Relationships between c-Ki-ras Mutations, HPV Types, and Prognostic Indicators in Invasive Endocervical Adenocarcinomas

Objective. Ras gene mutations have been identified in squamous cell carcinomas of the cervix and are associated with advanced-stage tumors. The current study was designed to determine the prevalence of c-Ki-ras mutations in invasive endocervical adenocarcinomas and associations between mutations, HPV status, and known prognostic indicators. Methods. Paraffin-embedded tissue samples from 32 cases of invasive adenocarcinoma of the endocervix were analyzed for the presence of c-Ki-ras mutations by amplification of DNA extracted from paraffin blocks using the polymerase chain reaction (PCR) and subsequent restriction enzyme digestion of the amplimers. This method allows detection of aspartic acid mutations of the c-Ki-ras gene at codons 12 and 13. Samples were also analyzed for the presence of HPV DNA using PCR and either "consensus sequence" primers or "type-specific" primers for HPVs 16 and 18. Patients' charts were reviewed for clinical information and correlations between clinical outcome and known prognostic indicators and the presence of c-Ki-ras mutations was assessed. Results. c-Ki-ras codon 12 mutations were detected in only 4 of the 32 cases (12.5%) of invasive endocervical adenocarcinomas examined. No codon 13 mutations were detected. Fifty-nine percent of the cases were HPV 16 or HPV 18 DNA positive and only 1 of the 4 cases with a codon 12 mutation was associated with HPV 16 or HPV 18. There were no significant associations between stage or grade of tumor or outcome and the presence of codon 12 mutations. However, using the observed survival as computed by the Berkson Gage Method at 12 months, the estimated median survival for patients with c-Ki-ras codon 12 mutations is 29 months compared to 68 months for patients lacking codon 12 mutations. Conclusions. These results indicate that c-Ki-ras codons 12 and 13 mutations are uncommon in invasive endocervical adenocarcinomas.     

Human papillomavirus and its prognostic significance in invasive carcinoma of the cervix in young patients.

Of 1,200 Chinese patients treated for carcinoma of the cervix between 1975 and 1984, those aged 40 years (n = 70) or less had a poorer prognosis. Of the latter group, 71% had disease classified as less than International Federation of Gynecology and Obstetrics (FIGO) stage Ib, and in 91% the disease was less than stage IIa; however, the 5-year survival of the 45 patients with verified invasive carcinoma was 75% compared with 82% for the overall group. The polymerase chain reaction (PCR) was used to test for the presence of human papilloma virus (HPV) types 16 and 18 within paraffin-embedded tissue from the primary tumors. HPV-16 DNA sequences were detected in 69% of the cases, HPV-18 DNA sequences in 44%, and in 31% both HPV-16 and -18 DNA could be identified. Of the cases of invasive carcinoma, 82% (37 of 45) contained DNA of HPV types 16 and/or 18. The effects of the presence or absence of HPV DNA on known prognostic factors was investigated. Although the influence of traditional factors, especially lymph node involvement, was confirmed, careful statistical analysis could not demonstrate a prognostic influence for HPV-16/18.     

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.     

Invasive cervical cancer in young women. Clinicopathologic correlation and demonstration of human papillomavirus by in situ hybridization.

It has been suggested that invasive cervical carcinoma is biologically more aggressive in young patients than in older patients. The clinicopathologic characteristics and human papillomavirus (HPV) status of women < or = 35 years of age with invasive cervical carcinoma treated at Emory University Hospital from 1985-1989, were evaluated in a retrospective study. The group consisted of 23 patients, 35% of all patients with invasive cervical carcinoma. Age at diagnosis, clinical stage, histologic classification, lymph node status, treatment and clinical follow-up were obtained from medical records. HPV status was evaluated by colorimetric in situ hybridization for HPV types 6, 11, 16, 18, 31, 33 and 35 in archival formalin-fixed paraffin-embedded tumor material available from 16 of the patients. This study found that the young patients had lower survival and greater extent of disease than predicted by clinical staging. The rate of detection of HPV (69% positive) and HPV typing (type 16 predominated) in these young patients showed no difference from other series of cervical carcinomas from all age groups. Although a higher proportion of patients who died of disease had HPV-negative tumors (3/7, 43%) than those patients who were alive and free of disease (2/9, 22%), this difference was not statistically significant (P = .73, Fisher's Exact T-Test).     

Advanced-stage serous borderline tumors of the ovary: a clinicopathological study of 49 cases.

