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76
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Introduction
Paul Jank (B.Sc. Biotechnology and M.A. Healthcare management) is Head of Translational Research Laboratory at the Institute of Pathology at UMR. He's responsible for central pathology assessments and international, translational research projects, focussed on clinical trials. Key competencies: Biomarker validation; Image analysis; Impact of tumor hetereogeneity and molecular alterations on therapy response and survival; Biobanking.
https://orcid.org/0000-0001-7076-0476
Current institution
Additional affiliations
March 2019 - December 2021
January 2016 - March 2019
Education
November 2017 - December 2021
October 2012 - October 2015
September 2009 - June 2012
Publications
Publications (76)
Activating PIK3CA mutations, present in up to 40% of hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (Her2 −) breast cancer (BC) patients, can be effectively targeted with the alpha isoform-specific PI3K inhibitor Alpelisib. This treatment significantly improves outcomes for HR + , Her2 − , and PIK3CA-mutated met...
Introduction Several studies demonstrated the de novo-formation of lymphatic vessels in tumor-draining lymph nodes (LN), partly preceding lymphatic metastases. This “lymphovascular niche” supposedly facilitates survival of metastatic tumor cells. This study aims at evaluating the previously observed immunophenotypic variations of subcapsular endoth...
Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expressi...
Purpose:
The PI3K signaling pathway is frequently dysregulated in breast cancer (BC), and mutations in PIK3CA, are relevant for therapy resistance in HER2pos BC. Mutations in exons 9 or exon 20 may have different impact on response to neoadjuvant chemotherapy-based treatment regimens.
Experimental design:
We investigated PIK3CA mutations in 1691...
566
Background: The concept of intrinsic subtyping has been an important step for understanding of breast cancer (BC) as a heterogenous disease. However, these subtypes are not adapted to therapy-induced molecular plasticity. We have evaluated a high-risk luminal BC clinical trial cohort to identify new additional adaptive BC subtypes based on mole...
Background:
Despite recent advances in personalized medicine, conventional chemotherapy remains a backbone in breast cancer therapy. Thus, identifying markers predicting sensitivity or resistance to individual chemotherapeutics is of great importance.
Methods:
In the EpiTax neoadjuvant trial, enrolling patients between 1997-2003, patients with prim...
Background
The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays a crucial role in regulating the immune system's response to tumors, but its exact role in cancer, especially in high-grade serous ovarian cancer (HGSOC), remains controversial. We aimed to investigate the prognostic impact of IDO1 expression and its correlation with tumor-infiltratin...
Complementary to synaptophysin and chromogranin A, insulinoma-associated protein 1 (INSM1) has emerged as a sensitive marker for the diagnosis of neuroendocrine neoplasms. Since there are no comparative data regarding INSM1 expression in conventional colorectal adenocarcinomas (CRCs) and colorectal mixed adenoneuroendocrine carcinomas/neuroendocrin...
Background
Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of p...
In breast cancer, the current guideline for pathological workup includes recommendations for advanced molecular analysis of certain predictive molecular markers in addition to basic immunohistochemical diagnostics. These markers are determined depending on tumor stage, including sequencing techniques and immunohistochemical methods. This comprises...
Background: It is well known that immunological pathways are relevant for response to classical neoadjuvant chemotherapy as well as combined chemo-immunotherapy. In addition, it has been shown that combined chemo-immunotherapy significantly improves survival, even in the context of only moderate effects on pCR. Due to the window therapy with durval...
Background: EndoPredict is a prognostic and predictive gene expression assay that provides an EPclin risk score, which can be used to identify individuals with low enough risk of distant breast cancer recurrence that they may forgo chemotherapy. In clinical studies, EndoPredict has been validated to predict risk of distant recurrence up to 15 years...
Immunohistochemical evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status stratify the different subtypes of breast cancer and define the treatment course. Triple-negative breast cancer (TNBC), which does not register receptor overexpression, is often associated with worse patient prognosis. Mas...
Several studies have demonstrated the de novo formation of lymphatic vessels or the reorganization of lymphatic sinus in tumor-draining lymph nodes, partly preceding the detection of lymphatic metastases. This “lymphovascular niche”is supposed to facilitate the survival of metastatic tumor cells. Few studies on nodal lymphangiogenesis in invasive b...
In breast cancer, the current guideline for pathological workup includes recommendations for advanced molecular analysis of certain predictive molecular markers in addition to basic immunohistochemical diagnostics. These markers are determined depending on tumor stage, including sequencing techniques and immunohistochemical methods. This comprises...
The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade...
