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  • 1
    Language: English
    In: BMC cancer, 2012-03-21, Vol.12 (1), p.99-99
    Description: The treatment of patients with malignant brain tumors remains a major oncological problem. The median survival of patients with glioblastoma multiforme (GBM), the most malignant type, is only 15 months after initial diagnosis and even less after tumor recurrence. Improvements of standard treatment including surgery and radio-chemotherapy have not lead to major improvements. Therefore, alternative therapeutics such as oncolytic viruses that specifically target and destroy cancer cells are under investigation. Preclinical data of oncolytic parvovirus H-1 (H-1PV) infection of glioma cells demonstrated strong cytotoxic and oncosuppressing effects, leading to a phase I/IIa trial of H-1PV in patients with recurrent GBM (ParvOryx01). ParvOryx01 is the first trial with a replication competent oncolytic virus in Germany. ParvOryx01 is an open, non-controlled, two groups, intra-group dose escalation, single center, phase I/IIa trial. 18 patients with recurrent GBM will be treated in 2 groups of 9 patients each. Treatment group 1 will first receive H-1PV by intratumoral injection and second by administration into the walls of the tumor cavity during tumor resection. In treatment group 2 the virus will initially be injected intravenously and afterwards, identical to group 1, into the surrounding brain tissue during tumor removal. Main eligibility criteria are: age of 18 years, unifocal recurrent GBM, amenable to complete or subtotal resection. Dose escalation will be based on the Continual Reassessment Method. The primary objective of the trial is local and systemic safety and tolerability and to determine the maximum tolerated dose (MTD). Secondary objectives are proof of concept (PoC) and Progression-free Survival (PFS) up to 6 months. This is the first trial with H-1PV in patients with recurrent GBM. The risks for the participants appear well predictable and justified. Furthermore, ParvOryx01 will be the first assessment of combined intratumoral and intravenous application of an oncolytic virus. Due to its study design the trial will not only generate data on the local effect of H-1PV but it will also investigate the penetration of H-1PV into the tumor after systemic delivery and obtain safety data from systemic delivery possibly supporting clinical trials with H-1PV in other, non-CNS malignancies. ClinicalTrials.gov Identifier: NCT01301430.
    Subject(s): Recurrence ; Genetic Vectors - administration & dosage ; Humans ; Brain Neoplasms - pathology ; Clinical Protocols ; Male ; Oncolytic Viruses - genetics ; Disease Progression ; H-1 parvovirus - genetics ; Oncolytic Virotherapy ; Glioblastoma - therapy ; Administration, Intravenous ; Injections, Intralesional ; Glioblastoma - pathology ; Brain Neoplasms - therapy ; Female ; Complications and side effects ; Chemotherapy ; Patient outcomes ; Research ; Drug therapy ; Health aspects ; Glioblastoma multiforme ; Parvovirus infections ; Risk factors ; Cancer ; Index Medicus ; Study Protocol
    ISSN: 1471-2407
    E-ISSN: 1471-2407
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Cancer immunology and immunotherapy, 2009, Vol.58 (10), p.1535-1544
    Description: This review summarizes studies on humoral immune responses against tumor-associated antigens (TAAs) with a focus on antibody frequencies and the potential diagnostic, prognostic, and etiologic relevance of antibodies against TAAs. We performed a systematic literature search in Medline and identified 3,619 articles on humoral immune responses and TAAs. In 145 studies, meeting the inclusion criteria, humoral immune responses in cancer patients have been analyzed against over 100 different TAAs. The most frequently analyzed antigens were p53, MUC1, NY-ESO-1, c-myc, survivin, p62, cyclin B1, and Her2/neu. Antibodies against these TAAs were detected in 0-69% (median 14%) of analyzed tumor patients. Antibody frequencies were generally very low in healthy individuals, with the exception of few TAAs, especially MUC1. For several TAAs, including p53, Her2/neu, and NY-ESO-1, higher antibody frequencies were reported when tumors expressed the respective TAA. Antibodies against MUC1 were associated with a favorable prognosis while antibodies against p53 were associated with poor disease outcome. These data suggest different functional roles of endogenous antibodies against TAAs. Although data on prediagnostic antibody levels are scarce and antibody frequencies for most TAAs are at levels precluding use in diagnostic assays for cancer early detection, there is some promising data on achieving higher sensitivity for cancer detection using panels of TAAs.
