0000000000021586
AUTHOR
Henryk Pilch
showing 29 related works from this author
Prognostische Bedeutung einer Diabeteserkrankung beim Endometriumkarzinom
2001
Objective: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - Material and methods: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a Χ 2 -test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independ…
Lack of correlation between expression of HIF-1alpha protein and oxygenation status in identical tissue areas of squamous cell carcinomas of the uter…
2004
Abstract Hypoxia inducible factor-1α (HIF-1α) has been proposed as a candidate endogenous marker of tumor hypoxia and as a molecular mediator of hypoxia-driven malignant progression and acquired treatment resistance. In this study, HIF-1α expression in 68 biopsies of oxygenation measurement tracks from squamous cell carcinomas of the uterine cervix of 38 patients was assessed. Expression of HIF-1α was commonly found to increase as a function of distance from microvessels, at the center of tumor cell aggregations, and in the vicinity of necrotic areas. However, there was no correlation of HIF-1α expression with median oxygen tension (oxygen partial pressure; pO2) and hypoxic fractions (hypox…
Naturally processed and HLA-B8-presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer.
2004
Several major histocompatibility complex (MHC) alleles have been reported to present peptides derived from the HPV16 E7 oncoprotein to T cells. We describe an overrepresentation of the HLA-B8 allele (28.44%) in cervical cancer patients as compared to the MHC class I allele frequency in a local healthy control population (18.80%) and the identification of an HLA-B8-binding peptide TLHEYMLDL (HPV16 E77–15), which is able to drive HPV16 E7-specific and MHC class I-restricted T-cell responses in peripheral blood lymphocytes from healthy individuals. TLHEYMLDLspecific T cells recognize the naturally processed and presented peptide on HPV16 cervical cancer cells transfected with the HLA-B8 gene d…
Wertigkeit der Abradathistologie von Endometriumkarzinomen
2002
Objective: We compared immunohistological examination of endometrium biopsy specimen with the results of the immunohistological examination of tumor specimen to analyse the valence of this preoperative examination according to the clinico-pathological findings and overall-survival. Material and Method: Between 1985 and 1995 193 women were treated of an endometrial carcinoma at the University hospital Mainz. In this group we evaluated 41 patients with enough preoperative endometrial biopsy material for a retrospective immunohistochemical analysis and complete follow-up data. The materials from diagnostic curettage were stained and analysed for oestrogen and progesterone receptor status and f…
(A)symptomatic necrotizing arteritis of the female genital tract.
2000
Abstract Aims: The vasculitides represent a heterogenous set of disorders that differ in prognosis and response to therapy. Beside systemic vasculitides, the development of localized forms of arteritis is well known though uncommon and the etiopathogenesis is not yet definitely clear. Methods: Patients with necrotizing arteritis of the female genital tract proven by histology are studied in a retrospective analysis. Results: Three cases of necrotizing arteritis with histological features of panarteritis nodosa apparently confined to the female genital tract are presented. None of these patients had prior history of systemic vasculitis. The acute necrotizing vasculitis was confined only to t…
Perineal Excision of a Large Angiomyxoma in a Young Woman Following Magnetic Resonance and Angiographic Imaging
2001
Abstract Background. Aggressive angiomyxomas are rare, arise from connective tissue of the perineum or the lower pelvis, and affect predominantly young women. Case. We describe an unusual case of aggressive angiomyxoma in which the perineal approach was possible owing to MRI scanning and selective angiography indications. Conclusion. In cases of large aggressive angiomyxomas these diagnostic procedures should make it possible to decide which operative route might be best for the patient.
