bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial pro-gastrin-releasing peptide and neuron specific enolase in predicting radiological response and overall survival of patients with small-cell lung cancer
Authors: Ono A. , Naito T. , Tsuya A. , Nakamura Y. , Murakami H. , Kaira K. , Takahashi T. , Endo M. , Yamamoto N.
Published: August 2020

e22144

Background: Pro-gastrin-releasing peptide (ProGRP: P) and Neuron specific enolase (NSE: N) are specific serological markers in patients (pts) with small-cell lung cancer (SCLC). The aim of this study was to investigate whether decreasing of these tumor markers correlate with radiological response and prognosis in pts with SCLC. Methods: Out of 194 newly diagnosed SCLC pts from September 2002- April 2008 at our institution, we retrospectively reviewed consecutive 118 pts who had measurable lesions and elevated baseline levels of P and N before initial therapy (IT) including chemotherapy or chemoradiotherapy, and survived more than one month. P and N were measured on the first day of the every treatment course and after the final course of IT. Computed tomography (CT) was documented on baseline and every 2 courses of IT. Results: Forty-six (38.9%) pts had limited stage disease (LD) and 72 (61.0%) pts had extensive stage disease (ED). Both P and N levels at baseline were significantly correlated with the sum of longest diameter (SLD) in baseline CT; Spearman's ρ was 0.34 (P=0.001) and 0.44 (p<0.0001), respectively. Also, the decreasing rate of P and N correlated with the decreasing rate of SLD, ρ= 0.45 (p<0.0001) and 0.21 (p=0.03), respectively. Furthermore, the normalization of both P (<46pg/ml) and N (<10ng/ml) levels after 3 courses of IT was significantly associated with radiological response (p=0.015) including partial and complete response assessed by the Response Evaluation Criteria in Solid Tumors. In Cox's multivariate analysis, the normalization of both P and N levels after 3 courses of the IT (p=0.03, hazard ratio: 0.47, 95% CI 0.23–0.93) was significantly associated with prolonged survival, when adjusted by age, PS, and disease extent (LD or ED). Conclusion: Levels of P and N at baseline, and decreasing rate of P and N in IT were both associated with radiological response. In addition, the normalization of both P and N levels might be meaningful in predicting prognosis of SCLC pts.

No significant financial relationships to disclose.
Role of expression of FIP200 protein in progression of hepatocellular carcinoma
Authors: Ueda H.
Published: August 2020

e22147

Background: FIP200 protein is a newly identified protein, and recent report has shown that FIP200 interacts with p53 and inhibit progression and proliferation. Although expression of FIP200 has been confirmed in normal liver,the expression and function in human HCC is completely unknown. In this study, we examined expression of FIP200 in HCC cell lines and investigated the involvement of FIP200 in proliferation and apoptosis. We also examined expression of FIP200 using HCC tissues and the correlation between FIP200 expression and clinical outcome. Methods: The study was conducted using HCC cell lines (HepG2, HuH7, and Hep3B). P53 status in HepG2, HuH7 and Hep3B are wild type, mutant type and deficient types respectively. Expression of endogenous FIP200 was assessed by western blotting. To investigate antitumor function, we carried out BrdU incorporation assay with transfected FIP200. TUNEL was carried out for identification of apoptosis. We also reviewed 14 patients who had undergone initial liver resection for HCC. Immunohistochemistry analysis for FIP200 was performed and we investigated the FIP200 expression levels according to differentiation degree of HCC tissues. Results: Endogenous FIP200 was detected in all cell lines, and those expression levels were different among cell lines. Overexpression of FIP200 significantly decreased BrdU incorporation in HepG2 and HuH7 but not Hep3B. In the study of TUNEL, apoptosis was observed for p53 wild HepG2 transfected with FIP200. In Hep3B, there was no significant difference observed. As for clinical samples, FIP200 were detected in all HCC and non-HCC tissues. FIP200 expression levels in HCC tissues were decreased compared to non-HCC tissues. Furthermore, as differentiation degree poored, those expression levels were decreased in the same tissue as well as in the different tissue. Conclusions: Endogenous FIP200 was expressed in all cell line. Those expression levels were different according to p53 status. Our study demonstrated that FIP200 inhibit proliferation in HCC expressed p53, and induce apoptosis in p53 wild HCC but not p53 deficient HCC. Furthermore, the FIP200 expression levels were significantly associated with differentiation degree. These data suggest that FIP200 plays an important role in promoting tumor progression in HCC.

No significant financial relationships to disclose.
A genomic and transcriptomic approach to distinguish primary and metastatic ovary tumors
Authors: Meyniel J. , Cottu P. H. , Stern M. , Lebigot I. , Mignot L. , Roman-Roman S. , Sastre-Garau X.
Published: August 2020

