Prognostic value of nuclear DNA quantification and cyclin A expression in epithelial ovarian carcinoma

OBJECTIVE: To investigate the correlation of DNA ploidy, S-phase fraction (SPF) and the expression of cyclin A to the clinical prognostic factors in patients with epithelial ovarian cancer. STUDY DESIGN: A prospective analysis was performed on 46 ovarian tumor patients. The DNA ploidy and SPF were determined by flow cytometry and the expression of cyclin A was measured by immunohistochemical staining. RESULTS: Compared with benign and borderline tumors, the malignant tumors expressed higher levels of cyclin A (P=0.007), more aneuploid cells (P=0.018) and higher SPF (P=0.015). With regard to DNA ploidy and the clinical prognostic factors, aneuploid cells increased with tumor grade (P=0.011), the disease stage (P=0.009) and residual volume (P=0.001). When residual tumor was more than 2 cm, the expression of cyclin A was increased (P=0.043). Three-year survival was low for patients with tumors expressing cyclin A in over 10% of cells (P=0.003). CONCLUSIONS: The data suggest that the assessment of the DNA ploidy, SPF and the expression of cyclin A may provide important information for predicting the prognosis of epithelial ovarian cancer.     

DNA ploidy level and cell cycle distribution in ovarian cancer: relation to histopathological features of the tumor

We analyzed nuclear DNA content and S-phase fraction (SPF) from 157 paraffin-embedded ovarian tumors by flow cytometry and compared the results with the clinicopathological features of the tumors. DNA aneuploidy was more common and mean SPF was higher in advanced than in early-stage tumors (p less than 0.001). DNA aneuploidy was most often (75%) observed in undifferentiated tumors (World Health Organization classification) and most seldom (30%) in mucinous carcinomas. Mean SPF values ranged from 17.7% in undifferentiated carcinomas to 11.1% in mucinous carcinomas. DNA flow cytometric results correlated better with nuclear than with histological tumor grade. The proportion of DNA-aneuploid tumors increased from 30% in nuclear grade I to 93% in nuclear grade III, and mean SPF increased from 9.9 to 20.2% (p less than 0.001). DNA ploidy and SPF were independently associated with both stage and nuclear grade of the tumor, whereas the differences between the histopathological tumor types virtually disappeared when the groups were adjusted for nuclear grade. On the basis of these clinicopathological correlations, it appears that DNA ploidy and SPF reflect the malignant potential of ovarian tumors and thus complement the routine histopathological evaluation.     

Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer

The immunohistochemical expression of HER-2/neu and cytofluorimetric data were retrospectively analyzed in a group of primary advanced ovarian cancers. Thirty-three out of 94 (35%) cases showed a specific p185/neu immunoreaction. No correlation between p185/neu expression and any of the clinico-pathologic parameters examined was observed. As far as cytofluorimetric data are concerned, 38 out of 69 (55%) of the tumors were diploid (DNA index = 1) while 31 (45%) were aneuploid (DNA index from 1.10 to 2.50 with a median value of 1.50). Ovarian tumors were defined as of low and high S-phase fraction in 68% and 32% of the cases, respectively. Tumor ploidy and S-phase fraction did not correlate with the clinico-pathologic characteristics or p185/neu oncoprotein expression. Aneuploid tumors had a higher S-phase fraction (mean: 15.81 ± 13.44) than diploid tumors (mean: 8.89 ± 7.98) ( P < 0.01). p185/neu expression failed to affect significantly both overall and progression free survival. On the other hand tumor ploidy was found to be related to the prognosis of advanced ovarian cancer patients although the difference was not statistically significant. As far as progression free survival is concerned, the median time to recurrence was not reached for diploid cases whereas it was 21 months for aneuploid cases ( P < 0.05). The 5-year survival for patients with a low S-phase fraction (58%) was significantly higher than for patients with high S-phase fraction tumors (28%) ( P < 0.01). Median time to recurrence was 48 and 17 months for low and high S-phase fraction tumor patients, respectively ( P < 0.05). However, in a multivariate analysis both tumor ploidy and S-phase fraction did not retain their prognostic value. The assessment of the role of the parameters examined in improving the prognostic characterization of ovarian cancer patients should be investigated in large multicenter clinical trials.     

