Zusammenfassung
Fragestellung
Zervixkarzinome sind meistens Plattenepithelkarzinome, während Adenokarzinome seltener
auftreten. Spezifische genomische Veränderungen sind verantwortlich für die Karzinogenese
und Tumorprogression von Zervixkarzinomen. Der Zusammenhang zwischen Genotyp und Phänotyp
beim Zervixkarzinom ist bis heute unklar.
Material und Methodik
Die Methode der Comparative Genomic Hybridization wurde verwendet, um in 62 Plattenepithel-
und 22 Adenokarzinomen des klinischen Stadiums FIGO IB nach DNS-Sequenzveränderungen
zu suchen. Zusätzlich wurde der HercepTestTM angewandt, um immunhistochemisch die Expression von HER-2/neu beim Adenokarzinom
zu beurteilen.
Ergebnisse
In beiden Tumorarten waren DNS-Sequenzverluste am häufigsten auf 4 q, Xq und 18 q
zu finden. DNS-Sequenzverluste waren die häufigsten Alterationen beim Plattenepithelkarzinom,
während DNS-Sequenzvermehrungen auf 17 q die häufigste Alteration beim Adenokarzinom
darstellten. HER-2/neu Überexpression wurde nur in 2 Adenokarzinomen festgestellt.
Die Gesamtzahl der DNS-Aberrationen pro Tumor und die Anzahl von DNS-Sequenzverlusten
pro Tumor waren signifikant assoziiert mit dem tumorspezifischen Überleben beim Plattenepithelkarzinom.
Sequenzverluste auf den Chromosomen 11 p und 18 q waren signifikant assoziiert mit
einer schlechten Prognose beim Plattenepithelkarzinom ohne Lymphknotenmetastasen.
Analog zum Plattenepithelkarzinom sind DNS-Sequenzverluste des Chromosoms 18 q auch
beim Adenokarzinom eindeutig assoziiert mit einer schlechten Prognose.
Schlussfolgerung
DNS-Sequenzvermehrungen auf 17 q sind nicht mit einer HER-2 Überexpression beim Adenokarzinom
verbunden. Die Inaktivierung von Tumorsuppressor-Genen auf 18 q ist offenbar verantwortlich
für die Tumorprogression sowohl des Adeno- als auch des Plattenepithelkarzinoms der
Cervix uteri.
Abstract
Purpose
Cervical carcinomas are almost always squamous cell carcinomas, whereas adenocarcinomas
are rare. There is evidence that specific genetic events are involved in initiation
and progression of invasive cervical cancer. The genotype-phenotype correlations in
cervical cancer are unclear.
Material and Methods
Comparative genomic hybridization was applied to screen for DNA copy number changes
in 62 squamous cell carcinomas and 22 adenocarcinomas of clinical stage IB. Immunohistochemistry
was performed in adenocarcinoma samples to determine the HER-2 expression (HercepTestTM).
Results
In both cancer types, DNA sequence losses were most prevalent at chromosomes 4 q,
Xq and 18 q. Losses were the most frequent alterations in squamous cell carcinoma,
whereas DNA sequence gains of chromosome 17 q (54 %) represented the most frequent
copy number alterations in cervical adenocarcinomas. HER-2 overexpression was detected
in only two adenocarcinomas. The total number of DNA aberrations per tumor (P < 0.02),
and the number of DNA sequence losses per tumor (P < 0.04) were associated with disease-specific
survival in squamous cell carcinoma. 9 p deletions were significantly more frequent
in squamous cell carcinomas with lymph node metastasis than in node negative tumors
(P < 0.03). Losses of chromosome 11 p (P < 0.0001) and 18 q (P < 0.01) were associated
with poor prognosis in squamous cell carcinomas without lymph node metastasis. In
analogy to squamous cell carcinoma, DNA sequence losses of chromosome 18 q were significantly
associated with poor prognosis in cervical adenocarcinoma (P < 0.01).
Conclusion
DNA sequence copy number gains on 17 q are not associated with HER-2 expression in
adenocarcinomas. The inactivation of tumor suppressor genes on chromosome 18 q might
be responsible for the progression of both cervical adenocarcinoma and squamous cell
carcinoma.
Schlüsselwörter
Zervixkarzinom - Genomische Aberrationen - Chromosom 11 p - Chromosom 18 q - CGH
Key words
Cervical cancer - Genomic aberrations - Chromosome 11 p - Chromosome 18 q - CGH
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PD Dr. med. Athanassios Dellas
Oberer Batterieweg 39
4059 Basel
Schweiz
eMail: a.dellas@unibas.ch
