TY - JOUR A1 - Fischer, Uta A1 - Raptis, Georgios A1 - Horn, Lars-Christian T1 - Bedeutung der Familienanamnese bei Zervixkarzinom JF - Zentralblatt für Gynäkologie N2 - Fragestellung: Molekulare Analysen haben deutlich gemacht, dass maligne Tumoren durch Veränderungen des Genoms hervorgerufen werden. Im Gegensatz zu den erblich bedingten Tumorerkrankungen sind die Kenntnisse zur Bedeutung familiärer Faktoren bei den sog. sporadischen Tumoren, insbesondere beim Zervixkarzinom (CX) begrenzt. Material und Methode: Patientinnen des CX-Registers der Universitäts-Frauenklinik wurden retrospektiv bezüglich der Familienanamnese (FA) analysiert. Als positive FA wurde eine maligne Tumorerkrankung bei einem oder mehreren Verwandten ersten Grades definiert. Es wurde unterschieden, ob es sich um Zervixkarzinome, andere gynäkologische Malignome (außer Mammakarzinom) oder eine extragenitale Lokalisation handelte. Diese Daten wurden zum Erkrankungsalter und zum Nachweis pelviner Lymphknotenmetastasen in Beziehung gesetzt. Ergebnisse: 159/737 Frauen (21,6 %) wiesen eine positive FA auf. In 10,7 % der Fälle war mehr als ein Verwandter ersten Grades erkrankt; bei 6,9 % Angehörige ersten und zweiten Grades. Weibliche Verwandte ersten Grades von 42 Frauen wiesen Malignome des weiblichen Genitaltraktes (außer CX) auf. In 6,9 % waren die Mutter und/oder die Schwester an einem Zervixkarzinom erkrankt. Das Durchschnittsalter der Patientinnen mit positiver Familienanamnese (FA) unterschied sich nicht von dem derjenigen mit leerer FA, wohl aber bei getrennter Betrachtung nach der Tumorlokalisation. Bezüglich des Tumorstadiums (pTNM) und der Zahl der Patientinnen mit histologisch nachgewiesenen pelvinen Lymphknotenmetastasen bestand kein Unterschied. Schlussfolgerungen: Die bisherigen Ergebnisse deuten auch beim Zervixkarzinom auf eine familiäre Belastung hin. Dabei existieren offenbar Familien, in denen mit HPV-assoziierte Präkanzerosen bzw. Tumoren vermehrt auftreten. Besonders gefährdet sind Patientinnen, deren weibliche Anverwandte ersten Grades bereits an einer zervikalen Präkanzerose (besonders CIN III) oder einem invasiven CX erkrankt sind. Diese Frauen sollten einem engmaschigen Screening unterzogen werden. T2 - Impact of familiar history in cervical cancer patients KW - Gebärmutterhalskrebs KW - Familienanamnese KW - Zervixkarzinom KW - hereditär KW - familiär KW - Anamnese KW - Karzinom KW - Prognose Y1 - 2001 U6 - https://doi.org/10.1055/s-2001-14791 VL - 123 SP - 302 EP - 307 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Fischer, Uta A1 - Raptis, Georgios A1 - Bilek, Karin A1 - Hentschel, Bettina A1 - Richter, Christine E. A1 - Braumann, Ulf Dietrich A1 - Einenkel, Jens T1 - Pattern of invasion is of prognostic value in surgically treated cervical cancer patients JF - Gynecologic Oncology N2 - Objectives: Different patterns of invasion (representing different grades of tumor cell dissociation) are associated with prognostic outcome in cancer. We evaluated the prognostic value of different patterns of invasion (PI) in cervical carcinomas (CX). Methods: Six hundred eleven surgically treated CX (FIGO IB to IIB) were re-evaluated histologically regarding the PI, using a three-level scoring system. Closed PI was defined as cohesive growth with well-delineated (pushing) borders. In finger-like PI the tumor grows in solid cords/trabecles. Highly dissociative growth in small groups or single cells was defined as spray-like PI. Types of PI were correlated to tumor stage, histo-morphologic factors and prognostic outcome. Results: Sixty percent of the tumors showed a spray-like PI, 30% a finger-like PI and only 7.4% were of the closed type. Spray-like PI showed a significant correlation with advanced stage disease, lymphovascular space involvement, poorly differentiated tumors and pelvic lymph node metastases. Spray-like PI was accompanied by a reduced 5-year overall survival when compared to the finger-like and closed PI (68.7% vs. 80.9% vs. 88.5%; P=0.0004). The prognostic impact of the PI disappeared in