There is controversy about patient outcomes and pathological parameters of prognostic significance in patients with stage II or stage III ovarian serous borderline tumors. Forty-nine cases of stage II and III ovarian serous borderline tumors were identified on review of the medical records at Vancouver Hospital and British Columbia Cancer Agency for the period from 1979 to 1996. Pathological features assessed included presence of micropapillary architecture, tumor cell DNA content (ploidy), and characteristics of the extraovarian implants, including invasiveness and mitotic activity. Clinical follow-up information (3-17 years of follow-up) was obtained for 48 patients. Fifteen patients had stage II tumors and 34 had stage III tumors. Fourteen patients experienced tumor recurrence 1 to 8 (mean 3.5) years after presentation and of these, six patients died of disease (2, 3, 4, 7, 10, and 11 years after presentation). Patients with gross residual disease, as assessed by the surgeon, more frequently experienced a recurrence compared with patients without gross residual disease, but this difference did not reach statistical significance (0.05相似文献   

Ploidy analysis of epithelial ovarian cancers using image cytometry.

We used a computerized image analysis system to determine the DNA content of 103 epithelial ovarian cancers using touch imprints of frozen tumor samples. Similar to prior studies of ploidy using flow cytometry, we found that most ovarian cancers (78%) were aneuploid while a minority (22%) were diploid. There was no relationship between ploidy and stage, histologic grade, or the ability to perform optimal cytoreductive surgery. Also, like prior studies using flow cytometry, negative second-look laparotomy and survival were somewhat more common in advanced-stage patients with diploid cancers than in those with aneuploid cancers. We conclude that ploidy of ovarian cancers can be determined using a computerized image analysis system to quantitate feulgen staining of cells in touch imprints. Ploidy is unlikely to play a role in treatment planning for patients with advanced-stage disease. Larger studies of patients with early-stage disease are needed, however, to determine whether ploidy is a more accurate means of predicting which patients are most likely to benefit from adjuvant therapy.     

Human papillomavirus genotype as a prognostic indicator in carcinoma of the uterine cervix

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only beginning to be appreciated. In this series of 100 women with cervical cancers analyzed for the presence of HPVs 6, 11, 16, 18, and 31 by Southern blot hybridization, a more aggressive clinical behavior was demonstrated for tumors containing HPV 18 than for those with HPV 16 or those in which no HPV was identified. Among 69 stage Ib tumors, no significant differences were found in the size of tumor, presence of parametrial involvement, or lymph node metastasis among patients whose tumor contained HPV 16, HPV 18, or no HPV DNA; however, 45% of the women with HPV 18-containing tumors (five of 11) had recurrence, as compared with only 16% of those with HPV 16 (five of 31) during the 20-month mean follow-up period. This tendency for HPV 18-containing tumors to recur was seen with all histologic subtypes of cervical cancers and with all grades of tumor. In addition, patients with HPV 18-containing tumors were more likely to give a history of recent normal Papanicolaou smears than were those whose tumors contained HPV 16. Forty-four percent of women with HPV 18 in their tumors had a history of three class I Papanicolaou smears in the 3 years before the diagnosis of cancer, whereas a similar history was elicited in only 16% of those with HPV 16 in their tumors, suggesting that HPV 18-containing tumors might progress to invasion without a prolonged preinvasive period.     

DNA aneuploidy is associated with increased mortality for stage I endometrial cancer

OBJECTIVE: The current study was undertaken to determine if DNA ploidy is a useful prognostic variable for predicting recurrence in stage I endometrial cancer. For cancer of the endometrium, survival following recurrence may depend on a number of factors, including the pattern of recurrence and the response to second line treatment. Previous studies have demonstrated a worse survival for patients with DNA aneuploid tumors. It remains unclear, however, whether this is necessarily due to a higher risk of recurrence. This study was undertaken to assess DNA ploidy and risk of recurrence in patients with stage I endometrial cancer. METHODS: This is a retrospective study of surgically treated patients with stages IB and IC endometrial cancer treated from 1992 to 2000. All patients underwent definitive surgery, including staging lymphadenectomy. None of the patients received postoperative treatment. DNA ploidy was determined using flow cytometry and image analysis. Grade, lymph-vascular space invasion, stage (stage IB versus IC), and DNA ploidy were analyzed with regard to recurrence and survival. RESULTS: There were 100 patients with stages IB and IC endometrial cancer in this analysis. There were 17 recurrences (17%) and 10 patients that died of cancer (10%). Grade 3 and the presence of lymph-vascular space invasion were associated with increased risk of recurrence; DNA aneuploidy and stage were not. Grade, lymph-vascular space invasion, and DNA ploidy were associated with survival. These findings indicate that DNA aneuploidy does not increase the risk of disease recurrence but is associated with overall survival. CONCLUSION: Although the recurrence risk is not higher for patients with surgical stage I endometrial cancer and aneuploid tumors, overall mortality remains higher.     

