Flow-cytometric DNA analysis of early stage adenocarcinoma of the cervix.

OBJECTIVE: The purpose of this study was to determine the utility of DNA flow cytometry as a prognostic indicator for risk of recurrence and overall survival in patients with early stage adenocarcinomas of the uterine cervix. METHODS: DNA flow cytometry was performed to determine ploidy, DNA index, and proliferative index in 66 women with stages IB and IIA pure mucinous adenocarcinomas of the cervix treated by primary surgical therapy with radical hysterectomy and pelvic lymphadenectomy. Fifty-seven of 66 (86.3%) tissue samples were analyzable. Three sections were obtained from paraffin-embedded tissue blocks containing primary tumor. Flow-cytometric results, along with other known prognostic variables for risk for recurrent disease and survival, were analyzed using Cox regression proportional hazards model, and survival curves were generated by the Kaplan-Meier method. RESULTS: Of 57 interpretable samples, DNA ploidy patterns were 18 (27%) diploid, 8 (12%) tetraploid, and 31 (47%) aneuploid. Thirteen of 66 patients (20%) experienced recurrence with a median time to recurrence of 1.6 years. No significant correlation was noted between DNA ploidy and risk of recurrence (P = 0.429). Multivariate analysis confirmed that positive metastatic lymph nodes were associated with risk of recurrence (P < 0.001). In node-negative patients, a high proliferative index (S% + G(2)M% > 20%), measured as a continuous variable, was the only significant factor for tumor recurrence (P = 0.002). CONCLUSION: DNA ploidy does not predict a patient's risk for tumor recurrence; however, a high proliferative index value warrants further investigation as a potential prognostic indicator for risk of recurrent disease in patients with adenocarcinoma of the uterine cervix.     

Flow cytometric evaluation of epithelial ovarian cancer

We investigated the prognostic significance of deoxyribonucleic acid content and proliferative activity of tumor cell populations as measured by flow cytometry of the tumor specimens from 115 women with epithelial ovarian cancer. Deoxyribonucleic acid aneuploidy was found in 87 of 115 (76%) of these cancers with a mean deoxyribonucleic acid index of 1.6 and S-phase fraction of 14.7%. The S-phase fraction of the 28 (24%) diploid tumors was 7.0%. Deoxyribonucleic acid ploidy was significantly correlated with survival. S-phase fraction was significantly correlated with ploidy, residual tumor, histology, grade, ascites, time to recurrence, and survival. Diploidy versus aneuploidy were the best discriminating values for deoxyribonucleic acid index and an S-phase fraction of greater or less than 18% for that parameter. Multivariate analysis revealed stage, S-phase fraction, residual tumor, and grade to be independently associated with time to recurrence, and stage, age, S-phase fraction, and largest metastases were factors associated with survival. Deoxyribonucleic acid ploidy did not significantly improve either model. These results suggest that abnormalities of deoxyribonucleic acid content and the proliferative activity of tumor cell populations are reflective of their biologic activity.     

Prognostic factors of adenocarcinoma of the uterine cervix

OBJECTIVE: The prognostic importance of adenocarcinoma of the uterine cervix was investigated. Methods. One hundred ninety-three patients (144 had stage I disease, 41 stage II, and 8 stage III-IV) with invasive adenocarcinoma of the uterine cervix treated initially at the Aichi Cancer Center between 1964 and 1995 were studied. RESULTS: Of all the invasive cervical cancers, 8.8% were adenocarcinomas that had been increasing during the past decade. The overall 5-year survival for stage I was 88.8%, stage II 44.9%, and stage III-IV 0% In univariate analysis, the clinicopathological factors associated with overall survival and disease-free survival were age of patient, stage of disease, presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, tumor size, and intraperitoneal metastasis. Multivariate analysis performed in all cases identified the clinical stage of disease, the presence of nodal metastasis, number of lymph nodes involved, lymph-vascular space invasion, and tumor size as the independent risk factors for recurrence and survival. In the analysis of stage I disease, lymph node metastasis and tumor size were the significant prognostic factors, while lymph-vascular space invasion and tumor size were the factors in advanced disease. Tumor grade and histological type were not associated with recurrence and survival. CONCLUSION: These results suggested the association of lymph node metastasis with the prognosis of early stage adenocarcinoma of the uterine cervix and lymph-vascular space invasion with the advanced stage. Tumor size was an independent risk factor throughout all stages.     

