Flow Cytometric Cellular Dna Content and Lymph-Node Metastasis in Squamous-Cell Carcinoma of the Oral Cavity

Analytical Cellular Pathology

Hauser

2000

Studies with DNA flow cytometry (FCM) have shown that DNA contents of aneuploid tumour clones vary in a wide range. The aim of this study was to analyse whether homologous chromosomal changes exist despite the individual differences that may be of general relevance for the development of gross aneuploidy in squamous cell carcinomas of the head and neck. Fluorescence in situ hybridization (FISH) with 13 centromere‐specific DNA probes was applied to 3 diploid and 11 aneuploid tumours with DNA indices ranging between 0.8 and 2.2. Disomic and monosomic cell populations were prevalent findings in DNA‐diploid tumours. Polysomies were common in aneuploid tumours. Different degrees of aneusomy for identical chromosomes were recurrent features in aneuploid tumours. FISH signal heterogeneity was identified for all chromosomes. The mean number of aneusomic cell populations identified for DNA‐aneuploid tumours ranged between 1.6 for chromosome 17 and 3.1 for chromosome 3. Inconsistencies between FISH and FCM data may indicate that centromere‐specific DNA probes identify gains and losses of marker DNA due to complex karyotypic rearrangements rather than absolute changes in chromosome numbers. Overall, there was no evidence of the critical involvement of particular chromosomes in the development of different DNA contents.

Section: Introductionmentioning

confidence: 99%

Chromosomal Composition of Aneuploid Clones with Different DNA Contents in Head and Neck Squamous Cell Carcinomas as Determined by Combined Flow Cytometry and Fluorescence In Situ Hybridization

Analytical Cellular Pathology

Hauser

2000

“…Allerdings wurde in einigen Fällen Aneuploidie bei rezidivierten pleomorphen Adenomen dokumentiert [1,33,39]. Umfassende Untersuchungen an Plattenepithelkarzinomen der Mundhöhle haben nicht nur gezeigt, dass Patienten mit aneuploiden Tumoren ein gegenüber diploiden Fällen dramatisch erhöhtes Risiko einer lokalen und regionalen Rezidivierung tragen [18][19][20]24], sondern auch dass die aneuploiden Zellen selbst Träger des invasiven und metastasierenden Wachstums sind [21,26]. Ob ein solcher Zusammenhang auch für pleomorphe Adenome zutrifft, und gegebenenfalls auch für andere benigne Speicheldrüsentumoren, ist aufgrund der spärlichen Hinweise kaum abzuschätzen.…”

Section: Patienten Und Methodenunclassified

“…Mit dieser Methode konnte in umfangreichen Studien an oralen Plattenepithelkarzinomen eine Aneuploidierate von ungefähr 80% festgestellt werden, wobei sich der Ploidie-Status zudem als unabhängiger prognostischer Faktor für Überleben [18,24], regionale Metastasierung [19][20][21][22] und lokale Rezidivierung [20] erwies. Die bislang an Speicheldrüsentumoren durchgeführten Untersuchungen sind weit weniger aufschlussreich, was im Wesentlichen auf zwei Ursachen zurückgeführt werden kann: Sie beschränken sich meist auf eine geringe Fallzahl und die DNA-Analysen beruhen häufig auf der Verwendung von archiviertem Tumormaterial, womit in der Regel nur eine unzureichende Messpräzision erreicht werden kann.…”

Section: Introductionunclassified

DNA-Ploidie und proliferative Aktivität bei Speicheldrüsentumoren

Driemel

Kraft

Mund Kiefer GesichtsChir

2007

ZusammenfassungMithilfe hoch-auflösender DNA-Durchflusszytophotometrie wurden DNA-Ploidie und SPhasenfraktion (SPF) bei 279 Speicheldrüsentumoren bestimmt. Alle 229 benignen Neoplasien waren diploid; 12 von 50 malignen Tumoren wiesen Zellpopulationen mit aneuploidem DNA-Gehalt auf. Die SPF-Werte der diploiden Malignome waren signifikant höher als bei pleomorphen Adenomen, unterschieden sich jedoch nicht von denen der Zystadenolymphome (Warthin-Tumoren). Während Aneuploidie ein Malignitätsmerkmal darstellt, ist der SPF-Wert für die Dignitätsdiagnostik bei Speicheldrüsentumoren nur von eingeschränktem Nutzen.DNA ploidy and proliferative activity in salivary gland tumours Abstract DNA ploidy and S-Phase fraction (SPF) of 279 salivary gland tumours were analysed using high-resolution DNA flow cytometry. All 229 benign neoplasms were diploid while 12 of 50 malignant tumours showed cell populations with aneuploid DNA content. The SPF values of diploid malignancies were significantly higher if compared with pleomorphic adenomas but did not differ from that of the zystadenolymphoma (Warthin tumour) group. While aneuploidy represents a distinct indicator of malignancy SPF values are of minor relevance for dignity assessment in salivary gland tumours.(Vortrag gehalten bei der 36. Jahrestagung des Deutsch-Österreichisch-Schweizerischen Arbeitskreises für