The diagnostic evaluation of homologous recombination deficiency (HRD) is central to define targeted therapy strategies for patients with ovarian carcinoma. In this project, we evaluated HRD in 514 ovarian carcinoma samples by next-generation sequencing of DNA libraries including biotinylated probes covering BRCA1/BRCA2 and 26,523 SNPs using the st...
Background
Pathological TNM staging (pTNM) is the strongest prognosticator in colorectal carcinoma (CRC) and the foundation of its post-operative clinical management. Tumours that invade pericolic/perirectal adipose tissue generally fall into the pT3 category without further subdivision.
Methods
The histological depth of invasion into the pericoli...
Detection of circulating tumor cells (CTCs) has been established as an independent prognostic marker in solid cancer. Multiparametric phenotyping of CTCs could expand the area of application for this liquid biomarker. We evaluated the Amnis® brand ImageStream®X MkII (ISX) (Luminex, Austin, TX, USA) imaging flow cytometer for its suitability for pro...
581
Background: It is commonly anticipated that a high tumor mutational burden (TMB) is a predictor of response to immune checkpoint blockade (ICB). We previously showed that triple-negative breast cancer (TNBC) from the GeparNuevo study with high TMB displayed increased response both to neoadjuvant chemo-ICB with durvalumab but also to chemotherap...
Background:
Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy might be beneficial. Therefore, a combination of the photosensitizer Hyper...
Background/aim:
Mucinous ovarian carcinoma (mOC) is a rare subtype with distinct clinical characteristics and biological behavior that differentiate them from other epithelial ovarian cancers. This study aimed to evaluate BMI-1 expression as a potential target for therapeutic approaches in advanced stage mOC.
Materials and methods:
We performed...
Background:
Altered expression levels and structural variations in the vascular endothelial growth factor (VEGF) have been found to play important roles in cancer development and to be associated with the overall survival and therapy response of cancer patients. Particularly VEGF-A and its splice variants have been found to affect physiological an...
Background: Breast cancer is one of the most common malignancies during pregnancy. Although breast cancer in pregnancy (BCP) is still a rare event (1 in 3000 to 10000 pregnancies), the incidence is likely to increase as more women tend to delay childbearing into later life and the overall lifetime cancer risk increases with age. Pregnancy presents...
Background: Luminal, i.e., estrogen receptor (ER)-positive breast cancer (BC) is a heterogeneous disease in terms of tumor progression, therapy response, and relapse. Additional biomarkers with a prognostic and predictive impact would facilitate advanced patient stratification and can reveal advanced therapeutic options for individual patients suff...
Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these mutations are known as mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence...
Background
Risk assessment on the molecular level is important in predictive pathology to determine the risk of metastatic disease for ERpos, HER2neg breast cancer. The gene expression test EndoPredict (EP) was trained and validated for prediction of a 10-year risk of distant recurrence to support therapy decisions regarding endocrine therapy alone...
Estrogen receptor‐positive breast cancer is a highly prevalent but heterogeneous disease among women. Advanced molecular stratification is required to enable individually most efficient treatments based on relevant prognostic and predictive biomarkers. First objective of our study was the hypothesis‐driven discovery of biomarkers involved in tumor...
Background: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy might be beneficial. Therefore, a combination of the photosensitizer Hyperi...
Background:
Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated.
Methods:
SATB2 expression was analysed in 1039 CRCs and...
Background
Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1–10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation prof...
The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed dea...
Background:
Colorectal mixed adenoneuroendocrine carcinomas (MANECs) are clinically highly aggressive neoplasms. MANECs are composed of variable adenocarcinoma components combined with morphologically distinct neuroendocrine carcinoma components, which are confirmed by synaptophysin immunohistochemistry, the gold standard marker of a neuroendocrin...
Estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2 immunohistochemistry (IHC) together with HER2 in situ hybridization (ISH) are utilized to classify invasive breast cancer (IBC) into predictive molecular subtypes. As IHC evaluation may be hampered by analytical errors, gene expression assays could offer a reliable alternative. In...
[This corrects the article DOI: 10.1371/journal.pone.0238021.].
Background
Current genetic and genomic tests measuring homologous recombination deficiency (HRD) show limited predictive value. This study compares the performance of an immunohistology-based RAD51 test with genetic/genomic tests to identify patients with HRD primary triple-negative breast cancer (TNBC) and evaluates its accuracy to select patients...
Background
Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy has been established as a novel treatment approach for peritoneal sarcomatosis. Despite promising clinical reports, there is still a lack of knowledge regarding optimal drug usage and local effects. Therefore, we intended to establish a murine animal mode...
