@phdthesis{Frey2018,
  author    = {Frey, Lea Sarah},
  title     = {Retrospektive Analyse zur Bedeutung des 21-Gen-Tests (OncotypeDX®) f{\"u}r die Indikationsstellung zu einer adjuvanten Chemotherapie bei Hormonrezeptor-positivem, Her2/neu-negativem Mammakarzinom},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156908},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Bei der postoperativen Therapieplanung des Mammakarzinoms treten immer wieder Entscheidungsgrenzf{\"a}lle auf, bei denen keine sicheren Argumente f{\"u}r oder gegen eine adjuvante Chemotherapie gefunden werden k{\"o}nnen. Bei 50 Hormonrezeptor-positiven, Her2/neu-negativen Mammakarzinomen ohne oder mit nur geringer nodaler Metastasierung (max. pT1a) wurde zus{\"a}tzlich zu den konventionellen klinisch-pathologischen Risikofaktoren der OncotypeDX®-Multigentest veranlasst. In der Tumorkonferenz wurde bereits vor Eingang des Testergebnisses ein Votum f{\"u}r oder gegen eine Chemotherapie auf Basis konventioneller Parameter protokolliert; die definitive Therapieempfehlung erfolgte nach Vorliegen des Multigentest-Ergebnisses. 32 Mammakarzinome (64 \%) zeigten einen niedrigen, 26 (32 \%) einen mittleren und 3 (6 \%) einen hohen Recurrence-Score (RS). In vielen F{\"a}llen konnte das OncotypeDX®-Ergebnis eine auf der Basis konventioneller Parameter getroffene Therapieentscheidung st{\"u}tzen. In f{\"u}nf F{\"a}llen wurde eine zun{\"a}chst favorisierte Entscheidung f{\"u}r eine adjuvante Therapie revidiert. In drei F{\"a}llen wurde eine zun{\"a}chst nicht geplante Chemotherapie empfohlen. Allerdings f{\"u}hrte in einigen F{\"a}llen auch eine niedrige oder intermedi{\"a}re Risikokonstellation in der OncotypeDX®-Testung nicht dazu, von einer adjuvanten Chemotherapie abzuraten. Insgesamt spricht das Ergebnis nicht daf{\"u}r, einen Multigentest als Standardmethode einzusetzen. Vielmehr sollten zun{\"a}chst die konventionellen, insbesondere die histopathologischen und immunhistochemischen Parameter mit großer Sorgfalt erhoben und analysiert werden. Im Zweifelsfall und nach Kosten-Nutzen-Abw{\"a}gung kann ein Multigentest jedoch ein weiteres hilfreiches Argument f{\"u}r oder gegen eine bestimmte Therapieempfehlung liefern.},
  subject      = {Mammakarzinom},
  language  = {de}
}
@article{DirksHaaseCantaertetal.2022,
  author    = {Dirks, Johannes and Haase, Gabriele and Cantaert, Tineke and Frey, Lea and Klaas, Moritz and Rickert, Christian H. and Girschick, Hermann and Meffre, Eric and Morbach, Henner},
  title     = {A novel AICDA splice-site mutation in two siblings with HIGM2 permits somatic hypermutation but abrogates mutational targeting},
  series = {Journal of Clinical Immunology},
  volume    = {42},
  journal   = {Journal of Clinical Immunology},
  number    = {4},
  doi       = {10.1007/s10875-022-01233-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324253},
  pages     = {771-782},
  year      = {2022},
  abstract  = {Hyper-IgM syndrome type 2 (HIGM2) is a B cell intrinsic primary immunodeficiency caused by mutations in AICDA encoding activation-induced cytidine deaminase (AID) which impair immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). Whereas autosomal-recessive AID-deficiency (AR-AID) affects both CSR and SHM, the autosomal-dominant form (AD-AID) due to C-terminal heterozygous variants completely abolishes CSR but only partially affects SHM. AR-AID patients display enhanced germinal center (GC) reactions and autoimmune manifestations, which are not present in AD-AID, suggesting that SHM but not CSR regulates GC reactions and peripheral B cell tolerance. Herein, we describe two siblings with HIGM2 due to a novel homozygous AICDA mutation (c.428-1G > T) which disrupts the splice acceptor site of exon 4 and results in the sole expression of a truncated AID variant that lacks 10 highly conserved amino acids encoded by exon 4 (AID-ΔE4a). AID-ΔE4a patients suffered from defective CSR and enhanced GC reactions and were therefore indistinguishable from other AR-AID patients. However, the AID-ΔE4a variant only partially affected SHM as observed in AD-AID patients. In addition, AID-ΔE4a but not AD-AID patients revealed impaired targeting of mutational hotspot motives and distorted mutational patterns. Hence, qualitative defects in AID function and altered SHM rather than global decreased SHM activity may account for the disease phenotype in these patients.},
  language  = {en}
}
@article{VoelkerWeigelStrehletal.2018,
  author    = {V{\"o}lker, Hans-Ullrich and Weigel, Michael and Strehl, Annette and Frey, Lea},
  title     = {Levels of uPA and PAI-1 in breast cancer and its correlation to Ki67-index and results of a 21-multigene-array},
  series = {Diagnostic Pathology},
  volume    = {13},
  journal   = {Diagnostic Pathology},
  number    = {67},
  doi       = {10.1186/s13000-018-0737-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176960},
  year      = {2018},
  abstract  = {Background: Conventional parameters including Ki67, hormone receptor and Her2/neu status are used for risk stratification for breast cancer. The serine protease urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumour invasion and metastasis. Increased concentrations in tumour tissue are associated with more aggressive potential of the disease. Multigene tests provide detailed insights into tumour biology by simultaneously testing several prognostically relevant genes. With OncotypeDX\(^{®}\), a panel of 21 genes is tested by means of quantitative real-time polymerase chain reaction. The purpose of this pilot study was to analyse whether a combination of Ki67 and uPA/PAI-1 supplies indications of the result of the multigene test. Methods: The results of Ki67, uPA/PAI-1 and OncotypeDX\(^{®}\) were analysed in 25 breast carcinomas (luminal type, pT1/2, max pN1a, G2). A statistical and descriptive analysis was performed. Results: With a proliferation index Ki67 of < 14\%, the recurrence score (RS) from the multigene test was on average in the low risk range, with an intermediate RS usually resulting if Ki67 was > 14\%. Not elevated values of uPA and PAI-1 showed a lower rate of proliferation (average 8.5\%) than carcinomas with an increase of uPA and/or PAI-1 (average 13.9\%); p = 0.054, Student's t-test. When Ki67 was > 14\% and uPA and/or PAI-1 was raised, an intermediate RS resulted. These differences were significant when compared to cases with Ki67 < 14\% with non-raised uPA/PAI-1 (p < 0.03, Student's t-test). Without taking into account the proliferative activity, an intermediate RS was also verifiable if both uPA and PAI-1 showed raised values. Conclusion: A combination of the values Ki67 and uPA/PAI-1 tended to depict the RS to be expected. From this it can be deduced that an appropriate analysis of this parameter combination may be undertaken before the multigene test in routine clinical practice. The increasing cost pressure makes it necessary to base the implementation of a multigene test on ancillary variables and to potentially leave it out if not required in the event of a certain constellation of results (Ki67 raised, uPA and PAI-1 raised).},
  language  = {en}
}