Publications by authors named "Joachim Alfer"

15 Publications

  • Page 1 of 1

Endometrial Dating Method Detects Individual Maturation Sequences During the Secretory Phase.

In Vivo 2020 Jul-Aug;34(4):1951-1963

Fertility-Center Munich, Munich, Germany.

Background/aim: This study assessed whether a new immunohistochemical dating method allows precise endometrial dating allowing optimal timing for embryo transfer.

Patients And Methods: A novel method was used for endometrial dating, with parameters including menstrual cycle days, Noyes histological criteria, along with immunohistochemical expression pattern of estrogen and progesterone receptors and proliferation marker Ki-67. Endometrial maturation was analyzed on days +5 to +10 after ovulation or progesterone administration in 217 biopsies from 151 subfertile patients during the secretory phase.

Results: Endometrial maturation varied individually, occurring 1.68±1.67 days late. Comparison of histological maturation with clinical days after ovulation showed a delay of about 2 days.

Conclusion: Endometrial maturation requires 8 days, rather than the expected 6 days, to reach the histological mid-secretory phase. This is not a delay and is also seen in fertile patients. The new analysis method used is superior to that using Noyes criteria alone and provides a better basis for determining conditions for optimal timing of embryo transfers.
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http://dx.doi.org/10.21873/invivo.11992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439867PMC
April 2020

Histological villous maturation in placentas of complicated pregnancies.

Histol Histopathol 2020 Aug 27;35(8):849-862. Epub 2020 Jan 27.

Department of Anatomy and Embryology, Maastricht University Medical Center+, Maastricht, the Netherlands.

Chorioamnionitis and preeclampsia account for the majority of preterm births worldwide. Thus far, adequate methods for early detection or prevention of these diseases are lacking. In preeclampsia, accelerated villous maturation is believed to compensate placental insufficiency. However, little is known about the effects of placental inflammation in chorioamnionitis on villous maturation. Therefore, we established a set of morphological parameters to evaluate histological villous maturity in pregnancies complicated by chorioamnionitis and preeclampsia. Preterm placentas complicated by chorioamnionitis or preeclampsia were compared to idiopathic preterm placentas and term controls. Histological villous maturation was analyzed by means of 17 histological markers. Fourteen of these markers provided information on absolute and relative numbers of the terminal villi (TV), the extent of their vascularization (using CD31-stained sections) and their exchange capacities. In addition, the numbers of syncytial bridges, syncytial apoptotic knots and shed syncytiotrophoblasts were counted. Accelerated villous maturation in preeclampsia was demonstrated by means of histological villous remodeling and confirmed by 11 relevant markers. Chorioamnionitis, however, only showed increased area of fetal capillaries. In preeclampsia, placentas may transition from growth to maturation earlier than placentas in normal pregnancies, whereas in chorioamnionitis placental changes are more acute and therefore less elaborated at a structural level. Regression analysis suggests the number of all villi and the number of terminal villi as a percentage of all villi as parameters to evaluate histological villous maturity in preeclamptic placentas and to assist diagnosis. However, we would recommend to analyze all 11 relevant parameters to judge placental maturity in detail.
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http://dx.doi.org/10.14670/HH-18-205DOI Listing
August 2020

Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients?

Geburtshilfe Frauenheilkd 2017 Jul 17;77(7):756-764. Epub 2017 Jul 17.

Institute of Molecular and Cellular Anatomy, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Introduction: This study investigated subfertile patients with abnormally thin endometrium after infertility treatment. As they had adequate serum concentrations of hormones, an endometrial factor for subfertility was suspected.

Methods: To elucidate the cause of subfertility, endometrial biopsies were taken in each patient in the late proliferative and mid-secretory phases of one menstrual cycle. Endometrial biopsies from women with normal menstrual cycles and confirmed fertility who were undergoing hysterectomy for benign uterine disease were used as positive controls. The tissue samples were investigated for steroid hormone receptor expression and for the proliferation marker Ki-67. Immunohistochemistry was performed with antibodies against the marker molecules for endometrial receptivity - β integrin, VEGF, LIF, and CD56 (large granular lymphocytes, LGLs).