“…Aneuploidy has actually turned out as an independent predictor of survival in oral squamous cell carcinoma (3)(4)(5)(6). The outcome of patients is essentially determined by a several-fold increase in risk of local and regional recurrence after the emergence of DNA-aneuploid cell populations (4,(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, although DNA contents vary in wide range, thus implying corresponding karyotypic disparities, neither the metastatic behaviour of tumours nor the outcome of patients correlate with the degree of aneuploidy (2,7). A conceivable explanation is that aneuploid clones, despite their overall differences in chromosomal composition, may share discrete karyotypic aberrations that are decisive for the expression of malignant behaviour.…”

Section: Introductionmentioning

confidence: 99%

Correlation between DNA ploidy by flow cytometry and chromosome 3 aberration in oral squamous cell carcinoma

Kraft²,

Heerden³

2006

Oncol Rep

Abstract. Although flow cytometric DNA ploidy has turned out as a significant predictor of survival in oral squamous cell carcinoma, little is known about the underlying karyotypic structure of gross aneuploidy. We therefore analysed one diploid and 9 aneuploid carcinomas with relative DNA contents between 1.1 and 2.8 by fluorescence in situ hybridization with topologic markers for the centromere (3cen) and the terminal regions (3p, 3q) of chromosome 3. Progressing deviation of aberrant DNA contents from the normal diploid value correlated with increasing 3cen copy numbers per cell. A pronounced marker heterogeneity suggested that DNA-aneuploid cell populations consisted of karyotypically different clones. Monosomy of 3p was the only chromosomal alteration in the DNA diploid tumour. A significant 3p underrepresentation was a recurrent finding also in 7 of 9 aneuploid carcinomas while a subset of cells in each of 2 other cases showed a complete loss of one sister chromosome 3. In contrast, 7 of 9 aneuploid tumours exposed corresponding 3q and 3cen copy numbers, 2 showed a substantial 3q overrepresentation. It appears that amplification of chromosome 3 plays a role in the development of aneuploidy and the concurrent overexpression of 3q target genes. Acquired loss of the short arm of chromosome 3 in DNA-diploid tumour cells may contribute to the manifestation of recurrent 3q deletions in aneuploid cell populations. IntroductionWhile a multistep carcinogenetic process, in which mutations of tumour suppressor genes and oncogenes may play a critical role, has been proposed for the development of oral squamous cell carcinoma (1), DNA flow cytometric studies provided evidence that gross karyotype rearrangements contribute to the acquisition of invasive and metastatic behaviour (2,3). Aneuploidy has actually turned out as an independent predictor of survival in oral squamous cell carcinoma (3-6). The outcome of patients is essentially determined by a several-fold increase in risk of local and regional recurrence after the emergence of DNA-aneuploid cell populations (4,6-9).DNA content aberrations signify a fundamental reorganisation of the tumour cell genome in which gains and losses of chromosomes substantially contribute to the expression of altered DNA contents (10). Remarkably, although DNA contents vary in wide range, thus implying corresponding karyotypic disparities, neither the metastatic behaviour of tumours nor the outcome of patients correlate with the degree of aneuploidy (2,7). A conceivable explanation is that aneuploid clones, despite their overall differences in chromosomal composition, may share discrete karyotypic aberrations that are decisive for the expression of malignant behaviour. As multiple studies suggested that mutations involving the short arm of chromosome 3 may be critical for the progression of squamous cell carcinomas of the head and neck (11-19), we analysed the pattern and frequency of rearrangements of chromosome 3 by fluorescence in situ hybridization in oral squamous cell carcinomas ...