Flow cytometric analysis of cellular DNA content in ovarian cancer

A total of 169 paraffin-embedded tissue sections from 42 patients with epithelial ovarian cancer were subjected to analysis of cellular DNA content by flow cytometry. Twenty-three cases were found to be homogenously diploid, whereas 19 cases were aneuploid. A "mosaic" type containing both aneuploid and diploid cell populations was found in 11 of 19 aneuploid cases. Clinical features showed significant correlation with tumor ploidy of FIGO stage and bulky disease. In evaluation of the prognostic value of tumor ploidy, "mosaic" tumors were frequently observed in women who died of disease (DOD), whereas women with diploid tumors survived longer than those with "mosaic" tumors. The present results suggest that determination of DNA heterogeneity may be a valuable parameter in the prognosis of epithelial ovarian cancer.     

Nuclear deoxyribonucleic acid heterogeneity of ovarian borderline malignant serous tumors

Sixteen borderline malignant serous ovarian tumors and seven well-differentiated invasive serous ovarian carcinomas were examined with the technique of Feulgen microspectrophotometry for the determination of nuclear deoxyribonucleic acid (DNA) ploidy patterns (diploid versus aneuploid) and ploidy levels of the stem cell lines. Of the nine stage I-II borderline malignant tumors, only one (11%) was aneuploid. In contrast, four of seven (57%) stage III borderline malignant neoplasms and all stage III carcinomas were aneuploid. The stem cell modal values in all borderline serous tumors were less than triploid (3N) while in five of seven carcinomas stem cell modal values were greater than triploidy. This contrast in ploidy patterns and ploidy levels may explain the differences in biologic behavior between borderline malignant serous tumors and invasive serous carcinomas of the ovary.     

上皮性卵巢癌DNA含量、细胞核形态及其对患者预后价值的探讨

目的：探讨ＤＮＡ含量、核形态参数对预测上皮性卵巢癌患者预后的价值。方法：应用计算机图像分析系统测定原发性上皮性卵巢癌３２例的细胞核ＤＮＡ含量、倍体水平、面积、周长及形状因子５个参数。结果：卵巢癌临床晚期及转移病例的ＤＮＡ含量明显增高，与早期及无转移组相比，差异均有显著性（Ｐ＜０．０２５）。６３％为异倍体肿瘤，３７％为二倍体肿瘤。组织学Ⅰ、Ⅱ、Ⅲ级的异倍体率分别为３８％、５７％、９０％，呈递增趋势。Ⅰ级与Ⅲ级相比，差异有显著性（Ｐ＜０．０５）。腹水阳性组及转移组的异倍体率明显增加，分别为７３％及７６％。ＰＣＮＡ阳性组及阴性组的核形状因子差异有显著性（Ｐ＜０．０５）。核面积和周长在诸预后因素间差异无显著性（Ｐ＞０．０５）。结论：细胞核ＤＮＡ含量和倍体水平是影响卵巢癌患者预后的重要因素；核形状因子亦可作为评估肿瘤生物学行为的一项指标。     

Prognostic significance of preoperative DNA flow cytometry in surgically-treated cervical cancer

OBJECTIVE: To evaluate the prognostic significance of preoperative DNA flow cytometry compared with other clinical and histologic variables in cervical carcinoma. STUDY DESIGN: Sixty-four patients with FIGO Stage Ib-II cervical cancer treated with radical abdominal hysterectomy and systematic pelvic lymphadenectomy were analyzed. The mean follow-up was 3.4 (range 0.3-9.8) years. DNA flow cytometry was performed with fresh tumor tissue. Four biopsies were recut from the surgical specimen within 30 minutes of the operation. The ectocervix was divided into four quadrants and a specimen obtained from each. DNA-low-grade tumors (diploid, near-diploid, tetraploid and near-tetraploid) were distinguished from DNA-high-grade tumors (aneuploid and hypoploid). Carcinomas with more than one non-diploid stem line were considered heterogeneous. An S phase fraction >7% was classified as low, 7% - < 14% as moderate, and > or = 14 as high. DNA ploidy, DNA heterogeneity, S phase fraction and various clinical and histological variables were related to disease-free survival. RESULTS: In the univariate analysis patients with DNA-low-grade carcinomas had significantly better disease-free survival than patients with DNA-high-grade tumors (82% vs 45%, p = 0.021). Carcinomas with an S-phase fraction < 7% were associated with better disease-free survival (0.8) than those with an S-phase fraction 7% - > 14% (0.62) and those with > or = 14% (0.64), but this was not statistically significant. Cox stepwise regression analysis showed DNA-heterogeneity, age, grade, parametrial involvement and extrapelvic metastasis to be independent prognostic factors. CONCLUSION: DNA ploidy and DNA heterogeneity are of prognostic importance in cervical cancer. DNA flow cytometry may be used preoperatively to identify low-risk and high-risk patients within a given stage.     