Results: The steroid hormone receptors for estrogen (E2) and progesterone (P) were expressed normally (at the first biopsy) and were down-regulated (at the second biopsy) within the cycle. Strikingly, all of the marker molecules investigated showed negative or weak and inadequate expression in the mid-secretory phase. Numbers of LGLs remained as low as in the proliferative phase. In contrast, fertile patients were found to express these marker molecules distinctly in the mid-secretory phase.

Conclusions: It may be hypothesized that a severe deficiency of these angiogenesis-related marker molecules leads to defective development of the endometrium, which remains thin. Deficient angiogenetic development may thus provide an explanation for the endometrial factor that causes infertility. Further investigations will need to focus on identifying the regulating factors that act between steroid receptor activation and the expression of these marker molecules.
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http://dx.doi.org/10.1055/s-0043-111899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514021PMC
July 2017

Evidence of H3 K27M mutations in posterior fossa ependymomas.

Acta Neuropathol 2016 10 18;132(4):635-7. Epub 2016 Aug 18.

Division of Pediatric Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.

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http://dx.doi.org/10.1007/s00401-016-1608-3DOI Listing
October 2016

A randomized phase 2 study comparing EC or CMF versus nab-paclitaxel plus capecitabine as adjuvant chemotherapy for nonfrail elderly patients with moderate to high-risk early breast cancer (ICE II-GBG 52).

Cancer 2015 Oct 25;121(20):3639-48. Epub 2015 Jun 25.

German Breast Group, Neu-Isenburg, Germany.

Background: Although greater than 40% of breast cancers occur in patients aged ≥65 years, these individuals are frequently undertreated. Taxane-based adjuvant chemotherapy is considered the treatment of choice but to the authors' knowledge has only limited evidence in elderly patients.

Methods: Patients aged ≥65 years with a Charlson comorbidity index ≤2 and pT1/2 pN0/1 disease and either human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative, grade 3 (according to Common Terminology Criteria for Adverse Events [version 3.0]), high uPA/PAI-1 or any stage pT3/4 pN2/3 breast cancer were randomized to receive 4 cycles of adjuvant epirubicin and cyclophosphamide (EC) (epirubicin at a dose of 90 mg/m(2) and cyclophosphamide at a dose of 600 mg/m(2) intravenously [iv] on day 1 every 3 22 days) or 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (cyclophosphamide at a dose of 500 mg/m(2), methotrexate at a dose of 40 mg/m(2), and 5-fluorouracil at a dose of 600 mg/m(2) iv on days 1 plus 8 every 29 days) versus 6 cycles of nab-paclitaxel and capecitabine (nPX) (nab-paclitaxel at a dose of 100 mg/m(2) iv on days 1, 8, and 15 every 21 days with 1 week of rest every 6 weeks plus capecitabine at a dose of 2000 mg/m(2) orally on days 1-14 every 21 days). Primary endpoints were treatment discontinuations and overall frequency of adverse events.

Results: Thirteen of 198 patients (6.6%) discontinued EC/CMF and 69 of 193 patients (35.8%) discontinued nPX (P<.001) with 1 and 5 deaths observed during treatment, respectively. Grade 3 to 5 adverse events were more frequent among patients treated with EC/CMF (90.9%) than among those treated with nPX (64.8%) (P<.001), with hematological toxicities being more frequent with EC/CMF (88.4% vs 22.3%; P<.001), but nonhematological toxicities (hand-foot syndrome, diarrhea, mucositis, fatigue, sensory neuropathy, thromboembolisms, and metabolic disorders) being more frequent with nPX (58.5% vs 18.7%; P<.001). None of the geriatric scores (Charlson comorbidity index, Vulnerable Elders Survey [VES-13], Instrumental Activities of Daily Living [IADL], and G8) independently predicted grade 3 to 5 toxic events or treatment discontinuations. No differences in survival between the treatment groups were observed after 22.8 months.

Conclusions: Compared with EC/CMF, treatment with nPX led to more treatment discontinuations and nonhematological toxicities in elderly patients with moderate or high-risk breast cancer.
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http://dx.doi.org/10.1002/cncr.29506DOI Listing
October 2015

Lactotrophs: the new and major source for VEGF secretion and the influence of ECM on rat pituitary function in vitro.