node-positive patients (P=0.06) but persisted in patients without pelvic lymph node disease (P=0.03). In multivariate analysis, using COX regression model, the PI represented as independent prognostic factor. Conclusions: Spray-like PI (i.e., highest degree of tumor cell dissociation) is associated with advanced tumor stages, increased rate of recurrency and a reduced overall survival. In separate analysis of patients with and without lymph node metastases, the impact of PI persisted only in node-negative cases as a prognostic factor. KW - Gebärmutterhalskrebs KW - Chirurgie KW - Metastase Y1 - 2006 U6 - https://doi.org/10.1016/j.ygyno.2006.05.046 VL - 103 IS - 3 SP - 906 EP - 911 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Fischer, Uta A1 - Hentschel, Bettina A1 - Köhler, U. A1 - Richter, Christine E. A1 - Martin, Rosemarie T1 - CD44-v6 concentrations in carcinoma of the uterine cervix: lack of prognostic significance JF - Archives of Gynecology and Obstetrics N2 - Several kinds of cellular adhesion molecules, like different splicing variants of CD 44, have gained important as prognostic or markers for metastatic disease. Fresh frozen samples from 64 cervical carcinoma (CX) were stored in liquid nitrogen and examined using ELISA-technique, testing the prognostic impact. Normal cervical tissue served as control. CD 44-v6 concentration, was significant elevated in tumor tissue, when compared to the controls (P=0.04). There was no correlation to tumor stage (P=0.61), lymphovascular space involvement (P=0.075) or pelvic lymph node involvement (P=0.81). The CD 44-v6 concentration was not informative regarding recurrence-free and overall survival. Contrary to immunohistochemistry, the quantification of CD 44-v6 using ELISA-technique does not provide any further information. KW - Gebärmutterhalskrebs KW - Antigen CD44 Y1 - 2005 U6 - https://doi.org/10.1007/s00404-005-0039-5 VL - 273 IS - 2 SP - 104 EP - 106 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Fischer, Uta A1 - Bilek, Karin T1 - Standardised handling of hysterectomy specimen in cervical cancer – report of over 900 stage pT1b1- to pT2b-tumors JF - Pathology - Research and Practice KW - Gebärmutterhalskrebs KW - Chirurgie KW - Gewebe KW - Gebärmutterentfernung Y1 - 2000 VL - 196 SP - 450 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Martin, Rosemarie T1 - Tumorassoziierte Proteolyse, p53-Immunhistochemie und Zelladhäsion bei primär operierten Zervixkarzinomen JF - Geburtshilfe und Frauenheilkunde KW - Tumorassoziierte Proteolyse KW - Immuncytochemie KW - Zelladhäsion KW - Gebärmutterhalskrebs Y1 - 2000 VL - 60 IS - Suppl. 1 SP - 200 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Fischer, Uta A1 - Tannapfel, A. A1 - Kuhn, H. A1 - Hänel, C. A1 - Raptis, Georgios T1 - The role of p53 tumorsuppressorgene in tumor progression in cervical cancer JF - Pathology - Research and Practice KW - Tumorsuppressor-Gen KW - Tumorwachstum KW - Gebärmutterhalskrebs Y1 - 1999 VL - 195 SP - 328 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Nenning, Hans T1 - DNA cytometric analysis of surgically treated squamous cell cancer of the uterine cervix, stage pT1b1-pT2b JF - Analytical and quantitative cytology and histology N2 - Objective: To determine the utility of DNA content and DNA-related variables of proliferative activity regarding prognosis in cervical cancer. Study design: DNA image (ICM) andflow cytometry (FCM) were performed to determine the DNA index (DI), 5c-exceeding rate (5c-ER), S-phase fraction (SPF) and proliferation index (PI) in 163 patients with surgically staged pT1b1-pT2b squamous cell cancer of the uterine cervix and treated with primary radical hysterectomy. ICM was performed on imprint cytology, obtained from fresh tumor tissue, which was also used for FCM. Results were analyzed using the chi2 test and Cox regression analysis for risk of pelvic lymph node involvement, tumor recurrence and recurrence-free survival (RFS). Results: ICM was performed on all 163 and FCM on 133 samples. One-third of the tumors showed