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In patients with serous adenocarcinoma (SAC) of the endometrium, we evaluated the prognostic importance of clinicopathological parameters, DNA ploidy, and immunoexpression of p53, estrogen receptor (ER), progesterone receptor (PR), and Ki-67. In a series of 73 stage I and II SAC, DNA ploidy analysis was performed on hysterectomy specimens using DNA image cytometry. Immunohistochemical analysis of p53, ER, PR, and Ki-67 expression was additionally performed. In the review of the histological slides by three gynecologic pathologists, the presence of a serous component was not agreed upon in 17 (23 %) cases. The remaining 56 cases, consisting of pure SAC or SAC mixed with endometrioid adenocarcinoma, were further analyzed. Tumor recurrence was observed in 14 patients, and 28 patients died during the follow-up period. Patients with diploid (n = 19), aneuploid (n = 29), and tetraploid (n = 8) tumor had 5-year recurrence rates of 10, 38, and 53 %, respectively (p = 0.09). A DNA ploidy parameter, 5c exceeding rate, was found to be a prognostic marker for recurrence (p = 0.03), progression-free survival (p < 0.01), and overall survival (p = 0.02). Immunoexpression of p53, ER, PR, and Ki-67 did not have prognostic value, and the same was true for FIGO stage, lymphovascular invasion, the extent of myometrial invasion, and lymphadenectomy. The histological diagnosis of SAC may be difficult in some cases. Established clinicopathological parameters do not seem to be strong prognosticators in stage I and II disease. A DNA ploidy parameter, 5c exceeding rate, may be a prognostic marker in this patient group and should be further validated in larger series.

Background: We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index., Patients and Methods: High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium., Results: Patients with diploid (N = 728), aneuploid tumor with DNA index ≤ 1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤ 1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤ 1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis., Conclusions: The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.

DNA ploidy has been reported to be a prognostic marker for patients with endometrial carcinoma. In this study, DNA ploidy and histologic heterogeneity were evaluated by comparing curettage and hysterectomy specimens in 99 consecutive patients diagnosed with endometrial carcinoma. High-resolution DNA ploidy image analysis and review of histologic specimens were performed. The histologic subtypes were identical in 77 (78%) and differed in 22 (22%) cases. The DNA ploidy results were concordant in the curettage and hysterectomy specimens in 72 (72.7%) and discordant in 27 (27.3%) cases. Histologic heterogeneity was significantly associated with DNA ploidy heterogeneity (P=0.03). On the basis of histologic heterogeneity, DNA ploidy-discordant cases were divided into 2 groups. One group (16.2% of cases) consisted of specimens with similar histology in curettage and hysterectomy, all belonging to the endometrioid subtype. This group showed DNA ploidy discordance because of a DNA diploid peak in 1 specimen and an aneuploid peak (DI=1.05-1.2) in the other. The other group (11.1% of cases) consisted of cases with different histologic subtype or grade and showed a more pronounced DNA ploidy difference (diploid vs. aneuploid with DI>1.2). Our results suggest that the DNA ploidy results of the hysterectomy and curettage specimens are not identical. The difference observed, which we believe reflects the intratumoral heterogeneity, should be taken into account when applying DNA ploidy to endometrial carcinoma specimens.

Ovarian cancer is the most lethal of the gynecological malignancies. One of the aims of the ongoing research in this field is the search for prognostic and/or predictive factors which can contribute to a more individualized patient treatment. All studies performed at The Norwegian Radium Hospital with regard to the prognostic significance of DNA ploidy in borderline, early and advanced ovarian cancer, were reviewed. The conclusions emanating from these studies were compared to the international literature. DNA ploidy analysis is of definite independent prognostic significance in borderline and early (FIGO stage I) ovarian cancer, and is of help in the selection of patients expected to benefit from adjuvant chemotherapy, or in whom a more conservative surgical procedure can be acceptable. DNA ploidy status is also of prognostic significance in advanced ovarian cancer; however, for the time being this information has no direct consequences for patient treatment. We conclude that DNA ploidy analysis should be incorporated in the routine histopathological evaluation of borderline and early (stage I) ovarian cancer.