Oncol Rep 2015 May 13;33(5):2129-34. Epub 2015 Mar 13.

Department of Pathology Kaufbeuren-Ravensburg, D-88212 Ravensburg, Germany.

Vascular endothelial growth factor (VEGF) plays a pivotal role in pituitary endocrine function by influencing fenestration and blood vessel growth. Folliculostellate (FS) cells, which represent only a small number of pituitary cells, are recognized to produce VEGF. Tissue sections and primary pituitary cell cultures from rat pituitary glands were performed to co-localize VEGF and pituitary lactotrophs, which represents nearly 50% of all pituitary cells, by immunofluorescence. VEGF is co-localized with prolactin-producing cells in vivo and in vitro. FS cells are present infrequently in vivo (1.6%) and in vitro (2.4%). Culture supernatants were analyzed for the presence of VEGF by ELISA. VEGF levels are always significantly lower in supernatants from the cells that are seeded on Matrigel extracellular matrix (ECM) compared to the cells grown on plastic. Lower VEGF concentrations in supernatants from the pituitary cells cultured on ECM may reflect a more adequate cell environment compared to culture on plastic. These results demonstrate for the first time, that VEGF is expressed by lactotrophs, which outnumber FS cells. These results are of potential clinical relevance especially in oncology for the interpretation of studies investigating anti‑angiogenic treatment of pituitary tumors.
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http://dx.doi.org/10.3892/or.2015.3851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391590PMC
May 2015

Receptor tyrosine kinase inhibitors: Are they real tumor killers?

Int J Cancer 2016 Feb 11;138(3):540-54. Epub 2015 Mar 11.

Institute of Pathology, Technical University Dresden, Dresden, Germany.

Inhibiting tumor growth by targeting the tumor vasculature was first proposed by Judah Folkman almost 40 years ago. Since then, different approaches and numerous drugs and agents have been developed to achieve this goal, either with the aim of inhibiting tumor neoangiogenesis or normalizing the tumor vasculature. Among the most promising therapeutic targets are receptor tyrosine kinases (RTKs), some of which are predominantly expressed on tumor endothelial cells, although they are sometimes also present on tumor cells. The majority of RTK inhibitors investigated over the past two decades competes with ATP at the active site of the kinase and therefore block the phosphorylation of intracellular targets. Some of these drugs have been approved for therapy, whereas others are still in clinical trials. Here, we discuss the scientific basis, current status, problems and future prospects of RTK inhibition in anti-tumor therapy.
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http://dx.doi.org/10.1002/ijc.29499DOI Listing
February 2016

Increased angiogenesis and FGFR protein expression indicate a favourable prognosis in bladder cancer.

Virchows Arch 2014 Dec 19;465(6):687-95. Epub 2014 Oct 19.

Institute of Pathology, University Hospital Erlangen, Krankenhausstrasse 8-10, 91054, Erlangen, Germany.

Compared to other members of the fibroblast growth factor receptor (FGFR) family, only few studies investigate FGFR3 in tumour angiogenesis. We investigated the connection between angiogenesis and FGF/FGFR expression including FGFR3 mutation status in urothelial carcinomas. Immunohistochemistry was performed in invasive and non-invasive urothelial cancers of 61 patients. Protein expression of CD31, factor VIII (FVIII), FGF-1/2, FGFR1, FGFR3 and FGFR4 and FGFR3 mutation status were evaluated. Morphometric assessment of angiogenesis including microvessel count (MVC) and vascular surface area (VSA) was analysed. Correlation and survival analyses (overall survival (OS) and disease-free survival (DFS)) with univariate and multivariate analyses were performed. CD31 values (MVC and VSA) significantly correlated with OS and DFS. OS and DFS were significantly better in patients with FGFR3 overexpression. Multivariate analysis revealed FGFR3 protein expression and tumour grading (WHO classification 2004) as independent prognostic factors of OS and VSA of CD31 and FGFR3 protein expression of DFS. FGFR3 mutation status was correlated with VSA measured by FVIII. FGFR3 may be able to induce a pro-angiogenic phenotype in urothelial carcinomas and significantly influence prognosis. Consequently, FGFR3 is a potential therapeutic target also from the angiogenesis perspective.
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http://dx.doi.org/10.1007/s00428-014-1672-9DOI Listing
December 2014

Mammaglobin 1: not only a breast-specific and tumour-specific marker, but also a hormone-responsive endometrial protein.