Analysis of ovarian tumors for the presence of human papillomavirus DNA

AIM: The role of human papillomavirus (HPV) infection in ovarian tumorigenesis is uncertain. The objective of this study was to screen a collection of ovarian tumors for the presence of high-risk oncogenic HPV types 16, 18 and 33. METHODS: Twenty benign and malignant ovarian tumors were obtained from women undergoing pelvic surgery at a regional comprehensive cancer institution in North America. DNA was isolated from the snap-frozen tumors, and commercial polymerase chain reaction (PCR) detection sets were used to analyze the tumor DNA samples for the presence of DNA from HPV types 16, 18 and 33. RESULTS: The DNA from HPV types 16, 18 and 33 was not detected in any of the ovarian tumors. CONCLUSIONS: Our findings do not support an association between infection with HPV types 16, 18 and 33 and ovarian neoplasia in this patient population.     

Quantitative nuclear DNA analysis of human ovarian adenocarcinoma: compared before and after chemotherapy and correlated with clinical response

Quantitative DNA measurements on 18 human ovarian adenocarcinomas were made by computerized image analysis. The DNA content of the tumor cells was measured on specimens of tumor obtained at the initial diagnostic surgery and at second-look surgery after treatment with chemotherapy. The mean DNA content of the specimens and the ploidy pattern of the tumor cells were determined. With the exception that borderline tumors had near normal ploidy patterns and mean DNA content, there was no consistent correlation between the stage of disease, grade, or histiologic character of the tumor and either the DNA content or ploidy pattern. But it was noteworthy that all three of the patients who had complete responses (negative second-looks), also had tumors with DNA content and ploidy patterns near triploid. When the ratio of mean DNA content before and after chemotherapy was determined for each ploidy group, there was an apparent correlation between this ratio and clinical status of the patient 10 month after chemotherapy. That is, patients with low ploidy tumors and high DNA content ratio (greater than 1.25) had a better prognosis than patients with high ploidy tumors and lower DNA content ratios (less than 1.25). Thus, although the mean DNA content of the tumor at the initial surgery was not in itself of sufficient prognostic value, when the mean DNA content of the tumor after chemotherapy is also known, an accurate picture of the patients clinical response could be determined.     

DNA-ploidy and HPV infection in epithelial lesions of the lower female genital tract

DNA content was related to the type of human papillomaviruses (HPV) in a series of 87 lesions of the lower female genital tract. Nineteen condylomas, 32 biopsies with slight dysplasia, 19 with moderate dysplasia and 17 with severe dysplasia-carcinoma in situ were studied. HPV status was assessed by in situ hybrization (ISH) with biotinylated probes (HPV 6/11, 16/18, 31/35/51) and the polymerase chain reaction (PCR) (HPV 16,18). DNA ploidy was measured by Feulgen DNA cytophotometry. Positivity for HPV by ISH and PCR was obtained in 48% and 59% of the biopsies, respectively. Seventy-eight per cent of the lesions were diploid or tetraploid and the remaining 22% were aneuploid. The percentage of aneuploid DNA increased with the severity of the lesions. By comparing DNA-ploidy and HPV types by ISH, diploid DNA was more frequently found in HPV 6/11 positive lesions (93%) than in HPV 16/18 positive (81%) or HPV 31/35/51 positive (57%). PCR was more sensitive for detecting HPV in aneuploid dysplastic lesions than ISH, probably indicating the HPV copies are scarce in such lesions. In summary, the results indicate some relationship between aneuploidy and HPV types 16/18 and 31/35/51, which supports an oncogenic potential of these subtypes of HPV.     

DNA ploidy and steroid receptors as predictors of disease course in patients with endometrial carcinoma

Prognostic factors for outcome of malignant disease should be based on objective assessments whenever possible, so that the results may be reproduced. In a prospective study, tumor samples from 75 patients were subjected to flow cytometric DNA analysis. Samples were also taken from 61 patients for estradiol and progesterone receptor measurements. The course of the disease was analysed with regard to ploidy and receptor status. Receptor status was significantly correlated with ploidy, as diploid tumors were more often receptor-positive or receptor-rich (greater than or equal to 30 fmol/mg protein). Mortality and recurrence rates were highest among patients with aneuploid or receptor-poor tumors. Ploidy, receptor status, histological grade, surgical stage, and myometrial invasion were found to be of significant prognostic value. By multivariate analysis, ploidy was indicated to be the best predictor, followed by surgical stage. DNA and receptor measurements are recommended in research on endometrial carcinoma, and may become useful in routine clinical work.     

