Chromosomal and DNA patterns in transitional cell bladder carcinoma: A comparative cytogenetic and flow-cytofluorometric DNA study

Abstract

Biopsy tissue from 71 bladder tumors in 57 patients was studied by chromosome analysis and flow cytofluorometry. Chromosome analysis was hampered by preparation difficulties and was successful in only 53% of the analyzed tumors. DNA analysis failed to reveal near‐diploid deviations, while the grossly aneuploid tumors generally had DNA values 10% to 15% above the numerical chromosome counts. Noninvasive tumors were diploid‐near‐diploid with occasional markers. Superficially invasive tumors were both diploid‐near‐diploid and near‐tetraploid, but with a chromosome count of only 80 in the latter cases. Deeply invasive tumors tended to be triploid on DNA analysis, and had chromosome counts in the vicinity of 60. In addition to single chromosome abnormalities, increased malignancy apparently is also associated with an increased total number of chromosomes. A tetraploid DNA level seems to represent a more stable genome, although chromosomes show gross abnormalities including markers.

Origins and clinical implications of aneuploidy in early bladder cancer

“…1C and associated discussion). This is in agreement with published cytogenetic studies in which early bladder cancers almost invariably exhibit some structural chromosomal changes and/or minor numerical chromosomal abnormalities ( 19,23,29,35). These early cytogenetic changes in bladder cancer and other solid tumors are expected to produce such small changes in overall cell DNA content that they are likely to be underreported by flow cytometric techniques (19,2435).…”

“…Nonetheless, much has been learned from cytogenetic and flow cytometric studies in which single tumor samples collected from large numbers of patients were grouped by clinicopathologic stage or histologic grade for comparison. In superficial bladder cancer, the development of gross numerical chromosomal abnormalities has been correlated with advancing histologic grade and/or clinicopathologic stage and with a poor clinical prognosis (9,19,23,35). Flow cytometric studies have highlighted the fact that the presence of multiple aneuploid peaks and the presence of hypertetraploidy are especially grave prognostic factors Neither the mechanism by which hypertetraploidy arises, nor the genetic basis for its adverse prognostic implications have been well understood.…”

Elevated levels of tetraploid cervical cells in human papillomavirus-positive Papanicolaou smears diagnosed as atypical squamous cells of undetermined significance

“…Tetraploidy has been observed consistently in human solid tumors of the breast, 43 ovaries, 44 bladder, 45 and esophagus. 46 In addition, it has been hypothesized that the aneuploidy characteristic of other human solid tumors occurs by chromosome loss from a transient tetraploid intermediate.…”

“…For PCR, the MY09 and MY11 primers were used to amplify HPV DNA, and the GH20 and PC04 primers were used to amplify human ␤-globin DNA (Qiagen, La Jolla, CA). Amplification of the L1 gene can allow for the identification of at least 20 HPV types (types 6,11,16,18,26,31,33,35,39,40,42,45,51,52,53,54,55,56,57, and 59). The DNA samples were extracted and purified for PCR using a proteinase K-phenol/chloroform procedure.…”

“…HPV analysis using the Digene HC II system was conducted at the commercial laboratory using at least 4 mL of cells suspended in the PreservaCyt solution. The HC II test can be used to detect HPV DNA from at least 13 different HPV types (types 16,18,31,33,35,39,45,51,52,56,58,59, and 68).…”