    Subject(s): Biological and medical sciences ; Medical sciences ; Antineoplastic agents ; Immunotherapy ; Pharmacology. Drug treatments ; Animals ; Antigens, Neoplasm - immunology ; Neoplasms - immunology ; Antibodies, Neoplasm - blood ; Autoantibodies - blood ; Humans ; Neoplasm Proteins - immunology ; Antibody Formation ; Autoimmunity ; Autoantibodies ; Immune response ; Analysis ; Tumor antigens ; Oncology, Experimental ; Mucins ; Diagnosis ; Research ; Tumor proteins ; Cancer ; Index Medicus ; Humoral immune response ; cancer ; tumor antigens ; autoantibodies
    ISSN: 0340-7004
    E-ISSN: 1432-0851
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: International journal of cancer, 2018-07-01, Vol.143 (1), p.139-150
    Description: Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR‐deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR‐deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR‐deficient cells by chemoprevention or vaccines against MMR deficiency‐induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. What's new? Whether mutations in mismatch repair (MMR) genes play an initiating or a secondary role in colorectal carcinogenesis in Lynch syndrome is unclear. To better understand the pathogenic process, the authors of this study developed a Lynch syndrome model delineating three molecular pathways of colorectal cancer formation. Some colorectal cancers were found to grow from MMR‐proficient adenomas after secondary inactivation of the MMR system. However, most colorectal cancers developed from MMR‐deficient precursor lesions, either via an adenomatous phase or as nonpolypous lesions. The findings underline the importance of prevention measures targeting MMR‐deficient cells in the clinical management of Lynch syndrome.
    Subject(s): microsatellite instability ; colorectal cancer ; mismatch repair deficiency ; Lynch syndrome ; Adenomatous Polyposis Coli Protein - genetics ; Genetic Predisposition to Disease - genetics ; Adenoma - genetics ; Proto-Oncogene Proteins p21(ras) - genetics ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Humans ; DNA Repair Enzymes - genetics ; Male ; Sequence Analysis, DNA ; Tumor Suppressor Protein p53 - genetics ; beta Catenin - genetics ; DNA Mismatch Repair ; Female ; High-Throughput Nucleotide Sequencing ; Models, Genetic ; Mutation ; Immunohistochemistry ; Medical research ; Gene mutations ; Analysis ; Colorectal cancer ; Medicine, Experimental ; Models ; Tumor proteins ; Carcinogenesis
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
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  • 4
    Language: English
    In: Cancer research (Chicago, Ill.), 2011, Vol.71 (17), p.5670-5677
    Description: Analysis of tumor-infiltrating lymphocytes (TIL) in primary human colorectal cancer (CRC) by in situ immunohistochemical staining supports the hypothesis that the adaptive immune response influences the course of human CRC. Specifically, high densities of TILs in the primary tumor are associated with good prognosis independent of other prognostic markers. However, the prognostic role of TILs in metastatic CRC lesions is unknown, as is their role in response or resistance to conventional chemotherapy. We analyzed the association of TIL densities at the invasive margin of CRC liver metastases with response to chemotherapy and progression-free survival in a set of 101 large section samples. High-resolution automated microscopy on complete tissue sections was used to objectively generate cell densities for CD3, CD8, granzyme B, or FOXP3 positive immune cells. A predictive scoring system using TIL densities was developed in a training set and tested successfully in an independent validation set. TIL densities at the invasive margin of liver metastases allowed the prediction of response to chemotherapy with a sensitivity of 79% and specificity of 100%. The association of high density values with longer progression-free survival under chemotherapy was statistically significant. Overall, these findings extend the impact of the local immune response on the clinical course from the primary tumor also to metastatic lesions. Because detailed quantification of TILs in metastatic lesions revealed a strong association with chemotherapy efficacy and prognosis, we suggest that the developed scoring system may be used as a predictive tool for response to chemotherapy in metastatic CRC.