Background: Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy has been established as a novel treatment approach for peritoneal sarcomatosis. Despite promising clinical reports, there is still a lack of knowledge regarding optimal drug usage and local effects. Therefore, we intended to establish a murine animal mod...
Background: Risk assessment on molecular level is becoming more common in modern pathology to determine the recurrence risk for patients diagnosed with estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer (BC). The gene expression test EndoPredict (EP) was trained and validated to predict a 10-year risk of distant recurrence to sup...
Constitutively active estrogen receptor-α (ER/ ESR1 ) mutations have been identified in approximately one third of ER+ metastatic breast cancer. Although these mutations are known mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of...
Background
Different endogenous and exogenous mutational processes act over the evolutionary history of a malignant tumor, driven by abnormal DNA editing, mutagens or age-related DNA alterations, among others, to generate the specific mutational landscape of each individual tumor. The signatures of these mutational processes can be identified in la...
Background:
Risk assessment on molecular level is becoming more common in modern pathology to determine the recurrence risk for patients diagnosed with estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer (BC). The gene expression test EndoPredict (EP) was trained and validated to predict a 10-year risk of distant recurrence to su...
CD34+ fibroblasts are constitutive stromal components of virtually all organs, including the mammary stroma, being involved in matrix synthesis, antigen presentation, and tumor-associated stromal remodeling. The most common subtype of invasive breast carcinoma, invasive carcinoma of no special type (IBC-NST), is known for its stromal loss of CD34+...
Altered expression and function of the transcription factor cyclic AMP response-binding protein (CREB) has been identified to play an important role in cancer and is associated with the overall survival and therapy response of tumor patients. This review focuses on the expression and activation of CREB under physiologic conditions and in tumors of...
Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cy...
With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied...
Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research comm...
Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management frame...
Background
The predictive value of tumor mutational burden (TMB), alone or in combination with an immune gene expression profile (GEP), for response to neoadjuvant therapy in early triple negative breast cancer (TNBC) is currently not known, neither for immune checkpoint blockade (ICB) nor conventional chemotherapy.
Patients and Methods
We obtaine...
The antiangiogenic splice variant VEGF-A165b is downregulated in a variety of cancer entities, but little is known so far about circulating plasma levels. The present analysis addresses this question and examines circulating VEGF-A/VEGF-A165b levels in a collective of female high-risk breast cancer patients over the course of treatment. Within the...
3075
Background: Hormone receptors, HER2 and Ki-67 are prognostic values typically determined for breast cancer (BC) outcome and prediction of therapy response. A RT-qPCR based system, the Xpert Breast Cancer STRAT4, can be used to classify BC tissues regarding their hormone receptor status, HER2 and proliferation via Ki-67. We compared mRNA expres...
e17091
Background: Previously four molecular subtypes of high grade serous ovarian cancer (HGSOC) with distinct biological features and clinical outcome have been described: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative). Using Nanostring technique and a minimal signature of 39 classifier genes could reproduce th...
Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syn...
Purpose: Next-generation sequencing (NGS) can be used for comprehensive investigation of molecular events in breast cancer. We evaluated the relevance of genomic alterations for response to neoadjuvant chemotherapy (NACT) in the GeparSepto trial.
Experimental Design: Eight hundred fifty-one pretherapeutic formalin-fixed paraffin-embedded (FFPE) cor...
Precise histological classification of epithelial ovarian cancer (EOC) subtypes is important for personalized treatment. The image, designed by Maria Hänel, illustrates the potential of imaging mass spectrometry combined with machine learning methods to explore spatial proteomic levels, enabling the classification of EOC histological subtypes. Appl...
Low-grade serous ovarian carcinoma (LGSOC) has recently come up as a distinct rare entity of epithelial ovarian cancer. Predictive and prognostic markers are not well studied yet. As Ki-67 and hormone receptors (HR) has been established as relevant cancer biomarkers in several malignant tumors we evaluated Ki-67 and HR expression rates by immunohis...
APOBEC3 enzymes are part of the innate immune system and they are important in retroviral defense. The number of mutations in ovarian cancer increases with rising levels of APOBEC3B mRNA. We could confirm that APOBEC3B mRNA is upregulated in ovarian cancer cell lines and in ovarian cancer tissue. We evaluated APOBEC3B expression in histologically d...
Background: Targeted next-generation sequencing (NGS) enables investigation of key molecular events in breast cancer (BC) and driver genes. In this study we evaluated the relevance of mutations in 15 cancer genes and copy number amplifications in 8 cancer genes for response to neoadjuvant therapy in the GeparSepto cohort. The pCR rate was significa...