Histopathology 2012 Nov 20;61(5):955-65. Epub 2012 Sep 20.

Institute of Molecular and Cellular Anatomy, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Aims: The secretoglobin mammaglobin 1 (MGB1) is strongly expressed in breast tumours, and is therefore used to detect breast cancer metastases, although it has also been detected in other tissues. The aim of this study was to examine MGB1 expression and its hormonal regulation in human endometrium to further investigate the use of MGB1 as a marker molecule.

Methods And Results: Mammaglobin 1 expression was assessed immunohistochemically in endometrial samples from 60 normal fertile patients throughout the menstrual cycle, in 49 endometriotic tissue samples, in 15 endometrial adenocarcinomas, and in 36 breast carcinomas. In addition, 25 endometrial samples were analysed by western blot and quantitative real-time reverse transcription polymerase chain reaction. To prove hormonal regulation, primary endometrial epithelial cells were cultured with 17β-oestradiol and promegestone. MGB1 was detected in human endometrial tissue, with peak expression during the luteal phase, in 31% of endometriotic samples, in 53% of endometrial adenocarcinomas, and in 64% of breast carcinomas. MGB1 mRNA expression was increased in vitro by hormonal treatment.

Conclusions: Our data show that MGB1 expression is not restricted to normal and malignant breast tissue. Besides its documented occurrence in endometriotic and malignant endometrial tissues, MGB1 is also expressed in normal human endometrium, and such expression is controlled by steroid hormones.
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http://dx.doi.org/10.1111/j.1365-2559.2012.04290.xDOI Listing
November 2012

Class I histone deacetylase expression in the human cyclic endometrium and endometrial adenocarcinomas.

Hum Reprod 2007 Nov 29;22(11):2956-66. Epub 2007 Aug 29.

Department of Anatomy and Reproductive Biology, RWTH University of Aachen, Wendlingweg 2, 52074, Aachen, Germany.

Background: Class I histone deacetylases (HDACs) and acetylases (HATs) are members of transcriptional pre-initiation complexes assembled by steroid hormone receptors. Recently, HDAC inhibitors were shown to enhance differentiation of endometrial fibroblasts and endometrial adenocarcinomas. However, there is only rare information on HDAC and HAT expression in the human endometrium.

Methods: HDAC-1, -2, -3 and HAT (PCAF and GCN5) mRNA expression was studied in tissue from premenopausal women undergoing hysterectomy by real-time or semiquantitative RT-PCR. HDAC protein expression was assessed by Western Blot and immunohistochemistry. In endometrial adenocarcinomas (n = 17), HDAC-1 expression was studied by immunohistochemistry.

Results: In the human endometrium, HDAC-1, -2, -3 and PCAF mRNA are expressed without cyclical changes. Western blot analysis demonstrated that HDAC-2 protein expression was slightly, but significantly elevated in the secretory phase (P < 0.01 versus day 5-8), whereas HDAC-1 and -3 protein expression was constitutive throughout the menstrual cycle. By immunohistochemistry, nuclear expression of HDAC proteins was detected in all endometrial cell types. In the case of HDAC-3, immunostaining was significantly reduced in the endometrial surface epithelium on day 6-10 (P < 0.01 versus days 15-18 and 24-28). Compared to normal endometrium, a high proportion of endometrial adenocarcinomas showed impaired HDAC-1 protein expression in the epithelial and stromal compartment.

Conclusions: Class I HDACs and HATs are expressed in the human endometrium throughout the menstrual cycle, suggesting the cyclic endometrium as a potential target for HDAC inhibitors. We hypothesis that alterations of HDAC and/or HAT expression are potentially involved in impaired endometrial differentiation.
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http://dx.doi.org/10.1093/humrep/dem241DOI Listing
November 2007

Cytokeratin expression patterns for distinction of odontogenic keratocysts from dentigerous and radicular cysts.

