scholarly journals Correlation of DNA Ploidy with Progression of Cervical Cancer

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
M. Singh ◽  
S. Mehrotra ◽  
N. Kalra ◽  
U. Singh ◽  
Y. Shukla

The majority of squamous cell carcinomas of cervix are preceded by visible changes in the cervix, most often detected by cervical smear. As cervical cancer is preceded by long precancerous stages, identification of the high-risk population through detection of DNA ploidy may be of importance in effective management of this disease. Here we attempted to correlate aneuploid DNA patterns and their influence on biological behavior of flow-cytometry analysis of DNA ploidy which was carried out in cytologically diagnosed cases of mild (79), moderate (36), and severe (12) dysplasia, as well as “atypical squamous cells of unknown significance (ASCUS)” (57) along with controls (69), in order to understand its importance in malignant progression of disease. Cytologically diagnosed dysplasias, which were employed for DNA ploidy studies, 39 mild, 28 moderate, and 11 severe dysplasia cases were found to be aneuploid. Out of the 69 control subjects, 6 cases showed aneuploidy pattern and the rest 63 subjects were diploid. An aneuploidy pattern was observed in 8 out of 57 cases of cytologically evaluated ASCUS. The results of the followup studies showed that aberrant DNA content reliably predicts the occurrence of squamous cell carcinoma in cervical smear. Flow cytometric analysis of DNA ploidy may provide a strategic diagnostic tool for early detection of carcinoma cervix. Therefore, it is a concept of an HPV screening with reflex cytology in combination with DNA flow cytometry to detect progressive lesions with the greatest possible sensitivity and specificity.

1991 ◽  
Vol 40 (2) ◽  
pp. 174-175
Author(s):  
G. Zanetta ◽  
G. Keeney ◽  
S. Cha ◽  
J. Katzmann ◽  
H.S. Wieand ◽  
...  

1998 ◽  
Vol 108 (2) ◽  
pp. 269-272 ◽  
Author(s):  
Adolfo Del Valle-Zapico ◽  
Fidel Fernández Fernández ◽  
Antonio Rubio Suárez ◽  
Carmelo Morales Angulo ◽  
Julio Rama Quintela

1992 ◽  
Vol 10 (12) ◽  
pp. 1839-1847 ◽  
Author(s):  
B G Haffty ◽  
M Toth ◽  
S Flynn ◽  
D Fischer ◽  
D Carter

PURPOSE This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer. METHODS AND MATERIALS Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale-New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow-cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis. RESULTS At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P < .02). Patients with low SPF (< 12%) experienced an 83% 5-year survival rate, compared with a 24% 5-year survival rate in patients with high SPF (> or = 12%) (P < .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P < .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence. CONCLUSIONS DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed.


2000 ◽  
Vol 20 (4) ◽  
pp. 197-203 ◽  
Author(s):  
Joerg Hemmer ◽  
Carmen Hauser

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. Fluorescencein situhybridization (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.


2001 ◽  
Vol 125 (3) ◽  
pp. 364-374
Author(s):  
Anil R. Prasad ◽  
George Divine ◽  
Richard J. Zarbo

Abstract Context.—DNA flow cytometry of breast cancer is a proposed tumor marker of prognostic significance that is of controversial clinical utility because of lack of standardization and confirmatory studies. Objective.—To evaluate the prognostic significance of the more informative technique of multiparametric 2-color DNA flow cytometry as recommended by the 1992 DNA Cytometry Consensus Conference. Design.—Three hundred thirty-two breast carcinomas with 7 to 12 years of follow-up were prospectively analyzed as fresh tumors that were mechanically dissociated into whole cell suspensions. These suspensions were dual fluorescence–labeled with propidium iodide (DNA) and antibodies to cytokeratin (epithelium) and leukocyte common antigen (internal leukocyte control) for gated analysis of subpopulations. Multicycle software with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell-cycle quantitation. Data were analyzed according to the DNA Flow Cytometry Consensus Conference recommendations. Results.—DNA ploidy and proliferation stratified into 3 categories were not predictive of overall or disease-free survival. Sixty-five percent of tumors were nondiploid, and 35.4% were diploid. Two hundred six tumors were able to be evaluated for synthesis-phase fraction (SPF) analysis, with 74 of 206 cases in the low range (&lt;13.4%), 36.4% in the intermediate range (&gt;13.5 to &lt;25.4%), and 27.6% in the high SPF (&gt;25.5%) category. Aneuploid tumors tended to have a higher SPF. Univariate survival analysis showed prognostic significance of the following: tumor size, stage, TNM components, vascular invasion, nuclear grade, and histologic grade. Only T classification, presence of positive axillary lymph nodes, and distant metastases were significant independent predictors of survival in multivariate Cox regression models. Age and hormone receptor status showed no prognostic significance. Synthesis-phase fraction was significantly correlated with tumor size, stage, T classification, nuclear and histologic grade, presence of estrogen or progesterone receptors, and axillary lymph node status. None of the histologic parameters showed any significant association with DNA aneuploidy, except for high nuclear and histologic grade and the absence of estrogen receptors. Conclusions.—Despite the use of state-of-the-art processing and flow cytometry analytic techniques, DNA ploidy and proliferation measurements were not predictive of survival in any stage of breast cancer. However, select histopathologic parameters and TNM stage were significant predictors of survival in univariate and multivariate analyses. We conclude that DNA ploidy and proliferation measurements do not provide significant prognostic information for clinicians to integrate into therapeutic decision making for patients with breast cancer.


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