Effect of cellular DNA content on the prognosis of epithelial ovarian cancers

OBJECTIVE: To assess the cellular DNA status of epithelial ovarian cancers with regard to clinicopathological findings and its effect on prognosis. MATERIALS AND METHODS: Twenty-six consecutive patients with a diagnosis of epithelial ovarian cancer who had been treated by primary surgery and six courses of platinum-based chemotherapy were enrolled in this study. Second-look laparotomy (SLL) was performed in all cases following confirmation of the clinical remission state. Surgical stage, tumor grade, initial tumor volume, residual tumor volume, histopathologic differentiation, and SLL findings were analyzed in correlation with DNA ploidy and DNA index. DNA analysis was performed via DNA flow cytometry through paraffin-embedded tissue specimens. RESULTS: Of 26 patients, flow cytometric studies revealed 16 aneuploidy cases (61.5%). DNA index values ranged from 1.1 to 1.82 (average 1.29 +/- 0.28). The flow cytometry coefficient of variation mean value was set to 6.7. Taking the cutoff value of 1.2 for DNA indices, a fairly good correlation was detected between DNA ploidy and DNA indices (p < 0.001). The aneuploidy incidence was found to be high in advanced and poorly differentiated tumors (p < 0.05). There was statistically more residual tumor volume in aneuploid tumors during primary cytoreductive surgery and also higher recurrence rates following six courses of chemotherapy compared with diploid tumors (p < 0.05). No significant correlation was detected between the histopathologic subtypes and tumor volume (p > 0.05). Residual tumor volumes were larger in cases with DNA indices of 1.2 yielding higher residual tumor volume following surgery and being in good correlation with SLL results (p < 0.05). The mean survival rates of cases with aneuploid tumor and a DNA index of >1.2 were low compared to those with diploid tumors and DNA indices of <1.2 tumors (p < 0.05). CONCLUSION: DNA ploidy and DNA indices are important prognosticators for malignant epithelial ovarian tumors. They should be evaluated together with the patient's clinical status and other prognostic factors.     

Cell proliferation in ovarian carcinoma: superior accuracy of S-phase fraction (SPF) by DNA labeling index versus flow cytometric SPF, lack of independent prognostic power for SPF and DNA ploidy, and limited effect of SPF on tumor growth rate

OBJECTIVES: The goal of this work was to test the hypotheses that S-phase fraction (SPF) by DNA labeling index (SPF-LI) would predict the course of the disease for ovarian/peritoneal carcinomas and that SPF-LI would correlate better with pathologic classification and outcome than SPF by DNA flow cytometry (SPF-F). METHODS: Tritiated thymidine (1985-1988) and bromodeoxyuridine (1988-1999) DNA labeling (SPF-LI) was evaluated in vitro on 178 tumors. Cellular DNA and SPF-F were measured flow cytometrically. During this time, 90% of ovarian/peritoneal tumors accessioned in surgical pathology were studied. RESULTS: Tumors of low malignant potential (LMP, "borderline") had low SPF-LI (median = 1.2%). High-grade invasive carcinomas of various types and carcinosarcomas all had high SPF-LI (medians = 11.2-23.4%). Serous low-grade invasive carcinomas (median = 1.05) resembled LMP tumors. SPF-LI of ovarian carcinomas other than LMP tumors increased slightly as FIGO stage increased (P = 0.07). Survival of patients with high-grade ovarian carcinomas was not predicted by SPF-LI or SPF-F, nor was DNA ploidy predictive. SPF-LI produced tighter distributions for various tumor types than did SPF-F. Neither SPF nor DNA ploidy contributed to prediction of outcome when tumor type and stage were included in multivariate models. We calculated the mean cell loss rate of high-grade carcinomas to be 94%. CONCLUSIONS: LMP ovarian/peritoneal tumors have low proliferation rates in contrast to high-grade carcinomas. Proliferation correlated with tumor type and stage, but neither it nor DNA ploidy predicted survival independently. Proliferation rate is growth limiting only when low. At higher levels cell loss limits growth. SPF-LI measures proliferation more accurately than SPF-F; SPF-F is not sufficiently reliable for clinical use.     