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.     

Evaluation of cellular proliferative activity and DNA ploidy as a prognostic factor in breast cancer

BACKGROUND: In the past years, morphological indexes and kinetic parameters have been introduced to characterize breast cancer in order to select breast cancer patients for adjuvant therapy. The alterations of the proliferative activity of neoplastic cells and DNA ploidy may provide important information about the aggressiveness of the lesion and may be used as powerful prognostic factors. In fact, prognostic information based on the classic clinico-pathologic parameters such as histotype, stage and grade are no longer sufficient to select patients for long term follow-up. The aim of this study was to evaluate the malignant potential of neoplastic cells through the determination of modifications of the proliferative index and the evaluation of DNA ploidy. METHODS: Forty-five breast cancer patients, 32 to 80 years of age, were studied. Proliferative indexes and DNA ploidy, besides the other clinical-pathologic parameters have been evaluated. The proliferative index was assessed with the immunocytochemical determination of Ki67 and quantified with the CAS 200: 31 cases had a high proliferative index, 12 medium and 2 low. DNA ploidy was analyzed on cytologic preparations with static cytometry utilizing an image analyzer CAS 200: 13 cases were diploid, 32 non-diploid. RESULTS: A close relationship was found between Ki67 expression and DNA ploidy. In fact, lesions with a high proliferative index were all non-diploid, whereas, those with a low proliferative index were all diploid. Lesions with a medium proliferative index were 2 diploid and 1 non-diploid. Among the 45 cases, studied in a follow-up period of 36 months, 12 showed disease recurrence; 3 showed a medium Ki67 expression and were diploid, 9 a high Ki67 expression and were all non-diploid. CONCLUSIONS: In conclusion, proliferative indexes and DNA ploidy may be considered additional prognostic parameters which may potentially influence the clinical behaviour of breast cancer and may be utilized besides all the other clinico-pathologic data to assess these lesions.     

Expression of cyclooxygenase-2 in adenocarcinomas of the uterine cervix and its relation to angiogenesis and tumor growth

OBJECTIVE: The purpose of this study was to evaluate cyclooxygenase (COX)-2 expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and tumor growth. METHODS: Thirty-nine cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-COX-2. Microvessels were immunohistochemically labeled with an antibody to CD34. Computerized image analysis was used to evaluate microvessel density (MVD). The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and proliferative cells were visualized by staining with Ki-67 antibody. RESULTS: Twenty-eight tumors (71.8%) were classified as COX-2 positive. COX-2 expression correlated with FIGO stage (P < 0.01). Tumors expressing COX-2 had a significantly higher MVD and Ki-67 index than those that did not express COX-2 (P < 0.05). However, COX-2 expression did not correlate with the apoptotic index. In univariate long-rank analysis, COX-2 expression, MVD, and FIGO stage were associated with shortened survival. However, FIGO stage and MVD were the only independent prognostic factors by multivariate analysis. CONCLUSIONS: Our results suggest that COX-2 expression in cervical adenocarcinomas may contribute to tumor progression by increasing angiogenesis and cell proliferation.     

Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma

Abstract. Lundgren C, Auer G, Frankendal B, Moberger B, Nilsson B, Nordström B. Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.
The purpose of this study was to evaluate the prognostic impact of image cytometry DNA ploidy, MIB-1, and p53 in relation to clinicopathologic variables in 376 consecutive patients with endometrial carcinoma stages I–IV. Following primary treatment 358 patients were considered tumor-free. Relapses and tumor-specific deaths of these patients were noted. Image cytometry DNA ploidy ( n = 340) and expression of MIB-1 ( n = 318) and p53 ( n = 323) were studied. In univariate analysis, stage ( P < 0.001), histopathologic subtype ( P < 0.001), degree of differentiation ( P < 0.001), HRT ( P = 0.034), DNA ploidy ( P < 0.001), and p53 ( P < 0.001) were significant predictors of relapse. Patient age showed that the estimated mean risk of relapse increases with nearly 64% per decade in life ( P 0.003), and the MIB-1 expression with 21% per 10-unit increment ( P 0.004). In multivariate analysis, degree of differentiation, MIB-1, and p53 lost their prognostic capability. However, after stage and histopathologic subtype, image cytometry DNA ploidy was the strongest predictor of outcome and was of value in predicting the risk for relapse. The combination of DNA ploidy, MIB-1, and p53 expression was an even stronger predictor of relapse-free survival than the individual prognostic factors.     

The relationship between mutant p53 gene, DNA contents and conventional clinicopathological prognostic variables in cases with endometrial carcinoma

PURPOSE OF INVESTIGATION: To determine whether p53 expression and DNA ploidy are related to traditional prognostic indicators in patients with endometrial cancer. METHODS: Tumor material (n=136) was analyzed regarding flow cytometric DNA ploidy and immunohistochemical p53 expression. Pearson's correlation, Fisher's exact test, Cox's regression analysis and the Kaplan-Meier survival test were used, as appropriate. RESULTS: P53 overexpression and DNA ploidy were higher in patients with nonendometrioid histology, FIGO advanced stage, poor grade, positive peritoneal cytology, lymphovascular space invasion (LVSI) and lymph node involvement (LNI). Histologic subtype, stage, grade, LVSI, LNI, tumor recurrence and overall survival rate correlated with p53 and DNA ploidy. No association of depth of myometrial invasion and age with p53 and DNA ploidy was observed. P53 was related to DNA ploidy. Of the factors analyzed, histologic subtype and myometrial invasion were found to be most important independent determinants of recurrence. Utilizing survival as the endpoint for multivariate analysis, when considering p53 and DNA ploidy together, histologic subtype, stage, peritoneal cytology, LNI and DNA ploidy were independent prognostic indicators. CONCLUSION: p53 expression and DNA ploidy were related to histologic subtype, FIGO stage, grade, LVSI, LNI, peritoneal cytology, tumor recurrence and overall 5-year survival. As compared to p53, DNA ploidy was the stronger independent predictor factor for survival. Neither p53 nor DNA ploidy were significant independent factors for tumor recurrence when submitted to multivariate analysis in this study. However, since p53 or DNA ploidy were found to be significant factors in univariate analysis and were correlated with tumor recurrence, they could be useful factors in making prognoses.     

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 cytometry and prognostic implications in patients with solid tumors

Flow cytometric DNA content analysis is a rapid, quantitative method of determining the DNA ploidy status and proliferative index of a given tumor. Abnormal DNA content, or aneuploidy, has been recognized as a marker of malignancy and is present in about 70 per cent of solid tumors. In the majority of solid tumors, the consensus is that the presence of an aneuploid tumor predicts a poorer over-all survival rate and a shorter disease-free interval, indicating that patients with diploid tumors have a more favorable prognosis than those with aneuploid tumors. The prognostic implications of an abnormal DNA content, therefore, suggest either a higher risk of relapse, a worsening of survival rate or a risk for progression of disease in stages I and II carcinoma of the breast, carcinoma of the colon and rectum, superficial carcinoma of the bladder and malignant melanoma. Thus, the assessment of cellular DNA content should be regarded as an additional prognostic determinant and should play an ancillary role in the decisions regarding the management of patients with malignant disease. With the introduction of more sophisticated technology, it will be possible to simultaneously assay for DNA ploidy and cell cycle distribution in addition to a series of tumor markers, such as CEA, and various products of oncogenes, thus providing further understanding of the heterogeneity of solid tumor cells.     

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.     

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.     

Prognostic factors of stage Ib cervical carcinoma treated by radical abdominal hysterectomy.