e22150

Background: Distinction of primary ovarian tumors from metastatic tumors involving the ovary is in some cases challenging for final pathologic diagnosis and for treatment with efficient chemotherapy Methods: We gathered from our biobank 16 pairs of breast/ovarian tumors for some of which the diagnosis was uncertain. We investigated the possibility to improve diagnosis using genomic and transcriptomic tools. The pangenomic profiles of 16 pairs of primary breast carcinoma and ovary tumors (primary tumors or metastases from breast carcinoma) from the same patients were analyzed using the Affymetrix GeneChip Mapping 50K (XbaI) SNP arrays. The data were normalized with ITALICS algorithm. We analyzed the transcriptome of the paired samples using Affymetrix U133plus2 arrays. The data were normalized with GCRMA algorithm and a hierarchical clustering of these samples was performed, together with a dataset of primary and secondary ovary tumors. Results: Primary infiltrating lobular carcinoma (ILC) was observed in 6 patients, infiltrating ductal carcinoma (IDC) in 7 patients, 1 patient had one ILC and one IDC, 1 patient had a mixed IDC+ILC and 1 patient an undifferentiated cancer. All patients received adequate loco-regional and systemic therapies. Median time to diagnosis of ovarian tumor was 54 months. Ovarian tumors were considered as primary in 7 patients, and metastatic in 9 patients, and diagnosis was ambiguous in 4 of them. Four patients developed extra-abdominal metastases. Median survival from breast cancer diagnosis was 78 months, and from ovarian tumor diagnosis was 29 months. CGH array: In 12 pairs, the comparison of genomic profiles one with each other, confirmed the pathological characteristics of the tumors. In 4 cases, the genomic profiles established clearly the status of the ovary tumor whereas the pathological analysis did not. Transcriptome: The status established by the transcriptomic analysis was for each sample in total agreement with the status established by the genomic analysis. Conclusions: We clearly established in this training series that CGH array analysis could help to discriminate between primary and secondary ovarian tumors from breast cancer. Transcriptomic data confirmed these results. Further validation data are warranted.

No significant financial relationships to disclose.
Compliance and toxicity profiles of the CARISSA trial of postoperative cisplatin-based chemoradiation ± gefitinib in head and neck cancer
Authors: Thariat J. , de Raucourt D. , Giraud P. , Peyrade F. , Dassonville O. , Cosmidis A. , Dolivet G. , Calais G. , Santini J. , Bensadoun R.
Published: August 2020

e22152

Background: Concurrent cisplatin and postoperative irradiation (PORT) is the standard treatment for resected poor-risk squamous cell carcinoma of the head and neck (HNSCC) . However, a substantial number of patients fail to respond. Anti-EGFR agents, such as gefitinib, may improve outcomes and molecular markers might predict treatment efficacy. This was the basis for the CARISSA trial. There was some concern after hemorrhagic events occurred in a large independent trial of recurrent unresectable HNSCC. This caused a temporary interruption and safety profile analysis of CARISSA, which resumed after security reports showed no excess of hemorrhagic events. Methods: The CARISSA multicenter blinded randomized phase II trial compares PORT and cisplatin alone (arm A) or in combination with the EGFR Inhibitor ZD1839 gefitinib (arm B) in HNSCC and analyses EGFR-binding, gene polymorphisms, Western Blotting and immunohistochemistry. Patients are followed weekly. Toxicities are graded according to the NCI/CTCv.3 scale. Results: Thirty-eight patients have been included. Compliance to cisplatin was 56% in arm A and 44% in arm B (NS). Compliance to gefitinib was 60% with half cases interrupting treatment for toxicity. There were 18 and 20 grade (G) 3/4 non-hematological toxicities, 12 and 6 hematological G3/4 toxicities in arms A and B, respectively. Mucositis was the most common toxicity. G3 mucositis occurred in 4 and 5 cases in arms A and B, dermatitis in three cases in each arm and diarrhea in one case in each arm (NS). There were 7 cancer- related deaths and 3 of other causes. One tumor-bleeding event occurred in the arm without gefitinib. Full-dose radiotherapy was delivered in all but one case in each arm. Mean doses were 63.9 ± 1.9 (arm A) and 65.5 ± 0.9 Gy (arm B) or 64.7 ± 0.9 (arm A) and 65 ± 0.9 Gy (arm B) in groups where RT was uninterrupted or temporarily interrupted, respectively (NS). The two patients who did not receive full dose received 60 Gy. Conclusions: Compliance to PORT was similar with cisplatin alone or cisplatin + gefitinib. While there was no excess of hemorrhagic morbidity postoperatively (no gross disease), accrual continues with particular caution.

No significant financial relationships to disclose.
Clinical and pathologic correlation of p73 expression in surgically staged endometrial cancer
Authors: Resnick K. E. , Suarez A. , Nagel C. , Cohn D. , O'Malley D.
Published: August 2020

e22153

Background: p73 is a p53 homologue that has been implicated both as a tumor suppressor and oncogene. While known to play a role in the apoptotic response, homozygous p73 knockout mice have not shown an increased susceptibility to tumor formation. However, recent literature suggests that p73 dysregulation may play a role in retinoblastoma, ovarian and bladder cancer. We sought to correlate p73 status with clinical-pathologic factors including mismatch repair status, in a large cohort of comprehensively staged endometrial cancers. Methods: Primary endometrial and colon cancers were used to create a tissue microarray (TMA). Two-hundred eight endometrial specimens were available for evaluation. Immunohistochemistry with p73 was performed using commercial available antibodies. Positive staining was defined as > 10% cells having positive nuclear staining. Microsatellite (MSI) instability testing as well as IHC for p53 had been previously performed. Statistical analysis was performed using Fisher's exact test. Results: In six non-neoplastic control endometrial samples examined, p73 appears to stain mainly surface epithelial cell nuclei and superficial glands. p73 expression was identified in 71 (34%) of endometrial cancer specimens. There was no correlation between p73 status and histology, stage, grade or MSI status. Strong correlation that was noted between p53 status and p73 status. Ninety-eight (71%) of the 137 p73 negative tumors were noted to be wildtype(negative staining) for p53 (p<.001). However, when the (-)p73 (+)p53 and (+) p73 (+)p53 phenotypes were examined separately, there was no correlation with stage or grade. Conclusions: p73 is a p53 homologue with uncertain potential as an oncogene and tumor suppressor gene. To date, we offer the largest study of p73 expression in comprehensively staged endometrial cancer. While we show significant loss of p73 expression among cancer specimens, we were unable to demonstrate a relationship between p73 and clinical factors. However, an interesting correlation between p53 status and p73 does appear. The potential role for p73 and p53 in the apoptotic response to cytotoxic chemotherapy is interesting and deserves further study.