Flow cytometric DNA ploidy analysis of ovarian granulosa cell tumors

The nuclear DNA content of 50 ovarian tumors initially diagnosed as granulosa cell tumors was measured by flow cytometry using paraffin-embedded archival material. The follow-up period of the patients ranged from 4 months to 19 years. Thirty-eight tumors were diploid or near-diploid, while 5 were aneuploid. DNA profiles of 7 tumors could not be evaluated. All 50 tumors were immunohistochemically tested for expression of intermediate filament proteins vimentin and cytokeratin and epithelial membrane antigen. The cells of all but 3 tumors expressed vimentin. These 3 vimentin-negative tumors were positive for cytokeratin and epithelial membrane antigen. They were highly aneuploid and though originally diagnosed as granulosa cell tumors, most likely represent undifferentiated carcinomas. Hence, only 2 typical granulosa cell tumors were aneuploid. In addition, frozen tissue samples from 9 of 10 granulosa cell tumors showed a DNA diploid content. Our results indicate that granulosa cell tumors tend to be diploid or have only minor ploidy abnormalities which is in line with their relatively benign character. An undifferentiated carcinoma should be considered in the differential diagnosis of tumors with a high DNA index.     

Prognostic significance of tumor ploidy in patients with advanced ovarian carcinoma

Fresh tumor specimens obtained from 53 consecutive patients with FIGO Stage III ovarian carcinoma were analyzed by flow cytometry. All patients were treated by a standard protocol: maximal tumor excision and cisplatin/cyclophosphamide/adriamycin chemotherapy, and followed-up for at least 24 months. Thirty-two percent of tumors were diploid (DNA index = 1.00) and 68% aneuploid (DNA index greater than 1.00), with more aneuploid tumors being associated with larger residual tumor and poor cellular differentiation. Patients with diploid tumors were found to survive significantly better than those with aneuploid tumors, in terms of survival rate (65% versus 31%), median survival time (33 months versus 13 months), and mean disease-free interval (17.8 months versus 8.2 months). The influence of the amount of residual tumor after primary surgery on survival was only significant in patients with diploid tumors. Our results support previous findings that tumor ploidy is an important prognostic indicator in ovarian cancer. We found aneuploidy to be associated with a poorer clinical outcome in Stage III disease, regardless of the amount of residual tumor after primary surgery and the degree of cellular differentiation.     

Flow-cytometric prognostic factors for the survival of patients with ovarian carcinoma: a 5-year follow-up study

Fresh surgical specimens of 37 patients with previously untreated ovarian carcinomas were investigated by means of flow cytometry. The aim of the study was to look for cellular prognostic factors, in addition to the well-known clinical prognostic factors, of survival time for these patients. All patients underwent chemotherapy after surgery, and all patients had a minimum of 5 years of follow-up. Patients with diploid or near-diploid tumors (DNA index less than or equal to 1.25) survived significantly longer than those with aneuploid tumors (DNA index greater than 1.25, P = 0.02). Patients whose tumors showed a high proportion of SG2M phase cells (greater than 17%) or a low proportion of G0/G1 phase cells had shorter survival times than those with tumors with a low proportion of SG2M phase tumor cells (less than or equal to 17%, P = 0.01) or a high proportion of G0/G1 phase tumor cells. There is no significant relationship between cytometric data and stage. Different surgical procedures, cytostatic treatment, histological tumor type, and differentiation had no significant effects on the survival time of patients in this study. Thus, the data from this study demonstrate strong cytometric prognostic factors of the survival of patients with ovarian carcinomas.     

Tissue expression of CA-125 and carcinoembryonic antigen in ovarian carcinoma in relation to nuclear DNA content, histologic grade, and patient survival

In a prospective study the immunohistochemically detectable tissue expression of the antigens CA-125 and CEA in 112 epithelial ovarian carcinomas and 23 borderline tumors was related to histologic features of the tumor and to patient survival. The CA-125 antigen was expressed mainly in non-mucinous tumors, with no evident association between histologic grade and immunoreactivity. CEA was expressed in mucinous tumors regardless of tumor grade. Flow cytometric DNA analysis was performed on fresh frozen tissue in a subgroup of 60 cases. There was no association between DNA ploidy or S-phase fraction and the CA-125 or CEA antigen expression. Tumor stage, size of residual tumor masses after surgery and DNA ploidy had independent associations with patient survival in multivariate log-rank analysis of prognostic factors. However, there was no association between the CA-125 or CEA antigen expression and patient survival. Thus, in ovarian carcinoma the expression of the CA-125 and CEA antigens seems to be independent of the inherent malignant potential of the tumor epithelium, while DNA analysis provides valuable prognostic information.     