From 1982 to 1984, 189 patients with stage Ib carcinoma of the uterine cervix underwent radical abdominal hysterectomies as primary treatment at Chang Gung Memorial Hospital. Of these patients, six were lost to follow-up. Nineteen of the 183 patients with regular follow-up recurred at intervals of from 9 to 55 months. An assessment of prognostic factors was made by reviewing the chart and pathological findings and correlating them with the patient's present status. Using univariate analysis, bulky tumor size was found to bear the greatest risk of tumor recurrence. Six of the 15 patients (40%) with a diameter of more than 4 cm recurred. The other risk factors included parametrial involvement, histologic type of adenosquamous or adenocarcinoma, lymph node metastasis, poor differentiation, deep cervical stromal invasion, and lymphatic or vascular space invasion. In conclusion, analysis of prognostic factors identified a group of patients at high risk of recurrence and decreased survival, for whom prospective trials of adjunctive treatment should be considered.     

Small cell carcinoma of the cervix: a clinical and flow-cytometric study.

The clinical course of 14 patients diagnosed with small cell carcinoma of the cervix (SCC) was reviewed and compared to that of 37 cases of undifferentiated large cell nonkeratonizing carcinoma (LCNK). We observed the following differences between the two: SCC patients had a higher incidence of pelvic wall involvement and distant metastasis; the development of progressive disease was more frequent in SCC than in LCNK patients; median survival time was 9 months in SCC and 40 months in LCNK patients; flow cytometry revealed aneuploidy in all SCC and in 30% of the LCNK patients; the mean DNA index was 2.24 in SCC, significantly higher than in LCNK (1.15). DNA index in cases of SCC was related to survival time. SCC of the cervix is an extremely aggressive tumor, even when compared to other undifferentiated cervical cancers. Aneuploidy is a consistent feature and thus helpful for diagnosis. Due to the wide range of values, the DNA index cannot be used for diagnostic purposes, but it is of prognostic importance in SCC cases.     

Nuclear morphometry and DNA flow cytometry as prognostic methods for endometrial carcinoma

In a series of 227 women with endometrial carcinoma stages I–IV the prognostic value of nuclear morphometry and DNA analysis was evaluated prospectively. The tumors were also classified according to histologic subtype, degree of differentiation (FIGO), and nuclear grade. The DNA analysis (ploidy and S-phase fraction) was made using flow cytometry on fresh-frozen tissue. The morphometric measurements and the grading of the tumors were done on both fresh-frozen tissue and on formalin-fixed and paraffin-embedded tissue. The rate of recurrence for the complete series was 14% with 2.2% vaginal metastases. The overall 5-year survival rate was 68% and the corrected survival rate 76%. The minimum nuclear diameter and the standard deviation (SD) of the maximum nuclear diameter were significant and independent prognostic variables in a Cox multivariate analysis when analyzed on paraffin-embedded tissue. The nuclear grade was the single most prognostically informative variable. A corresponding analysis on fresh-frozen tissue showed that the S-phase fraction and the FIGO grading of the tumor were significant variables. The morphometric variables and the nuclear grading were non-significant prognostic variables. Morphologic changes in tumor cell nuclei during the freezing and thawing procedures may explain the loss of prognostic information. A combination of DNA index (fresh-frozen tissue) and the mean values of the shortest nuclear diameter and the SD of the longest diameter (paraffin-embedded tissue) gave the best prognostic information vis-a-vis cancer-related death in an all-possible-subsets regression analysis.     

Flow cytometric analysis of DNA ploidy and S-phase fraction of Stage IIIB cervical carcinoma

OBJECTIVES: To evaluate the role of flow cytometry-measured DNA ploidy and S-phase fraction as survival prognostic indicators in women with FIGO Stage IIIB squamous cell carcinoma of cervix. METHODS: We retrospectively reviewed the medical and pathological records of women with Stage IIIB squamous cell cervical carcinoma treated between 1993 and 1996. Flow cytometric analysis of DNA ploidy and S-phase fraction was performed by the modified Hedley technique using paraffin-embedded tissue. Survival was calculated using the Kaplan-Meier life-table analysis. RESULTS: Of the 75 cases, 66 were analyzable. Diploid tumors were found in 73%. The mean S-phase fraction was 14% (SD = 5.4). The overall 5-year survival rate was 60%. The survival of patients with aneuploidy tumors was significantly worse than that of the diploid tumors (p = 0.001). The survival of the patients who had S-phase fraction > 12% was significantly worse than those who had S-phase fraction < or =12% (p = 0.04). CONCLUSIONS: In this homogeneous study population, we found that aneuploidy and S-phase fraction >12% correlated with poor survival. Identifying this poor prognostic group would be of benefit in considering additional treatment for a better outcome.     