To evaluate the prognostic significance of DNA ploidy in endometrial stromal sarcoma, the traditional clinical and histopathological prognostic variables and DNA ploidy in 48 patients with histologically verified endometrial stromal sarcoma were analyzed. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the tumor were obtained in 47 patients. In univariate analysis, malignancy grade (P < 0.001), cellular atypia (P < 0.001), tumor diameter (P = 0.001), and mitotic count (P = 0.002) were highly significant. Also menopausal status (P = 0.011), FIGO stage (P = 0.035), and free resection margins at primary surgery (P = 0.026) obtained significance, while vessel invasion and age did not. DNA ploidy was not significant. In Cox multivariate analysis, free resection margins at primary surgery were found to be the most important prognostic factor (P < 0.001), followed by malignancy grade (P = 0.002), tumor diameter (P = 0.019), and menopausal status (P = 0.019). DNA ploidy did not obtain significance. Free resection margins at primary surgery, malignancy grade, tumor diameter, and menopausal status are important prognostic factors in endometrial stromal sarcoma.

In a prospective study of 465 patients with invasive carcinoma of the uterine cervix, the prognostic impact of flow cytometric parameters (ploidy level and fraction of S-phase cells) and clinical variables was evaluated. Median follow-up time was 57 (32-80) months. A total of 230 patients died of cervical cancer during follow-up. Ploidy level had no prognostic significance, neither when analyzed as diploid against nondiploid nor when utilizing different cutoff levels for DNA index (1.3, 1.5, and 1.7). The fraction of S-phase cells (SPF) could be evaluated in 91% of the diploid cases but in only 22% of nondiploid cases. SPF had no prognostic impact. In multivariate analysis, FIGO stage was the only independent prognostic factor (P < 0.001). There was no difference between squamous cell, adeno, and adenosquamous carcinomas. A radical hysterectomy with pelvic lymphadenectomy was performed in 123 cases in stage I-IIA. In this subgroup, tumor size (P = 0.001), infiltration into the parametria (P = 0.005), vessel invasion (P = 0.008), and metastasis to the common iliac nodes (P = 0.013) obtained independent statistical significance in multivariate analysis, while ploidy level had no significance. Neither DNA ploidy nor S-phase analyses should be used in treatment planning.

To analyze the significance of DNA ploidy in uterine leiomyosarcoma, the traditional clinical and histopathological prognostic variables and DNA ploidy were studied in 70 patients with histologically verified uterine leiomyosarcoma. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the tumor were obtained in 58 patients. In univariate analysis tumor diameter, FIGO stage and presence of residual disease after primary surgery were highly significant (p < 0.001) and also DNA ploidy (p = 0.043), age (p = 0.017), and menopause status (p = 0.028) obtained significance. Cellular atypia was almost significant (p = 0.056), while mitotic count, malignancy grade and vessel invasion were not. In Cox's multivariate analysis, FIGO-stage was found to be the most important prognostic factor (p < 0.001), followed by cellular atypia (p = 0.007) and tumor diameter (p = 0.016). DNA ploidy did not obtain significance when categorized as diploid/non-diploid. Patients with tumors with multiple aneuploid cell populations had a very poor prognosis. When categorized as multiple aneuploidy versus all other ploidy groups, DNA ploidy obtained marginal significance in multivariate analysis (p = 0.054). Tumor diameter, stage and cellular atypia are important prognostic parameters in uterine leiomyosarcomas.

