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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.
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.
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.
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.