J Oral Pathol Med 2005 Oct;34(9):558-64

Department of Oral and Maxillofacial Surgery, Aachen University of Technology, Aachen, Germany.

Background: The clinical outcome of treatment of odontogenic cysts differs depending on separate entities. Particular clinical relevance must be attached to the distinction between odontogenic keratocysts, which have an evident tendency to recur, and other odontogenic cysts. The aim of this study was to evaluate cytokeratin (CK) expression patterns as an additional tool for characterization of different cysts as the histomorphologic appearance often is not decisive.

Methods: Thirty cases of dentigerous and radicular cysts respectively as well as 15 cases of odontogenic keratocysts were considered. Expression of CK 5/6, 7, 10, 13, 17, 19 and 20 was determined in addition to Ki-67 immunohistochemically.

Results: Expression of CK 17 was discernible in 93.3% of the odontogenic keratocysts, but only in 35.0% of dentigerous and radicular cysts under study (P < 0.001). CK 19 could be detected in 48.3% of dentigerous and radicular cysts, whereas odontogenic keratocysts were completely negative (P < 0.002).

Conclusion: Immunohistochemical detection of CK 17 and 19 seems to be a valuable additional parameter distinguishing between odontogenic keratocysts and other odontogenic--especially dentigerous--cysts which clinically are likely the most significant differential diagnoses in this context. J Oral Pathol Med (2005) 34: 558-64.
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http://dx.doi.org/10.1111/j.1600-0714.2005.00352.xDOI Listing
October 2005

Vascular changes in the periosteum of congenital pseudarthrosis of the tibia.

Pathol Res Pract 2005 ;201(4):305-12

Institute of Pathology, University Hospital, RWTH Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany.

The etiology and the pathogenesis of congenital pseudarthrosis of the tibia (CPT) are still unknown. The affected tibia exhibits insufficient mechanical strength and osteogenetic capability. CPT is frequently associated with neurofibromatosis type 1 (NF1; von Recklinghausen's disease); however, both diseases have not yet been linked pathogenetically. This study presents the pathomorphologic findings of CPT under special consideration of NF1. Therefore, samples from patients operated on for CPT (n = 4) with (n = 3) and without (n = 1) neurofibromatosis were investigated by light microscopy, immunohistochemistry, and electron microscopy. The most striking finding in all patients was thickened periosteum with accumulation of nerval cells surrounding small arteries, causing subtotal or complete obliteration. In conclusion, impaired vascularization can result in decreased osteogenic capabilities. The similarity of ultrastructural findings in the abnormal periosteum and in skin neurofibromas of neurofibromatosis patients may indicate a pathogenetic association of both diseases.
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http://dx.doi.org/10.1016/j.prp.2004.09.013DOI Listing
August 2005

Concerted upregulation of CLP36 and smooth muscle actin protein expression in human endometrium during decidualization.

Cells Tissues Organs 2005 ;179(3):109-14

Department of Obstetrics and Gynecology, University Hospital RWTH Aachen, Aachen, Germany.

The human endometrium prepares for implantation of the blastocyst by reorganization of its whole cellular network. Endometrial stroma cells change their phenotype starting around the 23rd day of the menstrual cycle. These predecidual stroma cells first appear next to spiral arteries, and after implantation these cells further differentiate into decidual stroma cells. The phenotypical changes in these cells during decidualization are characterized by distinct changes in the actin filaments and filament-related proteins such as alpha-actinin. The carboxy-terminal LIM domain protein with a molecular weight of 36 kDa (CLP36) is a cytoskeletal component that has been shown to associate with contractile actin filaments and to bind to alpha-actinin supporting a role for CLP36 in cytoskeletal reorganization and signal transduction by binding to signaling proteins. The expression patterns of CLP36, alpha-actinin and actin were studied in endometrial stroma cells from different stages of the menstrual cycle and in decidual stroma cells from the 6th week of gestation until the end of pregnancy. During the menstrual cycle, CLP36 is only expressed in the luminal and glandular epithelium but not in endometrial stroma cells. During decidualization and throughout pregnancy, a parallel upregulation of CLP36 and smooth muscle actin, an early marker of decidualization in the baboon, was observed in endometrial decidual cells. Since both proteins maintain a high expression level throughout pregnancy, a role of both proteins is suggested in the stabilization of the cytoskeleton of these cells that come into close contact with invading trophoblast cells.
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http://dx.doi.org/10.1159/000085002DOI Listing
July 2006

Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis.