The relationship of steroid receptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors

Tumor specimens from 92 patients with ovarian carcinoma were analyzed for estrogen receptor (ER), progesterone receptor (PR), proliferative fraction, and ploidy. Seventy-one percent of tumors were either ER+ (greater than 5 fmole/mg protein) or PR+ (greater than 10 fmole/mg protein) with 27% of tumors overall being both ER+ and PR+. There was no significant relationship between receptor expression and stage, grade, or histological subtype. Thirteen percent of diploid tumors were receptor negative in contrast to 38% of aneuploid tumors (P less than 0.01). There was no significant association between ER status and ploidy, but 60% of diploid tumors were PR+ in contrast to 33% of aneuploid tumors (P less than 0.02). Eleven percent of tumors overall were both ER rich and PR rich and comprised 23% of diploid and 5% of aneuploid tumors (P less than 0.01). Receptor-negative tumors had a median S phase of 18.8% which was significantly higher than the median S phase of 12% in receptor-positive tumors (P less than 0.02). A similar analysis was also performed on specimens from 9 patients with borderline epithelial ovarian tumors and 12 with benign epithelial ovarian tumors. Up to 50% of benign and borderline epithelial tumors had measurable receptors, but all were diploid with a relatively low S phase fraction. The functional significance of steroid receptor expression in ovarian cancer is unclear, but the association with ploidy and proliferative activity particularly in patients with malignant ovarian tumors may allow better identification of prognostic subsets and aid in selection of patients for hormonal therapy.     

DNA ploidy, morphometry, and nuclear grade as prognostic factors in endometrial carcinoma

In a retrospective analysis of 106 cases of endometrial carcinoma stages I-IV (FIGO), the prognostic value of DNA ploidy and nuclear morphometry of tumor cells was evaluated and compared with that of conventional clinical and histopathologic parameters. Paraffin-embedded tumor tissue from the original curettage specimens was used. A flow cytometric technique was employed to distinguish diploid from aneuploid tumors. It was not possible to estimate S-phase rates by this method. Eight different nucleus-related morphometric parameters were computed from representative tumor regions on the original slides. All histologic specimens were reviewed by on the pathologist and graded according to FIGO; nuclear grade was determined separately. Tumor stage, depth of myometrial infiltration, and nuclear grade were the most important prognostic factors with regard to tumor-related survival. DNA ploidy and nuclear morphometry did not add significant prognostic information that could be used to distinguish high-risk and low-risk populations with endometrial carcinomas. The simple nuclear grading system should be further evaluated in prospective studies and compared with DNA analysis and nuclear morphometry performed on fresh-frozen tissue.     

DNA flow cytometry of ovarian tumors with correlation to histopathology

Tissue samples from 49 women with seven benign and 42 malignant ovarian tumors were examined by means of DNA flow cytometry (FCM). The FCM data (DNA-ploidy and the number of S-phase fractions) were compared with the International Federation of Gynecology and Obstetrics (FIGO) stage, the histologic grade of differentiation and in some cases with the clinical outcome. The benign ovarian tumors were all diploid with a mean of 2.1% (+/- 1.66) S-phase fractions. Adenocarcinomas with the histologic grade 1 were diploid and had a mean of 2.1% (+/- 1.17) S-phase fractions. Grade 2 adenocarcinomas were aneuploid in eight of nine cases and revealed an increased proliferative activity (7.7% +/- 2.67 S-phase fractions). A high number of aneuploid cases (nine of 13) and an increased DNA synthesis were found in grade 3 adenocarcinomas (12.0% +/- 5.72 S-phase fractions). Four of six malignant nonepithelial tumors also had high numbers of S-phase fractions (9.7-14.5%). A significant correlation between the histologic grade and the DNA synthesis, FIGO stage, and DNA-ploidy was found. DNA-FCM may be used as an additional diagnostic tool supplementing routine histopathologic examination of ovarian tumors for better biological characterization, especially for those with uncertain grading, for grade 2 neoplasms, and for malignant nonepithelial tumors.     