No significant financial relationships to disclose.
Circulating tumor cells in locally advanced breast cancer
Authors: García-Sáenz J. A. , Martín M. , Maestro M. , Vidaurreta M. , Veganzones S. , Rafael S. , Casado A. , Bobokova J. , Sastre J. , Arroyo M. , Diaz-Rubio E.
Published: August 2020

e22159

Background: A prospective study was conducted to determine the value of changes in circulating tumor cell (CTC) levels prior to and after the first cycle of neoadjuvant treatment in early prediction of pathologic response in locally advanced breast cancer (LABC). Methods: Two blood samples were obtained from 72 eligible LABC patients to isolate and enumerate CTCs before neoadjuvant chemotherapy started on day 1, and on day 21, immediately before second cycle administration. Results: Sixty patients (83.3%) had ≤1 CTC in the first sample and response rates in this cohort were: pathologic complete response (PCR) in 2 patients (5%); partial response (PR) in 35 (87.5%); stable disease (SD) in 2 (5%); progressive disease (PR) in 1 (2.5%). Twelve patients (16.7%) had ≥2 CTCs in the first sample; these patients were more likely to have triple negative tumors. All 12 had fewer CTCs in the second sample. Response rates in this second cohort of 12 patients were: PCR in 4 (34%); PR, 6 (50%); SD, 1 (8%); and PD, 1 (8%). pCR rate was markedly better in this second cohort (p<0.0042; OR 14.5, 95% CI 2.3–92). Conclusions: This study suggests that the presence of CTCs prior to neoadjuvant therapy might be a predictor of response to this therapy.

No significant financial relationships to disclose.
Immunohistochemical characteristics of breast cancer in Kazakh and Russian populations
Authors: Malyshev N. V. , Kulishov V. A. , Perminov V. S. , Sirota V. B.
Published: August 2020

e22162

Background: Ethnic differences of breast cancer were satisfactory investigated in different populations of the United States and some important findings were revealed. In other areas of the world amount of similar studies is relatively low. Our aim was to investigate the ethnical differences in the expression of standard immunohistochemical markers of breast cancer between two main nations of Kazakhstan and to reveal possible correlations between these markers and prognosis of the patients. Methods: 664 breast cancer patients, treated in Karaganda Regional Cancer Center during 2006–2007, were included in this study (222 patients of Kazakh population and 442 patients of Russian population). Immunohistochemical expression of estrogen and progesterone receptors (ER and PR) and Her2/neu was determined in all patients. Expression of steroid receptors was counted as positive if staining was presented in more than one percent of breast cancer cells. Her2/neu expression was divided in two groups: 0, 1+ - negative expression, 2+, 3+ - positive expression. The obtained data was calculated and processed by statistical program - Statistica 6.0. Results: Breast cancer in Kazakh patients demonstrated higher level of Her2/neu positive expression (31.5% versus 23.8, p<0.05) and lower level of isolated ER and PR expression (36.5 versus 44.3, p=0.05). Still, breast cancer in Russian patients was more frequently associated with basal phenotype (15.2 versus 9.5, p<0.05).Strong inverse correlation was observed between age of patients and Her2/neu status (p=0.0005) and direct correlation between age and positive expression of steroid receptors (p<0.05). These correlations were observed in both populations. Conclusions: Breast cancer in Kazakh population was statistically significantly associated with unfavorable prognostic and predictive immunohistochemical status, such as higher expression of Her2/neu and lower expression of steroid receptors. Nevertheless elder patients were more likely to have less aggressive disease, independently from population.

No significant financial relationships to disclose.
Lung cancer prediction: Phase transitions and cell ratio factors
Authors: Kshivets O.
Published: August 2020

e22170

Background: Search of precise prognostic factors for non-small lung cancer (LC) patients (LCP) was realized. Methods: In trial (1985–2008) the data of consecutive 490 LCP after complete resections R0 (age=56.7±8 years; m=439, f=51; tumor diameter: D=4.5±2.1 cm; pneumonectomies=206, lobectomies=284, combined procedures with resection of pericardium, atrium, aorta, VCS, carina, diaphragm, ribs=130; squamous=308, adenocarcinoma=147, large cell=35; T1=143, T2=217, T3=107, T4=23; N0=282, N1=115, N2=93; G1=114, G2=140, G3=236; early LC: LC till 2 cm in D with N0=58, invasive LC=432) was reviewed. Variables selected for 5-year survival (5YS) study were input levels of blood cell subpopulations, TNMG, D. Neural networks computing, Cox regression, clustering, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity. Results: For total of 490 LCP overall life span (LS) was 1824±1304 days (median=1879) and real 5YS reached 62%, 10 years - 50.3%, 20 years - 45.3%. 304 LCP (LS=2597.3±1037 days) lived more than 5 years without LC progressing. 186 LCP (LS=559.8±383.1 days) died because of LC during first 5 years after surgery. 5YS of early LCP was significantly superior (100%) compared with invasive LCP (56.9%) (P=0.000 by log-rank test). 5YS of LCP with N0 was significantly better (78.4%) compared with LCP with N1–2 (39.9%) (P=0.000). Cox modeling displayed that 5YS significantly depended on: phase transition (PT) in terms of synergetics “early-invasive LC”, PT N0-N12, histology, G1–3, cell ratio factors: ratio between the total populations of leucocytes, lymphocytes, neutrophils and LC cells (P=0.000–0.044). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT “early-invasive LC”, (rank=1), PT N0-N12 (2), histology (3), G1–3 (4), T1–4 (5), ratio of lymphocytes/LC cells (6), healthy cells/LC cells (7), erythrocytes/LC cells (8), thrombocytes/LC cells (9), eosinophils/LC cells (10), neutrophils/LC cells (11). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; urea under ROC curve=1.0). Conclusions: 5YS of LCP after radical procedures depended on: 1) PT “early-invasive LC”; 2) PT N0-N12; 3) cell ratio factors; 4) LC characteristics.