CD8+CD45RA+CD27-CD28-T-cell subset in PBL of cervical cancer patients representing CD8+T-cells being able to recognize cervical cancer associated ant…
2003
Objective In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. Material and methods Flow-cy…
Different T-cell Receptor (TCR) Zeta Chain Expression in Cervical Cancer and its Precursor Lesions
2006
OBJECTIVE Cervical cancer is associated with infection of epithelial cells with the human papillomavirus (HPV) type 16 and HPV18. A functional signalling machinery in T-cells is required in order to successfully fight and eradicate HPV16+ transformed epithelial cells. One of the key signalling molecules associated with the T-cell receptor (TCR) is the homodimeric zeta chain molecule. MATERIAL AND METHODS 28 formalin fixed und paraffin embedded samples of cervical tissue with cervical intraepithelial lesions CIN I (n = 3), CIN III (n = 7), invasive cervical carcinoma (CC) (n = 13) and normal cervical tissue (n = 5) has been evaluated for HPV-PCR und zeta chain immunohistochemistry. For immun…
Human papillomavirus (HPV) DNA in primary cervical cancer and in cancer free pelvic lymph nodes--correlation with clinico-pathological parameters and…
2001
OBJECTIVE To assess whether the presence of human papilloma virus (HPV) DNA and/or several genotypes of HPV DNA in primary cervical cancer and cancer free pelvic lymph nodes are correlated with several clinicopathological parameters of well-defined prognostic significance and whether virological parameters are predictors of long-term survival in cancer patients. PATIENTS AND METHODS 223 cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the high sensitive polymerase chain reaction (PCR) method followed by …
Glutathione S-transferase T1 and M1 gene defects in ovarian carcinoma
1998
Glutathione S-transferases (GSTs) M1 and T1 are known to be polymorphic in humans. Both polymorphisms are due to gene deletions, which are responsible for the existence of null genotypes. The gene defect of GSTT1 has been reported to be associated with an increased risk of myelodysplastic syndromes, astrocytoma and meningioma. A lack of GSTM1 was associated with tobacco smoke-induced lung and bladder cancer. In this study we examined whether the GSTT1 and/or GSTM1 homozygous null genotypes were associated with an increased risk of ovarian cancer using a multiplex polymerase chain reaction protocol. The GSTT1 null genotype was observed in 14% of the control subjects that had never suffered f…
Differential MHC class II component expression in HPV-positive cervical cancer cells: implication for immune surveillance.
2005
Effective eradication of human papillomavirus (HPV)-positive tumors may require CD8+ and CD4+ T-cell-mediated immune responses. Ectopic expression of MHC class II surface molecules has been described in the context of cervical cancer, but coexpression with other components of the MHC class II antigen presentation pathway has not been addressed. We have evaluated the MHC class II antigen presentation pathway in malignant squamous epithelium of HPV+ cervical cancer lesions by in situ costaining HLA-DR with CLIP or DMA/DMB. Cervical cancer cells exhibit 3 MHC class II phenotypes: (i) DR+/CLIP+ or DM+; (ii) DR+/CLIP- or DM-; and (iii) DR-/CLIP+ or DM+. The identical profile has been identified …
Monoclonal TCR mRNA transcripts are preferentially detected in the TCR variable alpha chain in CD8(+) T-lymphocytes: implications for immunomonitorin…
1999
Clinical trials have started to implement tumor-associated antigens in the form of antigenic peptides in order to augment CD8(+) T-cell responses directed against autologous cancer cells. One of the surrogate markers for successful immunization is the characterization of T-lymphocytes reacting to the immunizing peptide as determined by CDR3-length and DNA-sequence analysis. Most of the recent studies examining ex vivo T-cell responses in patients with cancer have focussed on expression and prevalence of the TCR Beta variable region, predominantly in non-sorted T-cell populations. Here, we show that clonal T-cell receptors (TCRs), as defined by DNA-fragment analysis and DNA-sequencing, appea…
The presence of HPV DNA in cervical cancer: correlation with clinico-pathologic parameters and prognostic significance: 10 years experience at the De…
2001
The objective of this study was to assess whether the presence of human papillomavirus (HPV) DNA and/or several genotypes of HPV DNA in cervical cancer are correlated with several clinicopathologic parameters of well-defined prognostic significance and whether virologic parameters are predictors of long-term survival in cancer patients. Two hundred twenty three cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the highly sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for H…
Expression of tenascin in human cervical cancer--association of tenascin expression with clinicopathological parameters.
