg HL). Analysis of LMP1 sequences showed that: LMP1 wt C-ter regions had unmutated N-ter and prom as B95.8, A and B groups (31%), except for a case showing new mutations. LMP1 del C-ter regions showed molecular identity with C group, but they showed new, undescribed mutations in prom and N-ter (63%). Conclusions: We found high frequency of LMP1 del variants in HL from Argentina and Brazil, which was associated with high number of 33bp repeats in C-ter region. This suggests a role for this variant in lymphomagenesis. A new molecular variant with characteristic promoter and N-ter mutations was identified in LMP1 del cases, which could be proposed as a regional South American variant. No significant financial relationships to disclose.
EGFR is frequently hyperexpressed in human malignant peripheral nerve sheath tumors (MPNST) and is preferentially localized in high grade areas
Authors: Emile J. , Tabone S. , Bahleda R. , Terrier P. , Bieche Y. , Beauchet A. , Terrier-Lacombe M. , Lemoine A. , Penault-Llorca F. , Le Cesne A. 
Published: March 2020

21105 Background: MPNST are highly malignant Schwann cell neoplasms that are generally resistant to conventional radiation and chemotherapy. Mouse models and in vitro data suggest that epidermal growth factor receptor (EGFR) expression is implicated in malignant transformation of Schwann cells. Methods: MPNST samples from 52 patients were studied for EGFR, Ki67, neurofibromin, p53 and survivin expression by immunohistochemistry and for EGFR amplification by in situ hybridization. Results were correlated with clinical data. EGFR RNA were also quantified by RT-PCR in 20 other MPNST and 14 cutaneous neurofibroma samples. Results: Half of the patients had a neurofibromatosis type 1 (NF1), and their age was lower at diagnosis (19 versus 27 years, P=0.04). EGFR expression was detected in 86% of MPNST, and was more frequent in NF1 (95% versus 75%). The staining of tumor cells was heterogeneous in several cases, and closely associated with high grade, Ki67 high and p53 positive areas. MPNST expressed a higher level of EGFR transcripts than neurofibromas. The five year survival was 33%, and NF1 status was the only prognostic factor in multivariate analysis. Conclusion: Our data suggest that EGFR may become a target for new therapies in MPNST, in particular in NF1-associated MPNSTs. No significant financial relationships to disclose.
Detection of ovarian cancer-specific gene by differentially expressed gene polymerase chain reaction prescreening and direct DNA sequencing
Authors: Kim J. , Pak J. H. , Choi W. H. , Kim J. Y. , Joo W. D. , Kim D. Y. , Suh D. S. , Kim Y. M. , Kim Y. T. , Nam J. H. 
Published: March 2020

21106 Background: To detect the genes differentially expressed in the ovarian cancer, we analysed the genes in the ovarian cancer and normal ovary by differentially expressed gene(DEG) PCR using the RNA extracted from the both tissues. We examined the relationship between the specific genes of ovarian cancer and pathogenesis of ovarian cancer. Methods: Differentially expressed genes were screened by ACP-based PCR. Differentially expressed bands were extracted from agarose gel, and then directly sequenced. Finally we determined the clinical importances of differentially expressed genes. Results: Some genes were overexpressed in the ovarian cancer tissue than normal ovary, such as plexin B1(PLXNB1), aminoacylase 1(ACY1), solute carrier family 25 protein(SLC25A5), triosephosphate isomerase 1(TPI 1), poliovirus receptor-related 3 protein(PVRL 3), clusterin, LY6/PLAUR domain containing 1 protein(LYPDC 1). And other five genes were more expressed in the normal ovary than ovarian cancer, such as ribosomal protein L11 and L23, tenascin XB (TNXB), complement component 1 and actin alpha 2. Conclusions: Clusterin was highly expressed in the tissue from ovarian cancer, which was identified with anti- or proapoptotic activity regulated by calcium homeostasis in prostate, breast and colorectal cancers. And it suggests the possibility that regulation of clusterin activity provides the prospect of breaking down cancer cells‘ resistance to apoptosis in the ovarian cancer. Ribosomal protein L11 and L23 was highly expressed in normal ovary, which plays an important role in regulating the stability and function of the p53 tumor suppressor protein. It suggests that suppression of ribosomal protein L11 may act an important role in proliferation of ovarian cancer and over-expression of ribosomal protein L11 may act an important role in cell cycle arrest in the treatment of the ovarian cancer. No significant financial relationships to disclose.
Topoisomerase II-alpha (TOP2A) gene co-amplification does not predict response to therapy and survival in Her-2 neu positive metastatic breast cancer
Authors: Kapoor A. , Chow S. , Bhargava R. , Surti U. , Rosenzweig M. , Vuga M. , Brufsky A. 
Published: March 2020