No significant financial relationships to disclose.
Chemokine receptor CXCR4 expression and its regulation in gastric cancer cells
Authors: Lee H. , Kim H. , Kim S. , Yun H. , Kim S. , Jo D.
Published: August 2020

e22173

Background: The chemokine receptor CXCR4 is associated with the biological behavior in several kinds of cancer, but few studies have addressed the expression and regulation of CXCR4 in gastric cancer. Methods: Five gastric cancer cell lines were studied. The expression of CXCR4 was investigated using RT-PCR, Westerning blotting, flow cytometry, and immunofluorescence staining. The regulation of CXCR4 expression by hypoxia, dexamethasone, and the proinflammatory cytokines was evaluated. Results: CXCR4 mRNA and proteins were detectable by RT-PCR and Western blot analysis, respectively, in all five cell lines. However, MKN-28, MKN-45, MKN-74, and SNU 16 cells did not express membrane CXCR4, but had abundant CXCR4 in their cytoplasm, as determined by flow cytometry and immunofluorescence staining. In contrast, a small population of KATO III cells expressed membrane CXCR4. Hypoxia up-regulated CXCR4 proteins and enhanced membrane expression of CXCR4 in human gastric cancer KATO III cells, which constitutively expressed membrane CXCR4 in a steady state, as revealed by Western blotting and flow cytometry, respectively. This hypoxia-induced expression of CXCR4 was mediated via hypoxia-inducible factor (HIF)-1α. In addition, KATO III cells exposed to hypoxia demonstrated enhanced migration in response to stromal cell-derived factor (SDF)-1α, a specific ligand for CXCR4. However, MKN-28, MKN-45, MKN-74, and SNU-16 cells, which lack membrane CXCR4 in a steady state, showed no change in CXCR4 expression in hypoxic condition. Treatment with IFN-γ, TGF-β, TNF-α, and dexamethasone did not induce any change in CXCR4 expression in all five gastric cancer cells. Conclusions: This study suggests that hypoxia up-regulates the membrane expression of functional CXCR4 via HIF-1α in human gastric cancer cells that basally express membrane CXCR4 in a steady state in vitro.

No significant financial relationships to disclose.
Comorbidity prior to diagnosis in patients with common cancer diagnoses
Authors: Olsson H. , Attner B. , Noreen D. , Lithman T.
Published: August 2020

e22180

Background: Chronic disease as diabetes, hypertonia and anemia may be associated with cancer risk as well as affect the short term survival of the malignancy. Methods: Using population based registry data from specialist and primary care in our health care region comorbidity in the form of anemia, hypertonia, diabetes, rheumatoid arthritis, chronic obstructive pulmonary diasease (KOL), and alcohol related diseases for patients with colon-, rectal-, lung-, prostate and breast cancer and survival were studied. Altogether 2047 colon cancer cases, 985 rectal cancer cases, 2017 lung cancer cases, 3578 breast cancer cases and 5106 prostate cancer cases diagnosed 2000–2005 were included. Results: were age and sex adjusted and one year survival was calculated. Comorbidity was studied prior to cancer diagnosis and in order to compare with the general population all first comorbidity diagnoses within 90 days were censored. Results The prevalence of the chronic diseases in the general population was for all ages diabetes 3.2%, rheumatoid arthritis 0.5%, hypertonia 6.8%, anemia 1.1%, KOL 1.0% and alcohol related diagnoses 0.7%. Patients with colon and rectal cancer had a higher prevalence of anemia, and diabetes. Patients with lung cancer had a higher prevalence of anemia, KOL, diabetes, rheumatoid arthritis for both men and women and for men also a higher prevalence of alcohol related diseases. Except for alcohol related diseases in females with breast cancer comorbidity for the above diseases was not significantly elevated for breast or prostate cancer. For all diagnoses hypertonia was significantly lower than in the general population. Survival of the different cancer diagnoses was not significantly related to the comorbidity except for a tendency of worse survival for patients with alcohol related disease. Conclusions: The prevalence of some common chronic diseases are elevated especially in colon-, rectal and lung cancer patients. The comorbidity does not seem to affect short term survival of the cancer patient except for alcohol related diagnoses. Our study also indicates the necessity to have all levels of care included in the study base of comorbidity and also emphasizes the need to censor time prior to diagnosis when comparing data with the general population.