1999
Tenascin is an extracellular matrix glycoprotein, relevant for embryonal and fetal development, which is reexpressed in the stroma of benign and malignant tumors. Little is known about the molecular interaction of tenascin during neoplastic transformation and tumor progression in cervical cancer.We studied the expression of tenascin in normal tissue of the cervix uteri, cervical carcinoma in situ, and invasive cervical carcinoma in paraffin sections by immunohistochemistry using a monoclonal antibody. Tenascin immunoreactivity was compared with various prognostic parameters.In normal cervical tissue (n = 5) and in cervical carcinoma in situ (n = 10) only vessel walls showed a weak tenascin …
Hypoxia-stimulated expression of angiogenic growth factors in cervical cancer cells and cervical cancer-derived fibroblasts
2001
It is generally accepted that local growth of solid tumors and their ability to establish distant metastases are dependent on the formation of new blood vessels arising from preexisting ones (angiogenesis). The angiogenic response of the host is mediated by angiogenic molecules that are released from cancer and normal stroma cells, especially fibroblasts. The goal of the present study was to quantitatively compare the expression of the two most important angiogenic growth factors (VEGF, angiogenin) of cervical cancer cells (HeLa and Me-180) with that of cervical cancer-derived fibroblasts (from one tumor/patient) under defined normoxic and hypoxic conditions in vitro. The growth kinetics of…
Carcinoma of the neovagina: case report and review of the literature.
2001
Abstract Background. Carcinoma of the vagina is a rare disease, and it is even more rare in the neovagina. Nevertheless, it has been well described. The aim of this report was to analyze the reported cases and to add observations concerning a risk profile for this rare occurrence of carcinoma. Case report. The 29-year-old patient's history included congenital absence of vagina as a result of Rokitansky–Kuster syndrome. In 1987, when the patient was 17 years old, a neovagina was constructed by dissection between the bladder and the rectum, according to the Warthon method, and the apex of the neovagina was covered with Dura-mater. In 1990 the patient underwent radiation treatment with brachyt…
Evaluation of DNA ploidy and degree of DNA abnormality in benign and malignant melanocytic lesions of the skin using video imaging.
2000
BACKGROUND Making a morphologic distinction between benign and malignant melanocytic tumors of the skin is frequently difficult, especially because “gray zones” between these lesions often exist. DNA image cytometry as an adjuvant method for the diagnosis and prognostic prediction of premalignant lesions and malignant tumors of many other organs is already well established. The aim of this study was to determine whether DNA image cytometry is helpful in distinguishing benign from malignant melanocytic lesions and whether cytometry would give valid information with which to predict the prognoses associated with malignant melanomas. METHODS DNA image cytometry was performed on 127 benign and …
Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein
2003
ABSTRACTHuman papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8+-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8+-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E711-19/20) epitope YMLDLQPET(T) in vitro. CD8+T cells reacting to the HLA-A2-presented peptide from HPV16 E711-19(20)recogni…
Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma.