    Subject(s): Gastroenterology. Liver. Pancreas. Abdomen ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Pharmacology. Drug treatments ; Biological and medical sciences ; Medical sciences ; Antineoplastic agents ; Tumors ; Disease-Free Survival ; Neoplasm Metastasis ; Prognosis ; Lymphocytes, Tumor-Infiltrating - pathology ; Cell Count ; Colorectal Neoplasms - drug therapy ; Humans ; Colorectal Neoplasms - pathology ; Liver Neoplasms - secondary ; Index Medicus
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: HighWire Press (Free Journals)
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Journal of investigative dermatology, 2012-02, Vol.132 (2), p.491-493
    Subject(s): Tumors of the skin and soft tissue. Premalignant lesions ; Biological and medical sciences ; Medical sciences ; Dermatology ; Microsatellite Instability ; Skin Neoplasms - etiology ; DNA Mismatch Repair ; Humans ; Skin Neoplasms - genetics ; Index Medicus
    ISSN: 0022-202X
    E-ISSN: 1523-1747
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Article
    Article
    2007
    ISSN: 0278-0240 
    Language: English
    In: Disease markers, 2007, Vol.23 (4), p.315-330
    Description: In industrialized countries, population wide cytological screening programs using the Pap test have led to a substantial reduction of the incidence of cervical cancer. Despite this evident success, screening programs that rely on Pap-stained cytological samples have several limitations. First, a number of equivocal or mildly abnormal test results require costly work up by either repeated retesting or direct colposcopy and biopsy, since a certain percentage of high grade lesions that require immediate treatment hide among these unclear test results. This work up of mildly abnormal or equivocal cytological tests consumes a large amount of the overall costs spent for cervical cancer screening. Improved triage of these samples might substantially reduce the costs. Cervical cancer is induced by persistent infections with oncogenic human papilloma viruses (HPV). While HPV infection is an indispensable factor, it is not sufficient to cause cancer. The majority of acute HPV infections induce low grade precursor lesions that are cleared spontaneously after several months in more than 90% of cases, and less than 10% eventually progress to high grade lesions or invasive cancer. Progression is characterized by the deregulated expression of the viral oncogenes E6 and E7 in infected basal and parabasal cells. Novel biomarkers that allow monitoring these essential molecular events in histological or cytological specimens are likely to improve the detection of lesions that have a high risk of progression in both primary screening and triage settings. In this review, we will discuss potential biomarkers for cervical cancer screening with a focus on the level of clinical evidence that supports their application as novel markers in refined cervical cancer screening programs.
    Subject(s): Cell Proliferation ; Uterine Cervical Neoplasms - diagnosis ; Neoplasm Invasiveness ; Epigenesis, Genetic ; Humans ; Cervical Intraepithelial Neoplasia - diagnosis ; Vaginal Smears ; Papillomaviridae - isolation & purification ; Uterine Cervical Neoplasms - genetics ; Biomarkers, Tumor ; Mass Screening - methods ; Papillomaviridae - genetics ; Cervical Intraepithelial Neoplasia - virology ; Papillomaviridae - pathogenicity ; Chromosome Aberrations ; Genes, Viral ; Biomarkers ; Uterine Cervical Neoplasms - virology ; Female ; Cervical Intraepithelial Neoplasia - genetics ; Chromosomal Instability ; Oncogenes ; Index Medicus ; screening ; biomarker ; p16INK4a ; Cervical cancer ; HGCIN ; Other ; HPV
    ISSN: 0278-0240
    E-ISSN: 1875-8630
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Journal of clinical oncology, 2012-12-10, Vol.30 (35), p.4409-4415
    Description: Purpose Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6. Patients and Methods Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex-and MMR gene-specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk. Results The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers. Conclusion The sex-and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome. J Clin Oncol 30: 4409-4415. (C) 2012 by American Society of Clinical Oncology
    Subject(s): Gastroenterology. Liver. Pancreas. Abdomen ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Biological and medical sciences ; Medical sciences ; Tumors ; MutL Protein Homolog 1 ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Humans ; Middle Aged ; Netherlands - epidemiology ; Risk Factors ; Male ; MutS Homolog 2 Protein - genetics ; DNA-Binding Proteins - genetics ; Germany - epidemiology ; Neoplasms - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - epidemiology ; Adaptor Proteins, Signal Transducing - genetics ; Adult ; Female ; Registries ; Aged ; Retrospective Studies ; Mutation ; Nuclear Proteins - genetics ; Neoplasms - epidemiology ; Cohort Studies ; Index Medicus
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: International journal of cancer, 2013-10-01, Vol.133 (7), p.1624-1630