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.     

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.     

鳞状细胞癌抗原与子宫颈鳞状细胞癌的临床病理特征及预后的关系

目的 探讨治疗前血清鳞状细胞癌抗原（SCCAg）滴度与宫颈鳞状细胞癌（鳞癌）临床病理特征的关系,以及作为预测预后的因素的意义。方法 选择114例治疗前检测过血清SCCAg并经治疗后长期随访的Ⅰb1～Ⅱa期宫颈鳞癌患者,结合临床资料对SCCAg与临床病理特征及预后的关系进行单因素和多因素分析。结果 单因素分析显示,治疗前血清SCCAg滴度升高（正常值≤1．5mg／L）与肿瘤直径、深肌层浸润及盆腔淋巴结转移相关（P〈0．05）;多因素分析显示,SCCAg滴度升高与深肌层浸润（P=0．029）、盆腔淋巴结转移（P=0．049）相关。114例患者的5年累积无瘤生存率为78．6％,总复发率为27．2％。单因素分析显示,SCCAg滴度升高、盆腔淋巴结转移与5年累积无瘤生存率及复发相关（P〈0．05）;多因素分析显示,影响预后的独立因素为SCCAg滴度升高（P=0．030）和盆腔淋巴结转移（P=0．003）,影响复发的显著相关因素为盆腔淋巴结转移（P=0．006）。盆腔淋巴结转移且SCCAg滴度正常者与盆腔淋巴结转移且SCCAg滴度升高者,5年累积无瘤生存率（分别为50．0％、50．9％）、复发率[分别为60．0％（6／10）、47．1％（8／17）]、局部复发率[分别为3／8、20．0％（3／15）]和远处复发率[分别为1／8、20．0％（3／15）]分别比较,差异均无统计学意义（P〉0．05）。盆腔淋巴结无转移且SCCAg滴度正常者与盆腔淋巴结无转移且SCCAg滴度升高者,5年累积无瘤生存率（分别为98．0％、71．8％,P=0．003）、复发率[分别为9．8％（5／51）、33．3％（12／36）,P=0．006]、局部复发率[分别为2．1％（1／47）、26．5％（9／34）,P=0．001]分别比较,差异均有统计学意义。结论 治疗前血清SCCAg滴度升高和盆腔淋巴结转移是影响Ⅰb1～Ⅱa期宫颈鳞癌患者预后的独立因素。治疗前血清SCCAg滴度升高且盆腔淋巴结无转移患者的局部复发风险显著升高。     

An Evaluation of Prognostic Factors in Uterine Carcinosarcoma

The traditional clinical and histopathological prognostic variables and DNA ploidy were analyzed in 46 patients with histologically verified uterine carcinosarcoma. Twenty-three tumors were of the homologous and 23 of the heterologous type. Evaluable flow cytometric DNA histograms from paraffin-embedded tumor tissue were obtained in 39 patients. The overall 5-year cancer related survival was 31%. All tumors were of high malignancy grade. In univariate analysis of survival, extrauterine spread of tumor (P= 0.007), age (P= 0.008), and tumor diameter (P= 0.04) obtained statistical significance. Tumors with components of serous or clear cell carcinomas had a less favorable prognosis (P= 0.017). There was no difference in survival between patients with homologous and heterologous tumors (P= 0.39). Mitotic count, vessel invasion, and DNA ploidy did not obtain prognostic significance. In Cox multivariate analysis, extrauterine spread of tumor (P= 0.004) and age (P= 0.004) were found to be the most important prognostic factors followed by content of serous or clear cell carcinoma components (P= 0.027).