Human papillomavirus genotype as a prognostic factor in carcinoma of the uterine cervix

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only now beginning to be appreciated. The objective of this study was to determine the clinical implications and prognostic value of the HPV genotype in cervical carcinomas. In this study, we employed an HPV DNA chip to detect the type-specific sequence of HPV from cervical swabs taken from women with biopsy-proven neoplastic lesions of the cervix. We divided the patients into four groups: HPV-negative, HPV-16-related, HPV-18-related, and intermediate risk type-related. Associations with clinicopathologic data (stage, histologic type, lymph node status, parametrial invasion, lymphvascular space invasion, tumor size, vaginal involvement) and overall survival were assessed. HPV DNA was detected in 81.4% of the patients, and 19.0% harbored multiple HPV variants. HPV-16-related was the predominant type and was detected in 47.4% (46/97) of the patients. The HPV-16-related types were detected more frequently in patients with squamous cell carcinomas, whereas the HPV-18-related types were more prevalent in cases of adenocarcinomas and adenosquamous carcinomas (P < 0.05). Otherwise, no significant correlations were detected between the HPV genotype and any other clinicopathologic parameters. After a median follow-up of 30 months, the 5-year survival rate was lower in the HPV-18-related patients, but this difference was not found to be statistically significant, according to the results of the log-rank test. We conclude that neither the presence nor type of HPV DNA bears any prognostic significance in cases of cervical carcinoma.     

Implications of human papillomavirus type for survival in cervical squamous cell carcinoma

In a Swedish series of 107 invasive squamous carcinomas of the cervix, DNA extraction from paraffin-embedded material was successful in 97 cases. The prevalence of human papillomavirus (HPV) in this material was 86.6%, as determined by polymerase chain reaction (PCR) using both consensus and type-specific primers. HPV type 16 was most common (42.3%; other types were 31 (12.3%), 18 (9.3%) and 33 (10.3%). Seventeen cases (17.3%) were positive for the consensus primers only and were regarded as HPV of unknown type. There was no significant difference in corrected survival between patients with HPV-positive or -negative tumors. In the HPV-positive group, patients with tumors containing HPV 33 or HPV 18 had a significantly poorer prognosis than patients with tumors containing other types of HPV DNA (relative hazard 3.18, 95% confidence interval 1.37–7.39, P = 0.007), implying a prognostic significance of HPV type.     

Effect of deoxyribonucleic acid ploidy status on survival of patients with carcinoma of the endometrium.

This retrospective study was performed to determine the clinical usefulness of deoxyribonucleic acid (DNA) ploidy and the amount of DNA in the nucleus of the tumor cell on the prognosis of patients with carcinoma of the endometrium. Five year follow-up study was obtained for 121 patients. Flow cytometric analysis was used to determine tumor cell ploidy from paraffin-embedded specimens. Patients were grouped according to ploidy, clinical stage and grade and whether or not they received postoperative radiation. The data were subjected to a Cox proportional hazards regression analysis, and only ploidy status and clinical stage were significantly associated with survival time. Of the 121 patients observed, 44.6 per cent were aneuploid and 55.4 per cent, euploid. Preliminary chi-square analysis indicated a strong survival advantage to those patients with euploid endometrial carcinoma. The over-all five year survival rate for patients with aneuploid tumors was 53.7 per cent, as opposed to 80.6 per cent for patients with euploid tumors (p less than 0.01). Eighty-seven patients were Stage I, 39 aneuploid, 48 euploid. The five year survival rate for patients with Stage I aneuploid was 71.8 versus 85.4 per cent for those who were euploid. Twenty-one patients were Stage II; seven aneuploid and 14 euploid. The five year survival rate for aneuploid patients was 14.3 versus 85.7 per cent for euploid patients. The over-all five year survival rate for those with Stage I and II was 85.5 per cent euploid and 63.0 per cent aneuploid, p less than 0.05. Patients with Stage III or IV had poor outcome regardless of ploidy status. These data show that patients with euploid Stage I and II carcinoma of the endometrium have a significant survival advantage over patients with aneuploid tumors. We, therefore, believe that ploidy status may be used to facilitate the determination of prognosis in carcinoma of the endometrium.     