21108 Background: Preliminary data from a phase III trial of adjuvant traztuzumab (BCIRG, SABCS 2005, abstract 1045) suggested that co-amplification of the genes for HER2 and topisomerase II alpha (TOP2A) on chromosome 17 resulted in improved disease free survival with chemotherapy regimens containing both and anthracycline and traztuzumab. We sought to determine if co-amplification of HER2 and TOP2A was a predictor of response and benefit (or lack thereof) to herceptin containing chemotherapy in the metastatic setting, since few women receive both therapies concurrently for MBC. Methods: A tissue mircoarray (TMA) with 3-fold redundancy was constructed using 0.6mm cores from primary or metatstatic paraffin embedded tumor from 124 cases from Magee-Women's Hospital which were Her2 2+ or 3+ by IHC, or amplified by FISH, on pathology report. Four micron thick TMA sections were used for HER2 immunohistochemical (CB11 monoclonal antibody, Ventana Medical Systems, Tucson, AZ) and HER2 and TOP2A FISH analysis (HER2/CEP 17 and TOP2A/CEP 17 dual color probes from Vysis Inc. Downers Grove, IL). HER2 (or TOP2A) gene to chromosome 17 ratios of 2.0 or more was considered as amplification. Results: Tissue blocks from 52 tumors delivered clearly interpretable amplification for Her2 by FISH on reanalysis. The remaining 72 tumors are undergoing further reanalysis. Of the 52 tumors with Her2 amplification, 15 (29%) had co- amplification of TOP2A. Median survival was 44 months (95% CI, 31–69) for women with TOP2A coamplified tumors and 35 months (95% CI, 29- 63) for women with non-coamplified tumors (p=0.448, NS). Median time to progression on first therapy was 17 months (95% CI, 14–20) for women with TOP2A coamplified tumors and 15 months (95% CI, 12–17) for women with non-coamplified tumors (p=0.939, NS) Conclusions: In this analysis, TOP2A and HER2 gene co-amplification did not correlate with worse TTP on first metatstatic therapy or worse OS from metatstatic disease. No significant financial relationships to disclose.
Somatic mutations of EGFR and KRAS in pure bronchioloalveolar carcinomas and adenocarcinomas of the lung with bronchioloalveolar features
Authors: Dahabreh I. J. , Murray S. , Spiliadi H. T. , Karagiani E. A. , Stamatelopoulos A. , Vassilikos K. , Zanos G. , Janinis J. , Dahabreh J. 
Published: March 2020

21111 Background: EGFR mutations are more common in lung cancers from female, non-smoking patients of Asian ethnicity with adenocarcinoma histology. We investigated the relationship between clinicopathologic parameters and mutations of EGFR and KRAS in patients with pure bronchioloalveolar carcinomas (BACs) and adenocarcinomas (ADCs) with BAC features, not previously treated with EGFR inhibitors. Methods: We retrospectively reviewed the files of patients who were diagnosed with pure BACs or ADCs with BAC features between February 2001 and May 2005. Demographics, stage and smoking histories were recorded. Paraffin embedded tissue blocks were retrieved and re-examined using the WHO 1999/2004 histological criteria for lung cancers. EGFR expression, detected by immunohistochemistry, was scored from 0 to +3. Expression was considered positive when the score was +1, or higher. DNA was isolated from paraffin blocks (containing at least 75% tumor cell content) and exons 18–21 of the EGFR gene and exon 2 of the KRAS gene were amplified by PCR and bi-directionally sequenced. The chi-squared test and regression analysis were used to identify parameters correlating with EGFR or KRAS mutations. Results: A total of 46 patients were eligible for this study. Tissue was available from 43 patients, 19 with pure BAC and 24 with ADC with BAC features. There were 27 (62.8%) males and 16 (37.2%) females, all of Greek descent. Mean age was 62.7 years (range, 41–79). There were 34 smokers and former smokers (79%) and 9 never-smokers (21%). Tumors were classified as mucinous (20), non- mucinous (19) or mixed (4). We detected somatic EGFR mutations in 7 patients (including common mutations, delEx19, L858R, G719C), and KRAS codon 12 mutations in 13 patients. EGFR and KRAS mutations were mutually exclusive. No clinicopathologic parameters correlated with the presence of EGFR or KRAS mutations. Conclusions: Among Greek lung cancer patients with pure BACs or ADCs with BAC features, unselected for response to EGFR inhibitors, the incidence of KRAS or EGFR mutations was 30.2% and 16.3% respectively. EGFR and KRAS mutations were mutually exclusive but no clinicopathologic factor predicted the presence of mutations in either gene. Further molecular analysis is ongoing. No significant financial relationships to disclose.