DNA aneuploidy. Analysis demonstrated prognostic significance of a DI > or = 1.70, with a (70:30) 2.3-fold risk of recurrence (P=.024) and reduced RFS of 10 months (P=.003) in cases of DI > or = 1.70. A high 5c-ER > 11% was associated with pelvic lymph node involvement and decreased RFS (P < or = .04). Significantly more relapses were found in tumors with SPF > 12% (70.8% vs. 29.2%, P=.007). RFS was markedly reduced in tumors with high SPF (52.3 vs. 61.1 months, P=.011). Low proliferative tumors (PI<25%) were associated with lower stage (P=.036) and increased RFS (61.2 vs. 47.1 months, P=.028). In multivariate analysis of clinicopathologic variables (pT category, nodal status, lymphovascular space involvement) and DNA related variables, pelvic lymph node involvement was the only significant predictor of RFS. In patients with nodal involvement, tumors with DI >1.70 were associated with lessfavorable outcomes. Conclusion: DNA-related variables of cell cycle analysis were valuablefor predicting prognosis in cervical cancer patients. Tumors with DI>1.70, 5c-ER >11% and high proliferative activity (SPF>12%, PI>25%) represent a subgroup with a poor prognosis. KW - Gebärmutterhals KW - squamöser Krebs KW - Cytometrie KW - Chirurgie Y1 - 2002 VL - 24 IS - 1 SP - 23 EP - 29 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Pippig, S. A1 - Raptis, Georgios A1 - Fischer, Uta A1 - Köhler, U. A1 - Hentschel, Bettina A1 - Martin, Rosemarie T1 - Clinical relevance of urokinase-type plasminogen activator and its inhibitor type-1 (PAI-1) in squamous cell carcinoma of the uterine cervix JF - Australian and New Zealand Journal of Obstetrics and Gynaecology N2 - Objective The expression of uPA and PAI‐1 as parameters of tumour‐associated proteolysis has been implicated in the process of tumour cell invasion and the metastatic process. However, there is limited information on the impact of these parameters in cervical carcinoma. Methods Quantitative levels for uPA (n = 114) and PAI‐1 (n = 103) were researched in operatively treated, surgically staged squamous cell cancer of the uterine cervix, using an ELISA‐technique. Results were assessed regarding their impact in predicting pelvic lymph nodes metastases, tumour recurrence rate and recurrence free survival (RFS) using uni‐ and multivariate analysis. Results Median levels of both parameters were significantly higher in tumour tissue than in normal cervical tissue (p < 0.001). Detection of uPA gave no useful prognostic information. PAI‐1 concentration showed a positive correlation with advanced tumour stage (p = 0.008), but no significant correlation with nodal status (pN0: 2.6 vs. pN1: 4.0 ng/mg protein; p = 0.092). Using a cut‐off level of 2.4 ng/mg protein, patients with elevated PAI‐1 levels demonstrated reduced RFS (45.9 versus 52.9 months; p = 0.1). Multivariate analysis, including nodal status, tumour stage, lymphovascular space involvement and grading failed to demonstrate any prognostic impact of uPA and PAI‐1. Conclusions The results indicate, that PAI‐1 expression is of some prognostic impact in cervical cancer, indicating an association of elevated PAI levels with local tumour progression and reduced recurrence‐free survival. KW - Plasminogen human-Aktivator KW - Urokinase KW - squamöser Krebs KW - Gebärmutterhals Y1 - 2004 U6 - https://doi.org/10.1111/j.0004-8666.2002.00385.x VL - 42 IS - 4 SP - 385 EP - 388 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Fischer, Uta A1 - Raptis, Georgios A1 - Bilek, Karin A1 - Hentschel, Bettina T1 - Tumor size is of prognostic value in surgically treated FIGO stage II cervical cancer JF - Gynecologic Oncology N2 - Objectives Tumor size is a well recognized prognostic factor in early stage cervical carcinoma (CX). However, limited knowledge exists about the value of tumor size in surgically treated CX with extrauterine extension. Methods 245 cases of local advanced CX (FIGO stage IIA and IIB) who received upfront surgery were evaluated regarding tumor size, regarding the prediction of pelvic lymph node involvement and recurrence free and overall survival during a median follow-up time of 54 months (95% CI 45.4–62.6 months). Tumors larger than 4 cm were defined as bulky stage disease. Results Bulky disease was seen in 46.1% (113/245). 