No significant financial relationships to disclose.
Characteristics of bone mineral density at the time of diagnosis in postmenopausal breast cancer patients
Authors: Kim H. J. , Park E. , Lim W. , Sei J. , Koh B. , Son B. , Ahn S.
Published: August 2020

e22187

Background: Bone mass has been proposed as a marker of cumulative exposure to estrogen in women. We have studied the association between bone mass and breast cancer in postmenopausal women. Methods: We investigated the association between bone mineral density(BMD), as measured at the lumbar spine and femoral neck and the breast cancer in women age 50 or older, who were received an initial diagnosis of stage 0-III breast cancer, confirmed by pathologic assessment of breast tissue. We recruited 718 women with newly diagnosed breast cancer in a Asan Medical Center from 1, Jun. 2006 to 31, Dec. 2007. BMD was measured by lunar EXPERT-XL for breast cancer patients Results: Median age at diagnosis was 58 (range 47–82). Patients with higher BMD at lumbar spine were found to have low grade disease (p<0.005). The patients with hormone receptor positive breast tumor showed higher BMD at lumbar spine and lower serum 25(OH)D than hormone receptor negative tumor. Serum estradiol level did not show a relation to BMD. There were no significant differences between breast cancer stage and serum 25(OH)D and BMD. Conclusions: The patients who have hormone receptor positive breast cancer had higher Lumbar spine BMD and lower 25(OH)D than hormone receptor negative patients.

No significant financial relationships to disclose.
Contribution of BRCA1 and BRCA2 mutations to breast cancer in Tunisia
Authors: Wafa T.
Published: August 2020

e22191

Background: Hereditary breast cancer accounts for 3–8% of all breast cancers. It was recently estimated that a combination of BRCA1 and BRCA2 genes mutations is responsible for 30% of hereditary breast cancer cases. Methods: To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, 36 patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. Thirty three patients are suggestive of BRCA1 mutation and 3 are suggestive of BRCA2 mutation. Results: Four mutations in BRCA1 gene were described among which, one novel splice site mutation (330 dupA) and 3 frameshift mutations including the 4160 delAG, the 2789 delG and the 5385 insC. Our study is the first to describe the 5385 insC mutation which was described only among Jewish Ashkenazi population. Two frameshift mutations (1537 del4 and 5909 insA) were screened in BRCA2 gene. Nineteen percent (7/36) of the familial cases were altered on BRCA1 or BRCA2 genes with deleterious mutations at heterozygous state and 55% (20/36) by mutation with uncertain value (UV) or by single nucleotide polymorphisms (SNPs). Conclusions: Almost all the cases mutated by deleterious mutations on BRCA1 gene reported a family history of breast and/or ovarian cancer in the index case or in their relatives. On the contrary, patients with an UV mutation or SNPs have no history of ovarian cancer in their corresponding families. Our data are the first to contribute to information on mutation spectrum of BRCA genes and offer a recommended screening mode for clinical genetic testing policy in Tunisia.

No significant financial relationships to disclose.
The correlation among tissue, serum adiponectin levels and histopathological variables in gastric cancer patients
Authors: Bilici A. , Guler D. O. , Seker M. , Ustaalioglu B. O. , Sonmez B. , Karaduman M. , Oncel M. , Gumus M. , Salepci T. , Yaylaci M.
Published: August 2020

e22199

Background: Adiponectin is a new peptide hormone secreted from the adipose tissue, affecting the proliferation and insulin sensitivity in different cell types.The previous studies showed that the serum levels of adiponectin are decreased in patients with endometrial and breast cancer.In our study, demographic features and histopathological variables and the relationship among adiponectin levels of serum and gastric tissue were analyzed in gastric cancer patients. Methods: Thirty-five consecutive patients with gastric cancer included in this study.The serum levels of glucose, insulin, c-peptide, HbA1c, lipids and adiponectin were measured in patients.In addition, normal and tumor tissue levels of adiponectin were also detected.We analyzed the correlation among these parameters and patients demographic features, such as age, gender, body mass index (BMI) and histopathological variables. Results: Patients characteristics included 24 males (68.5%), 11 females (31.5%); median age was 64 (range:41–85). The mean serum, normal and tumor tissue levels of adiponectin were 49.4±0.8, 48.2±4.2, 48.6±2.9 ng/ml, respectively. There was no relationship among serum, normal and tumor tissue adiponectin levels (p>0.05).There was inverse correlation between the normal tissue levels of adiponectin and insulin (p=0.002).The serum adiponectin levels were significantly associated with tumor localization (p=0.03).However, there was inverse correlation between serum adiponectin levels and perineural invasion (p=0.02).In subgroup analysis, the serum, normal and tumor tissue levels of adiponectin in woman were not different compared with those in male patients (p>0.05).No relations were detected among tumor stage, grade, nodal status, lymphatic and vascular invasion, the other insulin-resistant status parameters and the levels of serum, normal and tumor tissue adiponectin (p>0.05). Conclusions: Our results suggest that no correlations among the levels of serum adiponectin,normal tissue and tumor tissue adiponectin levels,patients demographic features and histopathological variables except for the association of serum adiponectin with tumor localization and perineural invasion detected in gastric cancer patients.

