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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.
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.
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.
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).