Mammographic Density in Women on Postmenopausal Hormone Replacement Therapy

Background . Fine-needle aspiration (FNA) biopsy has been used increasingly in the diagnosis and biologic characterization of breast carcinomas in patients who receive preoperative chemotherapy. Because proliferative activity of breast carcinoma has been shown to be of prognostic significance, the authors compared immunocytochemical Ki-67 growth fraction and flow cytometric S-phase fraction (SPF), both evaluated on FNA samples. Methods . The proliferative activity of 134 FNA samples from primary breast carcinoma patients was studied using both immunocytochemistry with the monoclonal antibody Ki-67 and SPF determined by DNA flow cytometry. Results . Ki-67 and SPF were evaluable in 114 and 107 cases, respectively, and both were evaluable in 95 cases. Of the 134 FNA samples studied, 37% were diploid and 63% were aneuploid. The distribution of both Ki-67 and SPF was different in diploid and aneuploid tumors. The median Ki-67 value as well as the median SPF were significantly higher in aneuploid versus diploid tumors (p < 0.001). Median Ki-67 and SPF values were used to discriminate between low versus high proliferating tumors. The overall concordance between Ki-67 and SPF was 75% (p < 0.001). A good correlation was found between Ki-67 and SPF (correlation coefficient = 0.72; p < 0.001). Conclusions . The results of the current study suggest the Ki-67 growth fraction and SPF determined by FNA may be used as measurements of the proliferative activity of breast carcinoma. The authors recommend these determinations be used as preoperative procedures in patients with a cytologic diagnosis of breast carcinoma who are candidates for neoadjuvant chemotherapy and/or endocrine therapy.     

Expression of MIB-1, mitotic index and S-phase fraction as indicators of cell proliferation in suerficial bladder cancer

Cell proliferation of transitional cell bladder cancer (TCC) was determined by MIB-1 immunolabeling, volume-corrected mitotic index (M/V index) and S-phase fraction measurement in 207 patients with superficial (Ta-T1) bladder cancer. The results were compared to T category, WHO grade and DNA-ploidy. The MIB-1 score was related to T category (P<0.001), WHO grade (P<0.001), DNA ploidy (P<0.0001), M/V index (P<0.0001) and fraction of cells in S phase (P<0.0001). The mean MIB-1 score was 6.37% for G1, 14.59% for G2 and 28.59% for G3 carcinomas (P<0.001). The MIB-1 score for Ta tumors was 9.24% and for T1 tumors 25.34% (P<0.001). The M/V index was 3.9 for G1, 11.5 for G2 and 25.9 for G3 tumors (P<0.0001). The M/V index for Ta tumors was 6.4 and 25.3 for T1 tumors (P<0.0001). WHO grade 1 tumors had 7.7%, grade 2 tumors 13.8% and grade 3 tumors 21.8% of cells in S phase (P<0.001). Of grade 1 tumors, 97% were diploid and 3% aneuploid, and 78% of grade 2 tumors were diploid and 22% aneuploid. Of grade 3 tumors, 30% were diploid and 70% aneuploid (P<0.001). Of Ta tumors, 92% were diploid and 8% aneuploid, respectively, whereas 40% of T1 tumors were diploid and 60% aneuploid (P<0.0001). The results show that quantitative cell proliferation indices are associated with T category and WHO grade in superficial bladder cancer. The prognostic value of the S-phase fraction and mitotic index has been demonstrated in several previous analyses of prognostic factors while the value of MIB-1 score on bladder cancer prognosis remains to be established in further follow-up studies.     

Measurement of cellular proliferation in human prostate by AgNOR,PCNA, and SPF

Tumor differentiation and proliferative activity are important predictors of biological behavior. While routine histological evaluation is fairly adequate to assess differentiation, tumor proliferative activity is difficult to measure. Silver staining for nucleolar organizer regions (AgNORs) is reported to be helpful for assessing tumor proliferation. We investigated the AgNOR counts in 20 formalin fixed, paraffin embedded human prostate tissues in three microscopic fields of 330X, using an image analysis system. A total of 200–700 nuclei were evaluated on histologically controlled areas of nonneoplastic prostate tissue, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma. The values were compared to flow cytometrically obtained synthesis phase fractions (SPF) and immunohis-tochemically semi-quantitated, proliferative cell nuclear antigen (PCNA) patterns. AgNOR counts were also compared to tumor stage and Gleason's score. The pattern of PCNA staining in formalin fixed specimens was widely variable, probably due to differences in preservation of antigen. The positive counts varied from 0 to 55%, with a mean value of 8.55 ± 15.9. The SPF values ranged from 5 to 13% with a mean value of 8.50 ± 2.37. Two of 20 tumors were aneuploid and 18 were of diploid range. The mean AgNOR values in nonneoplastic nuclei (1.836 ± 0.299), PIN (3.129 ± 0.295), and invasive tumor cell nuclei (4.737 ± 0.369) were highly significant (P < 0.0001) when paired differences were compared. AgNOR counts correlated significantly with tumor Gleason's score (P < 0.0145). However, the correlation coefficient for SPF and AgNOR values was not significant (P > 0.24), possibly because of the small number of samples examined. The highest AgNOR counts were found in the two aneuploid tumors. We conclude that AgNOR count may be a potential indicator of cellular proliferation, and possibly a marker of tumor differentiation. © 1993 Wiiey-Liss, Inc.     