2001
In cervical carcinomas abnormalities in the MHC class I surface expression are a frequent event, which are often associated with the deficient expression of the peptide transporter subunit TAP1 thereby resulting in impaired T cell response. In order to understand the role of other components of the MHC class I antigen processing machinery (APM) in the immune escape, 16 surgically removed primary cervical carcinoma lesions were analyzed for their mRNA expression of the heterodimeric peptide transporter TAP, the constitutive and interferon (IFN)-gamma inducible proteasome subunits and their activators PA28alpha/beta, various chaperones as well as MHC class I antigens. High expression levels o…
Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor
2002
ABSTRACTWe characterized the T-cell receptor (TCR) repertoire in freshly harvested tumor lesions, in short-term-expanded CD4+tumor infiltrating lymphocytes (TIL) as well as in CD4+and CD8+peripheral blood lymphocytes (PBL) from three patients with cervical cancer. Skewing of the T-cell repertoire as defined by measuring the length of the complementarity-determining region 3 (CDR3) of the TCR VA and VB chains was observed in CD8+PBL, in freshly harvested tumor tissue, as well as in CD4+TIL. Comparative analysis of the TCR repertoire revealed unique monoclonal TCR transcripts within the tumor lesion which were not present in PBL, suggesting selection of TCR clonotypes due to antigenic stimula…
Human Papillomavirus Type 33 E7 Peptides Presented by HLA-DR*0402 to Tumor-Infiltrating T Cells in Cervical Cancer
2000
ABSTRACTSeveral characteristics make human papillomavirus (HPV) amenable to vaccination. Anti-HPV-directed vaccines are based on the observation that HPV E6 and E7 oncoproteins are constitutively expressed in HPV-positive cervical cancer and may serve as tumor rejection antigens. Five HPV types (16, 18, 31, 33, and 45) account for 80% of cervical cancer. Until now, the type of immune response capable of mediating an effective antitumor response has not been defined. In order to define the anticancer-directed immune response in situ, we characterized CD4+and CD8+sorted T cells from peripheral blood lymphocytes, freshly harvested tumor tissue, and tumor-infiltrating lymphocytes (TIL) from a p…
Definition of the HLA-A2 restricted peptides recognized by human CD8+ effector T cells by flow-assisted sorting of the CD8+ CD45RA+ CD28– T cell subp…
2003
SUMMARY In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28− T cells displaying potent immune effector functions upon re-encounter with the nominal antigen. We show that the effector CD8+ CD45RA+ CD28– T cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical lesions as well as in PBL from patients with pulmonary tuberculosis. Flow-cytometric cell sorted CD8+ CD45RA+ CD28– and CD8+ CD45RA+ CD28– T cells were tested for recognition of HLA-A2 restricted peptides de…
Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3).
2007
Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A …
Metallothionein expression in ovarian cancer in relation to histopathological parameters and molecular markers of prognosis
2001
Metallothioneins (MTs) and glutathione constitute the major fractions of intracellular thiol factors. Abundant nucleophilic sulfhydryl groups can interact with many electrophilic substances, including several anti-neoplastic agents, participate in controlling intracellular redox potential, and act as scavengers of reactive oxygen species. In the present study, we examined the relation of MTs (alone and in combination with glutathione) to histopathological parameters and survival time of ovarian cancer patients. Expression of the major MT isoforms (MT-1 and MT-2) was determined by immunohistochemistry on paraffin-embedded tumor specimens from 189 patients, 151 suffering from primary epitheli…
Prognostic Effect of Epithelial Cell Adhesion Molecule Overexpression in Untreated Node-Negative Breast Cancer
2008
Abstract Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. Experimental Design: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. Results: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disea…
The humoral immune system has a key prognostic impact in node-negative breast cancer.
2008
Abstract Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with…
Multivariate independent prognostic factors in endometrial carcinoma: A clinicopathologic study in 181 patients
2003
The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. χ2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor sta…
Improved assessment of T-cell receptor (TCR) VB repertoire in clinical specimens: combination of TCR-CDR3 spectratyping with flow cytometry-based TCR…
2002
ABSTRACTAntigen-specific T-cell responses may be described by combining three categories: (i) the specificity and effector functions of a T-cell population, (ii) the quantity of T-cell responses (i.e., the number of responding T cells within the CD4/CD8 population), and (iii) the “quality” of T cells (defined by the T-cell receptor [TCR] structure). Several methods to measure T-cell responses are now available including evaluation of T-cell precursors using limiting dilution, the enzyme-linked immunospot assay, ex vivo TCR variable (v)-segment analysis determined by flow cytometry, and TCR-CDR3 length analysis (spectratyping), as well as identification of peptide-specific T cells using majo…
Multivariate independent prognostic factors in endometrial carcinoma: A clinicopathologic study in 181 patients: 10 years experience at the Departmen…
2003
The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor s…