    Description: The differentiation between hereditary and sporadic microsatellite‐unstable (MSI‐H) colorectal cancer is a crucial step in Lynch syndrome diagnostics. Within MSI‐H colorectal cancers, the BRAF V600E mutation is strongly associated with sporadic origin. Here, we asked whether BRAF V600E‐specific immunohistochemistry (clone VE1) is helpful in separating sporadic from Lynch syndrome‐associated MSI‐H colorectal cancers. To that end, we performed VE1 immunohistochemistry and BRAF sequencing in a series of 91 MSI‐H colorectal cancer specimens from patients tested for Lynch syndrome. Concordance of VE1 immunohistochemistry and molecular BRAF mutation status was observed in 90 of 91 (98.9%) MSI‐H samples. All 11 tumors classified as BRAF V600E mutation‐positive by Sanger sequencing were immunopositive, and 79 (98.8%) of 80 tumors classified as BRAF wild type showed negative staining. All VE1‐positive tumors were MLH1‐ and PMS2‐negative by immunohistochemistry. None of the tumors from mismatch repair (MMR) gene germline mutation carriers (n = 28) displayed positive VE1 staining, indicating that BRAF V600E mutation‐specific immunostaining has a low risk of excluding Lynch syndrome patients from germline mutation analysis. In conclusion, implementation of VE1 immunohistochemistry was able to detect BRAF‐mutated MSI‐H colorectal cancers with a sensitivity of 100% and a specificity of 98.8%. Among MLH1‐negative colorectal cancers, the rate of VE1‐positive lesions was 21%, offering the exclusion of these patients from MMR germline testing. Therefore, we suggest the integration of VE1 immunohistochemistry into the diagnostic panel of Lynch syndrome. What's new? Lynch syndrome is one of the most frequent hereditary tumor syndromes. But its hallmark feature, high‐level microsatellite instability (MSI‐H), which is caused by genetic defects in the germline, also occurs in sporadic colorectal cancers, complicating its diagnosis. Here, BRAF V600E mutation‐specific immunohistochemical staining, which targets BRAF mutations found exclusively in sporadic colorectal cancer, is reported to successfully distinguish between hereditary and sporadic MSI‐H‐associated disease. Implementation of the antibody could facilitate diagnosis of the hereditary form while avoiding unnecessary cost‐intensive germline mutation analysis in sporadic cases.
    Subject(s): BRAF V600E ; microsatellite instability ; colorectal cancer ; hereditary nonpolyposis colorectal cancer ; Lynch syndrome ; Gastroenterology. Liver. Pancreas. Abdomen ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Biological and medical sciences ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Medical sciences ; Tumors ; Immunohistochemistry ; MutL Protein Homolog 1 ; Promoter Regions, Genetic ; Microsatellite Instability ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Humans ; Middle Aged ; Male ; Nuclear Proteins - metabolism ; Sequence Analysis, DNA ; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis ; Proto-Oncogene Proteins B-raf - genetics ; Base Sequence ; DNA Mismatch Repair ; Adaptor Proteins, Signal Transducing - genetics ; Aged, 80 and over ; Germ-Line Mutation ; Adult ; Female ; Aged ; Adaptor Proteins, Signal Transducing - metabolism ; Nuclear Proteins - genetics ; Gene mutations ; Analysis ; Colorectal cancer ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: International journal of cancer, 2012-01-15, Vol.130 (2), p.388-394
    Description: Diffuse overexpression of p16INK4a in basal and parabasal cells of cervical epithelium is a hallmark of human papillomavirus‐mediated transformation. Focal p16INK4a expression is occasionally observed in nondysplastic epithelium. In normal cells, expression of p16INK4a triggers cell cycle arrest. However, cells undergoing transformation in intraepithelial lesions actively proliferate. To prove that the different expression patterns of p16INK4a, i.e., focal versus diffuse, reflect biologically different entities, we hypothesized that p16INK4a‐positive cells in epithelia displaying focal p16INK4a expression pattern do not coexpress proliferation‐associated Ki‐67 protein, while p16INK4a‐positive cells in lesions with diffuse p16INK4a expression may do. A total of 138 cervical cone biopsies were stained for the expression of p16INK4a and Ki‐67 using a primary antibody cocktail. All metaplastic lesions (n = 21) displayed focal staining for p16INK4a, and in all of these lesions p16INK4a‐positive cells were found to be negative for Ki‐67 expression. Diffuse expression of p16INK4a was observed in 12/21 (57.1%) cervical intraepithelial neoplasia (CIN) 1 lesions, all of them simultaneously showed Ki‐67 immunoreactivity in a large proportion of p16INK4a‐positive cells. Seventeen of 23 (73.9%) CIN2 lesions and all 27 (100%) CIN3/carcinoma in situ (CIS) as well as all 46 (100%) carcinoma cases displayed diffuse and combined expression of p16INK4a and Ki‐67. Coexpression of Ki‐67 and p16INK4a in the same cell is entirely restricted to cervical lesions displaying diffuse p16INK4a expression, whereas in lesions with focal p16INK4a expression, p16INK4a‐expressing cells are negative for Ki‐67. Thus, diffuse expression of p16INK4a reflects lesions with proliferation‐competent cells, while p16INK4a‐expressing cells associated with focal expression patterns are cell cycle arrested.