Possible prognostic significance of human papillomavirus type in cervical cancer

While several different human papillomaviruses (HPV) have been associated with cancer of the cervix, it is yet to be determined if specific HPV types have clinical or prognostic significance. To address this question, 30 cases of invasive carcinoma (squamous carcinoma, adenosquamous carcinoma, and adenocarcinoma) with HPV DNA sequences detectable in the tissue were analyzed. HPV type was determined by Southern blot DNA hybridization. Clinical information was obtained by chart review, and all biopsy and surgical specimens were reviewed microscopically without knowledge of HPV type. HPV 16 was detected in 14 cases, HPV 18 in 6, and HPV 31 in 2. In eight samples there were distinctly different, but as yet uncharacterized, HPV DNAs. Of the factors evaluated, tumor grade was found to have a statistically significant relationship to HPV type. Eighty-three percent of HPV 18-associated tumors were grade 3 tumors (5 of 6) as compared to only 7% of HPV 16-associated tumors (1 of 14) (P = 0.002). Age at diagnosis and nodal status in relation to HPV type exhibited a trend but were not statistically significant. The mean age of the HPV 18 group was 37 years, compared to 49 years for the HPV 16 group. Similarly, among Stage IB cancers, nodal involvement was associated with 60% of HPV 18 cases (3 of 5) as compared with 36% of HPV 16 cases (4 of 11). These observations suggest that HPV 18 may be associated with a more aggressive form of cervical cancer than other HPV types.     

HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas

The present study was designed to analyze the relationship of human papillomavirus (HPV)-DNA, microvessel density, and their impact on clinical outcome in early cervical carcinoma. HPV-DNA was evaluated in 171 cases of cervical carcinoma treated from 1965 to 1990. In 110 cases, the analyses could be performed. A polymerase chain reaction technique was used on paraffin-embedded specimens obtained before the start of therapy. HPV-DNA of any type was detected in 78% (86/110) of all evaluable tumors. HPV16 was the predominant type and was detected in 56% (62/110), HPV18 in 8% (9/110), and HPV35 in 21% (23/110). Patients with tumors containing HPV16 or HPV18 were significantly (P = 0.011) younger than patients with tumors not containing either of these two subtypes. Vascular space invasion and lymph node metastases were observed more frequently in tumors expressing HPV16 and HPV18 (P = 0.002, P = 0.047) than in tumors negative for these HPV strains. Tumors containing HPV16 and HPV18 were significantly (P = 0.012) larger and more frequently (P = 0.005) associated with higher FIGO stages. The cancer-specific survival rate was lower for patients with HPV16- and HPV18-positive tumors, but the difference was not statistically significant. The microvessel density was a non-significant prognostic factor. The overall 5-year survival rate of the complete series was 91%. It was concluded that HPV-DNA was a prognostic factor in early-stage cervical cancer and was associated with the age of the patient, vascular space invasion, lymph node metastases, tumor size, and FIGO stage.     

Analysis of fine-needle aspirates for HPV by PCR may be useful in diagnosis of metastatic gynecologic malignancies

Human papillomavirus (HPV) DNA has been shown by molecular hybridization studies to persist in both recurrent and metastatic disease in tumors of the female genital tract. We report here the use of the polymerase chain reaction to identify HPV DNA in material from fine-needle aspirates (FNA) of recurrent or metastatic lesions to document the primary malignancy arising in the lower genital tract. Fine-needle aspirates of suspected recurrent or metastatic tumors were obtained from nine patients with carcinoma of the lower genital tract and five patients with malignancies that have not been associated with HPV. DNA was extracted from the FNA and tissue block, when available, and amplified with HPV 6, HPV 16, and HPV 18 specific primers. In eight of the nine tumors from the lower genital tract, HPV DNA was identified in both the primary and metastatic lesions. In every case the HPV genotype was identical. One cervical carcinoma and five non-HPV associated tumors were negative for papillomavirus DNA. This study demonstrates that molecular hybridization techniques can be useful in identifying the source of a metastasis and have the potential to diagnose the presence of metastatic disease by detecting HPV DNA even when the cytologic criteria are equivocal.     

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.     

Flow cytometric measurement of ploidy and proliferation in effusions of ovarian carcinoma and their possible prognostic significance

The cellular DNA pattern of ascites and pleural effusions from 81 patients with advanced ovarian carcinoma was prospectively studied by means of flow cytometric DNA analysis. The degree of ploidy and the proportion of S-phase values were correlated to histological differentiation, to status, and to the development of disease. According to DNA indices, the cell populations distributed in the diploid to peridiploid and in the tri-to tetraploid range. Aneuploidy was more frequently associated with poor degree of differentiation, with progressive disease, and with higher proportion of cells in S phase. Thus, although patients with stable disease had a significantly larger proportion of tumors with diploid DNA content, all except four patients were dead within a median survival period of 12 months. No correlation was observed between total survival period and ploidy; however a significantly shorter survival time was noted in patients whose ascites comprised cell populations with S-phase values exceeding 15%.