No significant financial relationships to disclose.
Clinical and pathological features of breast cancer in Arab compared to Jewish women in Northern Israel
Authors: Zidan J. , Geslikov M.
Published: August 2020

e22201

Background: Breast cancer (BC) is the most common malignancy in both Jewish and Arab women in Israel. Although the incidence of BC is lower in Arab women it is diagnosed in younger age and seems to have worse prognosis. Recent data have suggested considerable molecular differences in BC from various ethnical groups. Molecular features are increasingly used for predicting cancer prognosis and response to treatment. The purpose of this study to compare clinical, pathological and molecular characteristics of BC in Arab and Jewish women in the Upper Galilee Methods: The files of 481 patients (pts) with breast cancer (BC) treated at the Oncology Institute, Ziv Medical Center between 2001 and 2007 were reviewed retrospectively. Type of breast operation and both clinical and all pathological findings of patients were summarized and correlated to the ethnicity of women. Results: Of the total 481 pts 380 were Jewish and 100 were Arab women. The main age at diagnosis was 49,4 years for Arabs and 59,5 years for Jews (p<0,01). At diagnosis 3% of Arab pts had DCIS compared to 7,4% in Jewish pts, stage I in 19% and 49,9%, stage II in 36% and 31,7%, stage III in 33,3% and 7,6%, stage IV in 9% and 3,7% of Arab and Jewish pts respectively (p<0,05). Well differentiated, moderately and poorly differentiated in 12%, 59% and 29% compared with 43,9%, 41,4% and 12,5% in Arabs versus Jews. Estrogen receptor was 69% in Arabs and 79% in Jews. HER-2 overexpression evaluated by IHC and CISH was diagnosed in 39% of Arab pts and in 24% Jewish pts (p<0,05). Lumpectomy was done in 36% in Arabs versus 64% in Jews (p<0,05). Conclusions: Our data demonstrate younger age and more advanced tumor at diagnosis in Arab compared to Jewish women. All pathological and molecular figures were more aggressive in Arab compared to Jewish women in Israel. Mammography for screening may be started at age 40 years in Arab women and treatment could be more aggressive.

No significant financial relationships to disclose.
Expression of angiogenic genes in resectable non-small cell lung cancer (NSCLC)
Authors: Cabrera A. , Jantus Lewintre E. , Sirera R. , Honguero A. , Gil M. , Blasco A. , Sanmartin E. , Arnau A. , Guijarro R. , Camps C.
Published: August 2020

e22207

Background: NSCLC is a major cause of cancer-related death worldwide. The prognosis for lung cancer patients is poor with 5-years survival rates being less than 15%. It is known that angiogenesis is an essential event for solid tumour growth. Vascular endothelial growth factor (VEGF) family of ligand and receptors (VEGFR) are described as powerful angiogenic factors. VEGF belongs to a protein family, within which Placental growth factor (PlGF) is a member, they bound to their receptors at the membrane levels, gathering a cascade of intracellular events. In this study, we examine the expression of angiogenic genes in NSCLC samples correlating the expression of these genes between them and with clinicopathological variables. Methods: We performed real-time quantitative polymerase chain reaction (RT-qPCR) to assess the expression of VEGF, PlGF, VEGFR1 and VEGFR2 in frozen lung cancer specimens from untreated NSCLC patients who had undergone surgical resection (n=21). For this purpose, RNA was extracted and RTqPCR was performed using TaqMan® probes. Relative quantification was calculated by Pfaffl formulae, using an endogenous gene for normalization. We correlate the expression of the angiogenic genes between them and with other biologic variables. Statistical analysis were done using the SPSS 13.0 software. Results: Our results show that tumor samples have higher expression of PlGF than normal tissue. The expression of PlGF and VEGF correlates with the expression of their receptors in the group of samples analyzed. The expression of VEGFR1 and VEGFR2 was also significant correlated. We found a significant correlation between the levels of expression of PlGF and the tumor size (p= 0.023, Spearman's test), whereas no relation was found between the expression of the genes and the histology or stage of disease. Conclusions: Our results reveal that, in NSCLC, PlGF mRNA is higher in tumor than in normal tissue and is positively correlated with the tumor size and with the expression of angiogenic receptors. Theses finding could indicate that PlGF have some role in lung cancer progression and may be a promising new biomarker in NSCLC, but still more investigations are necessary with a larger number of samples. Supported by Instituto de Salud Carlos III (Fondo de Investigación Sanitario Grant).

No significant financial relationships to disclose.
Apoptotic genes as a prognostic factor in penile epidermoid carcinoma
Authors: Novais P. C. , Paula A. A. , Rodrigues A. A. , Barione D. F. , Peria F. M. , Tirapelli D. P. , Tucci S. , Cologna A. J. , Martins A. C. , Tirapelli L. F.
Published: August 2020

e22208

Background: The penile cancer is a rare condition in European men. The treatment can cause physiological and/or psychological problems in patients. The comprehension of the disease behavior can provides new, non-invasive therapeutic interventions. For this reason, the protein expression of apoptotic genes (caspase-3, caspase-8, bcl-2) were analysed with the immunohistochemistry technique, correlating with tumor grade (I, II and III) and with the patient survival in order to understand the basic mechanism of tumoral transformation. It is beyond doubt that studies related with penile cancer and its mechanism of apoptosis is scarce in the literature. Therefore, this study can contribute with information about this disease. Methods: The immunohistochemistry reactions on 50 samples of squamous cell carcinoma were carried out with the avidina-biotina-imunoperoxidase method with antigen recovery. The analyses were made using the graduation method ‘in crosses‘ (0 to 4 crosses - no stain to more than 75% of positives cells) and in categories (low, intermediate, high) of the cytoplasm immunoreactivity of the epidermoide penile carcinoma cells. Results: It was observed a statistically significant difference when the expression of caspase-3 were compared with the grades I and II of the tumor (p=0.0010) and when comparing the patient survival with the grades I and II of the tumor (p=0.0212). The protein expression of caspase-3 and caspase-8 was lesser in relation to bcl-2, suggesting that the apoptotics rate in this carcinoma is low. The higher expression of the anti-apoptotic protein bcl-2 suggests a higher preservation of the tumoral cells. Conclusions: The analysis did not showed correlation between the proteins expression with the survival curve of patients.