    Subject(s): Ki‐67 ; transformation ; p16INK4a ; cervical intraepithelial neoplasia ; HPV ; Gynecology. Andrology. Obstetrics ; Biological and medical sciences ; Medical sciences ; Tumors ; Female genital diseases ; Biopsy - methods ; Cervical Intraepithelial Neoplasia - pathology ; Cervix Uteri - metabolism ; Humans ; Uterine Cervical Neoplasms - pathology ; Paraffin Embedding ; Metaplasia ; Uterine Cervical Neoplasms - metabolism ; Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis ; Cervical Intraepithelial Neoplasia - metabolism ; Cervix Uteri - pathology ; Female ; Ki-67 Antigen - biosynthesis ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: International journal of cancer, 2019-04-01, Vol.144 (7), p.1697-1703
    Description: Perioperative systemic treatment is standard of care for Caucasian patients with locally advanced, resectable gastric adenocarcinoma. The prognostic relevance of the microsatellite instability (MSI) status in patients undergoing neoadjuvant chemotherapy followed by resection is unclear. We analyzed the association of the MSI status with histological regression and clinical outcome in patients undergoing neoadjuvant systemic treatment. Tumor tissue from patients undergoing neoadjuvant chemotherapy followed by resection for gastric or gastroesophageal‐junction adenocarcinoma was analyzed for MSI status using a mononucleotide marker panel encompassing the markers BAT25, BAT26, and CAT25. Histological regression, relapse‐free survival and overall survival were calculated and correlated with MSI status. We identified the MSI‐H phenotype in 9 (8.9%) out of 101 analyzed tumors. Though a poor histological response was observed in eight out of nine MSI‐H patients, overall survival was significantly better for patients with MSI‐H compared to MSS tumors (median overall survival not reached vs. 38.6 months, log‐rank test p = 0.014). Among MSI‐H patients, an unexpected long‐term survival after relapse was observed. Our data indicate that the MSI‐H phenotype is a favorable prognostic marker in gastric cancer patients undergoing neoadjuvant treatment. The benefit of perioperative cytotoxic treatment in patients with MSI‐H gastric cancer, however, remains questionable. Future trials should stratify patients according to their MSI status, and novel treatment modalities focusing on MSI‐H tumors should be considered. What's new? Recent classification of gastric cancer into four molecular subtypes has paved the way toward better patient stratification for therapy. However, to date, the prognostic impact of microsatellite instability (MSI) status in patients with gastric and gastroesophageal junction adenocarcinoma undergoing neoadjuvant systemic therapy remains unclear. Our study shows that despite a poor histological response, clinical outcome among patients with high‐level MSI (MSI‐H) tumors is significantly superior in comparison to patients with microsatellite‐stable (MSS) tumors. The findings suggest that MSI‐H phenotype is a prognostic marker in gastric cancer patients undergoing neoadjuvant treatment, and that future studies should stratify patients according to their MSI status.
    Subject(s): microsatellite instability ; MSI ; neoadjuvant ; gastric cancer ; GE‐junction cancer ; chemotherapy ; Microsatellite Instability ; Adenocarcinoma - pathology ; Prognosis ; Humans ; Middle Aged ; Male ; Stomach Neoplasms - pathology ; Biomarkers, Tumor ; Esophageal Neoplasms - pathology ; Aged, 80 and over ; Adult ; Female ; Neoadjuvant Therapy ; Adenocarcinoma - genetics ; Esophageal Neoplasms - therapy ; Microsatellite Repeats ; Digestive System Surgical Procedures - methods ; Stomach Neoplasms - genetics ; Esophagogastric Junction - pathology ; Treatment Outcome ; Genetic Markers ; Stomach Neoplasms - drug therapy ; Adenocarcinoma - therapy ; Esophageal Neoplasms - genetics ; Drug Therapy - methods ; Survival Analysis ; Aged ; Cancer patients ; Care and treatment ; Genetic aspects ; Analysis ; Adjuvant treatment ; Cancer ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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