Complex karyotypes in flow cytometrically DNA-diploid squamous cell carcinomas of the head and neck

Åkervall, Jan; Jin, Yuesheng; Baldetorp, Bo; Mertens, Fredrik; Wennerberg, Johan

doi:10.1038/bjc.1998.180

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…However, monosomies in DNA-diploid tumours expose a flagrant disagreement between FCM and FISH data. Also by metaphase analysis, seemingly diploid head and neck carcinomas have occasionally been demonstrated to exhibit karyotypic aberrations [21]. It would therefore be reasonable to speculate that diploidy by FCM simply reflects methodical limitations to resolve clones with minor DNA content aberrations from non-malignant cellular components.…”

Section: Discussionmentioning

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

Hemmer

Hauser

2000

Analytical Cellular Pathology

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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.

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Section: Discussionmentioning

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

Hemmer

Hauser

2000

Analytical Cellular Pathology

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“…Perhaps, the notably reduced mitotic activity in lichen sclerosis may relate to a loss of DNA, as reflected by hypodiploidy in our study. Further studies on the chromosomes and genes of lichen sclerosis are indicated, as ploidy is only a rough guide to what is happening in the nucleus and significantly understates chromosomal changes ( 29 ) .…”

Section: Discussionmentioning

confidence: 99%

Ploidy in human papillomavirus positive and negative vulvar squamous cell carcinomas and adjacent skin lesions

Scurry

Hung

Flowers³

et al. 1999

Int J Gynecol Cancer

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To better characterize the two clinicopathologic types of squamous cell carcinoma, human papillomavirus (HPV) positive and negative, and their adjacent skin changes, we performed cytomorphometric analysis on 12 HPV-positive squamous cell carcinomas and adjacent vulvar intraepithelial neoplasia and 22 HPV-negative squamous cell carcinomas and adjacent squamous cell hyperplasia and lichen sclerosis. Our results were that 83% (10 of 12) HPV-positive carcinomas and 78% (7 of 9) adjacent vulvar intraepithelial neoplasia were aneuploid, compared with 59% (13 of 22) HPV-negative carcinomas, 6% (1 of 16) squamous cell hyperplasias and 0% (0 of 20) lichen scleroses. Seventy-five percent (9 of 12) HPV carcinomas and 78% (7 of 9) vulvar intraepithelial neoplasias showed two aneuploid peaks, but no HPV-negative carcinoma or non-neoplastic epithelial lesion showed multiple aneuploid peaks. Fifty percent of squamous cell hyperplasias (8 of 16) and lichen scleroses (10 of 20) adjacent to HPV-negative carcinomas were hypodiploid. The mean DNA indices were: 1.70 for the dominant tumor cell population of HPV-positive carcinoma, 1.64 for the dominant population of vulvar intraepithelial intraepithelial neoplasia, 1.41 for HPV-negative carcinoma, 0.85 for squamous cell hyperplasia and 0.83 for lichen sclerosis. In conclusion, the higher rate of aneuploidy, higher mean DNA index, and presence of multiploid peaks in HPV-positive carcinomas and adjacent vulvar intraepithelial neoplasias compared with the lower rate of aneuploidy, lower mean DNA index, absence of multiploid peaks of HPV-negative carcinomas and tendency to hypodiploidy in squamous cell hyperplasia and lichen sclerosis support the hypothesis that there are two clinicopathologic types of vulvar carcinoma, with different pathogenetic mechanisms. The similarities in ploidy findings between vulvar HPV-positive carcinomas and vulvar intraepithelial neoplasia and those previously published for cervical carcinoma and cervical intraepithelial neoplasia support the view that these two cancers are analogous and have similar pathogenetic mechanisms. The frequent finding of hypodiploidy in squamous cell hyperplasia and lichen sclerosis next to HPV-negative carcinomas requires further investigation of the molecular pathogenesis of this cancer type.

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“…observations). It is also important to bear in mind that FCM is not likely to detect an aberrant cell population comprising less than 5% of the total cell population, and that FCM DNA diploid tumours can have cytogenetically complex cell populations not detected by FCM [19]. The finding that the CVs of the diploid peaks were higher than of the aneuploid indicates that the diploid peak harbours both normal diploid cells and diploid, or near-diploid, tumour cells that cannot be separated in the FCM histogram.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Non-Diploid Flow-Cytometric DNA Indices and Their Relation to the Nodal Metastasis in Squamous Cell Carcinomas of the Head and Neck

Wennerberg

Baldetorp²,

Wahlberg³

1998

Invasion Metastasis

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Squamous cell carcinomas of the head and neck (HNSCC) evolve from diploid epithelial cells of the mucosa. At the time of diagnosis about two thirds of clinically diagnosed HNSCC are non-diploid according to flow-cytometric (FCM) analysis, indicating that during tumour progression there must be an acquisition and accumulation of chromosomal aberrations. At diagnosis one third to one half of HNSCC have clinically positive neck nodes. The objective of the present study was to see whether the progression to a metastatic phenotype is reflected in the distribution of FCM DNA ploidy in node-negative and node-positive HNSCC. The series comprised 200 patients with HNSCC. Tumour samples were obtained from diagnostic biopsies or primary surgery. A multistep preparation method and propidium iodide staining of nuclear DNA content was used for FCM. One hundred and forty one (71%) of the tumours were non-diploid. Only two tumours were hypodiploid (DNA index 0.73 and 0.93, respectively). Ten of the tumours exhibited two non-diploid stem cell lines. The frequency of non-diploidy in node-negative tumours was 65% and in node-positive ones about 80%. The frequency distribution of non-diploid DNA indices clustered in the hypotetraploid region (with a modal value of 1.71–1.74) and did not differ between node-negative and node-positive tumours. The hypothesis that the disposition to metastasis is reflected in the frequency distribution of non-diploid DNA indices could thus not be verified.

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Complex karyotypes in flow cytometrically DNA-diploid squamous cell carcinomas of the head and neck

Cited by 7 publications

References 24 publications

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

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

Ploidy in human papillomavirus positive and negative vulvar squamous cell carcinomas and adjacent skin lesions

Distribution of Non-Diploid Flow-Cytometric DNA Indices and Their Relation to the Nodal Metastasis in Squamous Cell Carcinomas of the Head and Neck

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