No significant financial relationships to disclose.
Circulating tumor DNA in plasma of breast cancer patients from India
Authors: Bhattacharyya S. , Raina V. , Shukla N. K. , Shukla S. , Kumar R. , Hedau S. , Kumar G. , Bharti A. C. , Rath G. K. , Das B. C.
Published: August 2020

e22213

Background: Recently, breast cancer has become the most common cancer among women in all urban population in India. Annually about 80000 new cases and 40000 deaths occur and majority of breast cancers are pre-menopausal. Conventional diagnostic methods are not very sensitive especially in early stages of cancer. This necessitated a more sensitive and reliable method for early diagnosis leading to effective treatment, better prognosis and survival. Recently, the level of cell free circulating tumor DNA in blood plasma or serum of patients with variety of tumors are being considered as reliable non-invasive diagnostic tool but no study has been done in India. The present study has therefore been undertaken to evaluate clinical utility of cell free DNA as potential biomarkers for early diagnosis and management of breast cancer. Methods: 25 newly diagnosed untreated breast cancer patients and 25 healthy subjects having no sign of significant medical illness with informed consent were enrolled for the study. 9 patients after chemotherapy were also included in the study. Blood plasma collected from both patients and controls were employed for DNA isolation, using Qiagen kit. Concentration of cell free plasma DNA was analyzed by 3 methods viz. nanodrop spectro-photometry, integrated density value (IDV) of PCR products of Exon 7 of p53 gene and quantitative real time PCR (cycles threshold converted to genome equivalent). All values of DNA concentration obtained by three methods used as continuous variables and receiver operating characteristic (ROC) were plotted and the cut-of value was determined at 90% sensitivity and 100% specificity level of ROC. Results: Mean free plasma DNA concentration as determined by both Q-RT PCR and IDV in cancer patients was found to be significantly higher in advanced stage breast cancer patients than in controls (genome equivalent 18850 vs 431; IDV 17912 vs 4197; p=0.001). However, no significant difference could be observed in early stage disease as compared to controls possibly due small sample size. Conclusions: Free Plasma DNA concentration is a reliable molecular marker for detection of breast cancer and can serve as a prognostic indicator leading to its potential clinical application either alone or in combination with other conventional methods.

No significant financial relationships to disclose.
Triple negative breast cancer: An institutional review
Authors: Dioca M. , Savignano M. , Gimenez L. , Marino L. , Delfino C. , Alvarez A. M. , Mickiewicz E.
Published: August 2020

e22214

Background: Triple negative breast cancer (BC) is a distinct group of tumors that show common but heterogeneous morphologic, genetic, and immunophenotypic features. Despite differences in the definition and prevalence, it comprises 8% to 20% of all breast cancers and is associated with an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up (particularly in the first 5 years).We study the pathological characteristics and the clinical outcome of a cohort of 77 triple negative BC patients (pts) diagnosed at our Institution. Methods: Between January 1999 and September 2008, 77 (stage I to III) triple negative BC pts. were retrospectively analyzed. All pts had their receptor status, Her neu, ck-5, ck-6 and staining for EGFR by the same pathologist. Pathological parameters (Pp) analyzed were: status of axilary lymph nodes (LN), nuclear grade, histologic grade, mitotic index and vascular invasion and the use of antraciclins in the adjuvant setting. Univariate and multivariate analysis (proporcional hazard regression Cox model) for the Pp associated with relapse, and the log rank test to compare two curves of each Pp for disease free survival (DFS), and overall survival (OS) were performed. Results: The median age was 57.8 years (range 30–86 years).The median follow up time was 57.7 months (range, 4- 241). From 77 Pts. analized, 65 (84.4%) were basal-like and 43 (64.6%) of those were GH3. Stage at the time of presentation was: 16 (20,7%) stage I; 40 (51,9%) stage II; 21 (27,7%) stage III. Pre-menopausal status was 29,48% (23 pts.), and 61% (47 pts) were LN negative. Overall, relapse rate was 38.5 % (n= 30), 63 Pts (81.8%) are still alive. Median DFS was not reached. Global DFS and OS were 59% and 79% respectively, and status of LN was the only prognostic factor. LN- vs LN+ DFS (p< 00.02) and OS p (< 0.02).All others Pp analyzed were not statistically significative. Conclusions: Despite previous studies have demonstrated that triple negative is an independent marker of poor prognosis in BC as a whole, in the LN-negative, and LN-positive groups, in this basal like population only positive LN was an independent poor prognostic factor for DFS and OS.