60.2% of these patients showed pelvic lymph node involvement, compared to 42.4% (56/132) in non-bulky tumors (p = 0.006; odds ratio: 2.2 [95% CI: 1.3–3.6]). Patients with bulky tumors showed an increase of recurrent disease (40.2% vs. 28.0%; p = 0.045). The relative risk for recurrent disease was 1.97 (95% CI: 1.3–3.0). The 5-year overall survival rate was significantly lower (67.7% [95% CI: 58.2–74.8] vs. 49.5% [95% CI: 36.8–59.1]; p = 0.0015). In multivariate analysis, tumor stage, pelvic lymph node involvement and maximal tumor size were independent prognostic factors. Conclusions The results suggest that tumor size, defining bulky disease as tumors larger than 4 cm, is of prognostic impact also in FIGO stage II cervical carcinomas. A revised FIGO/TNM classification system similar to the subgrouping of stage IB CX is recommended for stage II using a cut-off value of 4 cm as discriminator: stage IIA1 and stage IIB1 for tumors with ≤ 4 cm and IIA2 and IIB2 for tumors > 4 cm (i.e. bulky disease). KW - Gebärmutterhalskrebs KW - Chirurgie KW - Tumorwachstum Y1 - 2007 U6 - https://doi.org/10.1016/j.ygyno.2007.06.026 VL - 107 IS - 2 SP - 310 EP - 315 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Fischer, Uta A1 - Bilek, Karin T1 - Impact of tumorload in surgically treated, histologically staged early cervical cancer: Multivariate analysis of 568 patients JF - International Journal of Gynecology & Obstetrics KW - Gebärmutterhalskrebs KW - Chirurgie KW - Tumorklasifikation Y1 - 2000 VL - 70 IS - Suppl. 1 SP - 20 EP - 21 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Fischer, Uta A1 - Bilek, Karin T1 - p53-tumorsuppressor gene in surgically treated histologically staged early cervical cancer JF - International Journal of Gynecology & Obstetrics KW - Tumorsuppressor-Gen KW - Chirurgie KW - Histopathologie KW - Gebärmutterhalskrebs Y1 - 2000 VL - 70 IS - Suppl. 1 SP - 112 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Fischer, Uta A1 - Hanel, C. A1 - Kuhn, H. A1 - Raptis, Georgios A1 - Bilek, Karin T1 - p53 in surgically treated and pathologically staged cervical cancer BT - correlation with local tumor progression, but not with lymphatic spread JF - Pathology - Research and Practice KW - Gebärmutterhalskrebs KW - Tumorsuppressor-Gen KW - Chirurgie KW - Histopathologie Y1 - 2001 VL - 197 IS - 9 SP - 605 EP - 609 ER - TY - CHAP A1 - Horn, Lars-Christian A1 - Pippig, S. A1 - Raptis, Georgios A1 - Fischer, Uta A1 - Köhler, U. A1 - Hentschel, Bettina A1 - Martin, Rosemarie T1 - Tumorassoziierte Proteolyse beim Zervixkarzinom BT - Vortrag T2 - 87. Tagung der Deutschen Gesellschaft für Pathologie, 14. Juni 2003 KW - Gebärmutterhalskrebs KW - Chirurgie KW - Tumorassoziierte Proteolyse KW - Immuncytochemie KW - Zelladhäsion Y1 - 2003 ER - TY - JOUR A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Fischer, Uta T1 - Familial cancer history in patients with carcinoma of the cervix uteri JF - European Journal of Obstetrics & Gynecology and Reproductive Biology KW - Gebärmutterhalskrebs KW - Familienanamnese Y1 - 2002 U6 - https://doi.org/10.1016/s0301-2115(01)00520-6 VL - 101 IS - 1 SP - 54 EP - 57 ER - TY - JOUR A1 - Fischer, Uta A1 - Raptis, Georgios A1 - Geßner, W. A1 - Roschlau, U. A1 - Dressel, K. A1 - Bilek, Karin A1 - Horn, Lars-Christian T1 - Epidemiologie und formale Pathogenese des Zervixkarzinoms JF - Zentralblatt für Gynäkologie T2 - Epidemiology and pathogenesis of cervical cancer KW - Gebärmutterhalskrebs KW - Epidemiologie KW - Pathogenese Y1 - 2001 VL - 123 IS - 4 SP - 198 EP - 205 ER - TY - GEN A1 - Horn, Lars-Christian A1 - Raptis, Georgios A1 - Fischer, Uta T1 - Familiäres Zervixkarzinom – Erste Ergebnisse BT - Poster T2 - 54. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe KW - Gebärmutterhalskrebs KW - Familienanamnese Y1 - 2002 ER -