Flow cytometric measurements of DNA index and S-phase on paraffin-embedded early stage endometrial cancer: an important prognostic indicator

Paraffin-embedded curettage material from 120 patients with stage I and II endometrial cancer were analyzed by flow cytometry. The follow-up time in all cases was at least 5 years or until death. It was possible to determine DNA ploidy in 111 cases and S-phase was also evaluated in 92/111 cases. DNA ploidy and S-phase were then compared with the FIGO grading and clinical outcome. DNA ploidy results showed that 11% of grade 1 tumors were aneuploid, 14% of grade 2, 42% of grade 3, and 85% of the cases of uterine papillary serous carcinoma (UPSC) were aneuploid. Patients with tumors that showed an S-phase fraction below 5% had a cumulative 5-year cancer mortality of 7% whereas 49% of the patients with tumors having S-phase fraction above 10% died of their cancer. The prognostic significance of DNA and S-phase correlated fairly well with the FIGO grading as determined by a pathologist with special interest in gynecologic oncology and the DNA parameters added prognostic information independent of the FIGO grading.     

DNA content in juvenile granulosa cell tumors of the ovary: a study of early- and advanced-stage disease.

Paraffin-embedded tissue from 38 patients with early- and advanced-stage juvenile granulosa cell tumor (JGCT) of the ovary was analyzed by flow cytometry to investigate whether the DNA content is related to the histologic features, stage, or clinical outcome. Thirty-three cases were suitable for analysis: twenty-seven Stage Ia, two Stage Ic, and four Stage III. Eighteen (55%) tumors were DNA diploid and fifteen (45%) tumors were DNA aneuploid with a mean S-phase fraction (SPF) of 13.6% and a range of DNA indices from 1.0 to 2.2. Neither the DNA ploidy nor the SPF was associated with the stage of the disease. An analysis of the relation between DNA content and histopathologic features revealed that aneuploidy was associated with high mitotic rates and to a lesser extent with high-grade nuclear atypia. DNA aneuploidy was not associated with aggressive behavior of Stage Ia JGCTs. However, among the four patients with Stage III tumors, the two with diploid, low-SPF tumors were alive and well, whereas the two with aneuploid, high-SPF tumors developed recurrences or died. These data suggest that further studies on the prognostic significance of flow cytometric analysis of DNA content in advanced-stage JGCTs are warranted.     

Tumor DNA content as a prognostic feature in advanced epithelial ovarian carcinoma

Tumor DNA content (ploidy) was determined in 84 patients with epithelial ovarian carcinoma. Stage II-IV. A total of 251 DNA histograms generated by flow cytometry on cells derived from paraffin-embedded specimens were analyzed retrospectively. Of the 84 patients, 44 had tumors which were aneuploid, whereas 33 had diploid, and 7 had tetraploid tumors. Cox regression analysis revealed that age (P less than 0.001), stage (P less than 0.001), and ploidy (P less than 0.001) were independent prognostic features. The median survival time was 19 months and 48 months, respectively, in aneuploid and euploid tumors (P less than 0.001). The size of residual after surgery lost its significance when corrected for stage. Multivariate analysis in Stage III tumors revealed that ploidy was the most important prognostic factor (P less than 0.001) followed by age (P less than 0.025). A remarkable stability of cellular DNA content was found when the primary tumor was compared to the following groups: (1) various metastatic specimens from the primary operation in the same patient; (2) specimens analyzed sequentially from primary, secondary, and tertiary exploratory laparotomy; and (3) peritoneal washings before and after intraperitoneal chemotherapy.     

Cytogenetic and cytometric analyses in squamous cell carcinoma of the uterine cervix

Cytometric methods allow a division of tumors into a near-diploid and an aneuploid group. In most carcinomas, aneuploidy has been associated with poor prognosis, but as regards squamous cell carcinomas of the uterine cervix, the results are conflicting. The introduction of flow cytometry, a reliable and rapid method for determination of ploidy level and S-phase rate, has resulted in a renewed interest in cytometric studies of cervical carcinomas. In this article, DNA content, S-phase rate, and tumor heterogeneity are reviewed, as well as correlations found between DNA patterns and stage, age, menopause, differentiation, malignancy grading systems, ABH blood group antigens, and prognosis. In summary, aneuploidy is more common in stages III and IV and correlates to aggressive histopathology, but because of a higher degree of radioresponsiveness, the biological differences between aneuploid and near-diploid tumors are not consistently reflected in prognosis. High S-phase rates are correlated both to aggressive histopathology and impaired short-term prognosis.