No significant financial relationships to disclose.
CDH-1 germ line mutations in diffuse gastric and infiltrating ductal breast cancer
Authors: Efremidis A. P. , Fostira F. , Panopoulos C. , Papademitriou K. , Pistalmazian N. , Tsoukalas N. , Yannoukakos D.
Published: August 2020

e22218

Background: Hereditary Diffuse Gastric Cancer (HDGC) syndrome is characterized by the predisposition to gastric cancer of the diffuse type and to breast cancer of the lobular type. The autosomal dominantly inherited germline mutations of the E- cadherin (CDH1) gene are the defects underlying the HDGC syndrome. The median age of onset for diffuse gastric cancer is 38 years. CDH1 mutations are highly penetrant, conferring a cumulative risk of diffuse gastric cancer of 75%. Methods: Genomic DNA was purified from peripheral blood leukocytes following standard chloroform extraction. The complete coding sequences of the CDH1-gene, including splice junctions, were amplified by Polymerase Chain Reaction (PCR) and electrophorized in an ABI Prism 310 Genetic Analyzer. Results: A pathogenic mutation located on exon 7 of the CDH1 gene was identified in a female patient diagnosed with bilateral breast cancer at the age of 36. She underwent bilateral mastectomy for an infiltrating ductal adenocarcinoma of the left breast and in situ lobular of the right breast. At the age of 45 the patient underwent gastrectomy for diffuse type gastric adenocarcinoma. She had a positive family history for breast and gastric cancer from both sides, but without meeting the absolute clinical criteria for hereditary diffuse gastric cancer syndrome. The nonsense mutation found was probably maternally inherited, since the maternal grandmother was diagnosed with breast cancer at the age of 38. Conclusions: The selection process of patients for genetic testing for the HDGC syndrome is not quite clear at the moment, as it is apparent that more types of breast cancer and not only lobular, can be associated with the syndrome. Criteria should be more flexible in respects to the histopathology of the cancer type. This is the first CDH1 mutation identified in a Greek patient.

No significant financial relationships to disclose.
Biomarkers in cancer: Survey of diagnostic needs
Authors: Holzman T. , Gibbons W.
Published: August 2020

e22222

Background: Much ongoing work in the field of diagnostics is related to identifying novel and clinically useful tumor markers. However, it is not clear that this discovery is focused on the clinical uses that are most important to physicians. Methods: Consequently, we conducted a survey to assess these needs. Our survey of oncologists, specialists and primary care physicians received 236 responses. Of these, 214 doctors provided their view, ranking with an 8 point Likert scale, for which of eight aspects of cancer that they would like to better differentially diagnose. Of the respondents, 45% were oncologists, 17% primary care, 16% urology and 15% OB/Gyn. Of the physicians surveyed, 57% were in private practice and 32% were in academic medicine, with the remaining 11% in a variety of other settings. Results: As may be unexpected, respondents believed that they still could benefit most from diagnosis itself (indexed score 6.1), followed closely by improving earlier diagnosis or identifying latent disease (5.6), as opposed to simple screening (4.82). The aspects that they believed required the least improvement were prognosis for metastasis (3.6) and prognosis for progression (4.0). Surprisingly, desire for the ability for better treatment planning was unremarkable as well (4.3). We also gauged the respondents familiarity with tumor markers using a 5 point Likert scale. 29% considered themselves very familiar, and only 13% considered themselves with less than average familiarity. Conclusions: The results of the survey suggest it may be useful to consider evaluation of biomarkers which aid early diagnosis rather than disease prognosis.

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Important serum markers in malignant lymphoma
Authors: Yavuz S. , Erkisi M. , Petekkaya I. , Basel N.
Published: August 2020

e22225

Background: In this study, 78 patients with new diagnosed, 21 patients with relapsed malignant lymphoma who applied to Cukurova University Hospital between March 2006 - 2008, and 36 age and sex matched healthy control group were evaluated and have been followed up. Methods: The aim of this study was to investigate if; any acute phase reactants or lymphocyte markers in peripheral blood have any predictive role concerning the treatment response, or disease progression. Results: Peripheral blood CD20 (+) lymphocyte levels were slightly higher in new diagnosed patients (12.09±13.79), than the control group (11.25 ±4. 79) but, much lower in relapsed patients (7.30±9.51, P= 0.038). After the chemotherapy (CT), CD20 (+) cell percentage decreased significantly only in new diagnosed patients (p<0.001). Pretreatment CD20 (+) cell levels were higher in responding patients than no responders (15. 42 ± 13.30 versus, 6.72 ± 5.24 p= 0.052). Peripheral blood CD 4 (+) cell levels were below the healthy control group (p= 0.01) and remained low after the CT. Interestingly, CD8 (+) cell levels increased in responders, after the CT (p= 0.046) in both patient groups. CD 56(+) lymphocyte levels were higher only in new diagnosed patients than healthy group (p= 0.05). Its level increased further after the CT (p= 0.044). Serum TNF α levels were higher in patient groups than control (p<0.001). Its level decreased following CT (p= 0.002). CRP levels were higher in both patient groups and remained high following the CT (p<0.001), regardless of the response status. Ferritin levels were also higher in patients groups (p<0.001). Pre-treatment serum ferritin levels were lower in responders, than no responders (236.65 ± 242.17 ng/ml versus 718.77 ± 645.24 ng/ml, p= 0.02). Serum prealbumine levels were lower in lymphoma patients than the healthy controls (p< 0.001). Its level was increased after treatment, especially in patients with recurrent disease (21.15± 5.89 versus 26.60 ± 7.29 mg/dl, p= 0.019). Conclusions: In conclusion, it was decided that; during the different stages of lymphoma progression, several mutations may occur, in the different components of the host immune system. Some of the immune responses would continue in spite of complete clinical remission, as some others would predict the response.

No significant financial relationships to disclose.