Background: The prognostic significance of flow cytometric DNA ploidy and S-phase fraction (SPF) in ovarian cancer has been controversial. In the current study, the authors analyzed tumor heterogeneity in respect to DNA index DI and SPF., Methods: Flow cytometric variation in DI and SPF among representative fresh tumor material from the primary tumor, metastasis, and malignant effusions from the same patient was analyzed., Results: One hundred thirty-two samples from 47 patients were analyzed, and 119 samples from 42 patients were evaluable. Stable DI between different samples was found in 34 patients, whereas heterogeneity was found in 8 patients (19%). The metastases showed stable DNA content. The malignant effusion samples often lacked tumor cells. The representative ones were often DNA diploid. In 21% of the aneuploid samples, the SPF could not be analyzed. In 38% of the aneuploid samples, the stem line constituted less than 15% of measured nuclei. In these samples, a negative correlation between SPF and percentage of aneuploid cells was found, making SPF unreliable. Correct SPF measurement was thus possible in only 41% of the aneuploid samples, and in these tumors, SPF values varied considerably among different samples from the same patient, illustrated by a median SPF difference of 11% (range, 0-28%)., Conclusions: Tumor DI heterogeneity existed in 19% of tumors. SPF depended on the amount of aneuploid cells in case of small stem lines and varied considerably, making its use as a prognostic factor doubtful. To ensure that all tumor stem lines are represented, at least two biopsy specimens from any solid tumor should be analyzed.

Objective: Our goal was to study the prognostic value of deoxyribonucleic acid ploidy and S-phase fraction in advanced ovarian carcinoma., Study Design: Prognostic factors for corrected survival were evaluated in a prospective study including 169 patients with stage III and IV ovarian cancer treated between 1985 and 1990., Results: A total of 79% of the tumors were deoxyribonucleic acid aneuploid. Deoxyribonucleic acid aneuploidy was associated with grade of differentiation. S-phase fraction could be calculated in all deoxyribonucleic acid euploid tumors and 76% of the deoxyribonucleic acid aneuploid tumors. By multivariate analysis deoxyribonucleic acid ploidy, histologic type and grade, age, International Federation of Gynecology and Obstetrics stage, and amount of residual tumor were independent prognostic variables for corrected survival. On the basis of Cox regression a relative risk for the individual patient could be calculated., Conclusion: Deoxyribonucleic acid ploidy gives additive prognostic information and is a useful parameter for dividing patients with advanced ovarian cancer into risk groups for treatment decisions.

Objectives: Our purpose was to identify prognostic factors in stage I epithelial invasive ovarian carcinoma., Study Design: The traditional clinical and pathologic prognostic variables and deoxyribonucleic acid ploidy were analyzed in a group of 290 patients., Results: A multivariate analysis identified degree of differentiation as the most powerful prognostic indicator of disease-free survival, followed by deoxyribonucleic acid ploidy and, finally, International Federation of Gynecology and Obstetrics (1986) stage. Tumors with clear cell carcinoma elements were not graded, and in this subgroup International Federation of Gynecology and Obstetrics (1986) stage was the most important prognostic characteristic. When the effects of the three most important factors were accounted for in graded tumors, then none of the following were prognostic: histologic type, dense adhesion, extracapsular growth, ascites, rupture during surgery, International Federation of Gynecology and Obstetrics (1973) stage, size of tumor, and age and type of adjuvant treatment. None of 77 patients with well differentiated deoxyribonucleic acid diploid tumors had relapses., Conclusion: Deoxyribonucleic acid ploidy is an important new independent prognostic factor in stage I ovarian carcinoma.

The DNA content in 37 tumors from 34 women with gynecological cancer was measured by flow cytometry (FCM) and interactive image cytometry (ICM). Agreement was obtained in 81% of cases as regards ploidy levels, but seven tumors (19%) showed different ploidies. Of these, five were classified as diploid by FCM but either aneuploid (three cases) or polyploid (two cases) by ICM. Two other tumors were aneuploid by ICM but polyploid (one case) and unclassifiable (one case) by FCM. All tumors classified as aneuploid by FCM were also aneuploid by ICM, and all tumors classified diploid by ICM were also diploid by FCM. Of six patients whose tumors were classified as euploid (five diploid and one polyploid) by FCM but classified as aneuploid by ICM, five relapsed, and three of these have died of disease. On the basis of these findings, it is concluded that ICM must be performed in cases classified as diploid by FCM to ensure that small subpopulations of aneuploid tumor cells are not overlooked.