Breast Cancer Res Treat 2005 Mar;90(1):15-23

Department of Anatomy and Reproductive Biology, RWTH University of Aachen, Germany.

Impaired histone acetylation was recognized to be involved in carcinogenesis. Furthermore, histone deacetylase (HDAC) inhibitors induce differentiation of breast cancer cells and inhibit tumour growth. These results prompted us to study HDAC-1 and -3 expression in breast tumours to establish their potential therapeutic and prognostic significance. HDAC-1 und HDAC-3 protein expression was analyzed immunohistochemically on a tissue microarray (TMA) containing 600 core biopsies from 200 patients. HDAC-1 and -3 expression was correlated to steroid hormone receptor-, Her2/neu- and proliferation status of tumours as well as to overall and disease free survival. Moderate or strong nuclear immunoreactivity for HDAC-1 was observed in 39.8% and for HDAC-3 in 43.9% of breast carcinomas. HDAC-1 and -3 expression correlated significantly with oestrogen and progesterone receptor expression (both p< 0.001). HDAC-1 expression predicted significantly better disease free survival (DFS: p=0.044), in particular, in patients with small tumours of all differentiation types (DFS: p=0.016). Multivariate analysis demonstrated that HDAC-1 is an independent prognostic marker. Our data suggest that evaluation of HDAC-1 protein expression enables a more precise assessment of the prognosis of breast cancer patients. Thus, HDAC-1 expression analysis might be clinically useful to facilitate an individual, risk-directed, adjuvant systemic therapy in breast cancer patients.
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http://dx.doi.org/10.1007/s10549-004-1668-2DOI Listing
March 2005

TV-image analysis based quantification of the proliferative activity and the apoptotic rate in thyroid tumors and thyroiditis.

Anticancer Res 2003 Sep-Oct;23(5b):4269-75

Institute of Pathology, University of Aachen, Langenbeckstr. 1, D-55131 Mainz, Germany.

To analyze the impact of cellular proliferative activity and apoptosis, MIB-1 immunopositivity and the apoptotic rate of normal tissue (n = 20), follicular adenoma (n = 30), follicular carcinoma (n = 32), papillary carcinoma (n = 40), Hashimoto thyroiditis (n = 17) and de Quervain thyroiditis (n = 12) was investigated by means of TV-image analysis. Three-micron sections from paraffin-embedded surgical specimens were investigated. Immunohistochemical reactions were performed using an indirect peroxidase method. For determination of apoptosis the in situ DNA nick-end labeling method (TUNEL) was used. The rate of positive cells was determined using the CM-2 TV-image analysis system (Hund, Wetzlar, Federal Republic of Germany). Forty viewing fields (1.94 mm2) were measured with 20:1 objective mangnification. An average of > 4,400 cells were assessed in each case. The mean MIB-1 immunopositivity was higher in follicular carcinoma (average, 2.30%) than in de Quervain thyroiditis (1.48%), papillary carcinoma (1.26%), Hashimoto thyroiditis (0.97%), follicular adenoma (0.58%) and normal thyroid tissue (0.14%). The apoptotic rates were higher in Hashimoto thyroiditis (4.54%) and de Quervain thyroiditis (3.55%) than in thyroid tumors (0.31%-0.49%) and normal thyroid tissue (0.10%). Calculating the ratio of MIB-1 expression and apoptotic rate, thyroid tumors (12.1-14.6) revealed higher values than normal thyroid tissue (3.6), indicating cell gain. In Hashimoto thyroiditis (1.7) and de Quervain thyroiditis (0.7) the ratio was lower than in normal tissue indicating cell loss. MIB-1 immunohistometry and apoptotic rate quantification present new insights into the proliferative and apoptotic potential of thyroid lesions based on a high number of cells investigated per case. The impact of both methods could be used for the interpretation of diagnostically difficult and inconclusive fine-needle aspirates. However, as there was an overlap of the single values, the results have to be interpreted carefully for diagnostic purposes.
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December 2003