Cytogenetic Abnormalities of Primary Breast Carcinoma: Comparative Analysis of Fluorescence In Situ Hybridization (FISH) and Flow Cytometry

Abstract: Breast cancer is a heterogeneous disease that is frequently associated with genetic alterations. Nonrandom chromosomal changes are assumed to play a role in breast tumorigenesis and progression. These changes can be detected by standard cytogenetics, which is technologically cumbersome, or by flow cytometry, which only provides a general overview of genetic alterations by ploidy status. Alternatively, fluorescence in situ hybridization (FISH) is a recently developed technique that has the capability to detect chromosomal changes in individual nuclei with preserved morphology of breast cancer. Our study was designed to investigate the molecular cytogenetic basis of nonrandom chromosomal aberrations in breast carcinoma by FISH and compare this data with flow cytometry. Large paraffin sections and 5 μm sections of 57 cases of invasive ductal carcinoma and 5 normal control samples were subjected to ploidy analysis by standard flow cytometry and FISH. By flow, 27 (47.4%) cases were aneuploid; while 30 cases were diploid. FISH, performed using a panel of six α-satellite centromeric probes for chromosomes 1, 7, 8, 11, 17, and X, detected 37 (64.9%) aneuploid tumor, while 20 tumors were diploid. Vast intratumor heterogeneity (75%) occurred in 27 of the 37 aneuploid tumors. FISH also identified aneuploidy in 50% of cases that were interpreted as diploid by flow. The FISH and flow results were concordant in 15 diploid cases and 22 aneuploid cases, yielding an overall agreement of 64.9%. This agreement was significant above that expected by chance (kappa = 0.309, p = 0.007). Sensitivity and specificity of FISH for aneuploidy detected by flow were 81.5% and 50.0%, respectively. Discordant FISH aneuploid tumors were characterized by gain or loss of 1-3 chromosomes. Normal controls were consistently diploid by both flow and FISH. Our data suggest that FISH is more sensitive in detecting aneuploidy than flow cytometry and provides valuable genetic data of breast cancer cells.     

Characterization of squamous cell bladder tumors by flow cytometric deoxyribonucleic acid analysis: a report of 100 cases

We studied 100 cases of squamous cell carcinoma of the bladder by flow cytometry after cystectomy. Tumors were classified according to the deoxyribonucleic acid profile into diploid or aneuploid. Proliferation of the tumors was assessed from the proportions of S-phase cells. The flow cytometric data were correlated to the histopathological stage and grade. Grade 1 tumors could be subdivided into diploid and aneuploid in 60 and 40% of the cases, respectively, while 95% of the grade 2 and all grade 3 tumors were aneuploid. Diploid tumors had low proliferation rates, while aneuploid tumors had significantly higher values. A high frequency of muscle invasive diploid squamous cell tumors was noted. Tumor heterogeneity was studied by comparing cell material from superficial and deep tumor areas, which were in agreement in 77% of the cases. By comparing biopsy material with that obtained by bladder washings, biopsy material yielded better information regarding deoxyribonucleic acid ploidy in half of the aneuploid tumors. These results indicate that flow cytometry offers an additional objective method to characterize squamous cell carcinoma.     

Ploidy disturbance of normal-appearing bladder mucosa in patients with urothelial cancer: relationship to morphology

A total of 4 patients with transitional cell carcinoma of the bladder underwent complete mapping of the mucosa and tumors with combined cytologic, histologic and flow cytometric evaluation of the extent of involvement of the neoplastic process. Flow cytometric measurement of the cellular deoxyribonucleic acid content in multiple cell samples taken at cystoscopy showed similar changes in the normal mucosa as in the tumors. These changes consisted of an increased fraction of cells with S-phase deoxyribonucleic acid content in 2 patients with grades 1 and 2 tumors, and the presence of extensive aneuploidy in 2 patients with World Health Organization grades 2 and 3 tumors. While grade 1 and some grade 2 tumors (World Health Organization) are composed only of diploid cells, some of the grade 2 and all grade 3 tumors consist of a mixture of diploid and aneuploid populations. Such aneuploid clones could be identified in normal-appearing mucosa and, thus, be a source of new occurrences. The impression of heterogeneity in histograms from different tumors within the same bladder is assumed to be caused by a variation in the ratio between aneuploid and diploid populations (high ratio in tumor and low in normal-appearing mucosa). This phenomenon may be the reason for variation in grading based on histological studies.     

DNA Flow Cytometry in Surgically Treated Lung Cancer: Prognostic Significance

Although DNA aneuploidy and high proliferative activity (S-phase fraction, SPF) of tumour cells, measured by flow cytometry, have proved to be indicators of poor prognosis in most solid tumours, there have been conflicting results in lung cancer studies. During a four-year period we studied the prognostic significance of DNA ploidy and SPF in 99 surgically treated lung cancer patients. Flow cytometric analysis was done from archival, formalin-fixed, paraffin-embedded tumour specimens. DNA index and SPF were determined, using MultiCycle software with sliced nuclear correction to compensate for debris. There were 61 DNA diploid and 38 DNA aneuploid tumours. The median SPF was 10.2%. Neither ploidy nor SPF was associated with previously known prognostic factors. Survival was poorer in patients with aneuploid tumours than in the other patients, but the difference was not statistically significant. DNA ploidy and SPF thus do not seem to be useful prognostic indicators in surgically treated lung cancer.     

DNA flow cytometry in surgically treated lung cancer--prognostic significance.

Although DNA aneuploidy and high proliferative activity (S-phase fraction, SPF) of tumour cells, measured by flow cytometry, have proved to be indicators of poor prognosis in most solid tumours, there have been conflicting results in lung cancer studies. During a four-year period we studied the prognostic significance of DNA ploidy and SPF in 99 surgically treated lung cancer patients. Flow cytometric analysis was done from archival, formalin-fixed, paraffin-embedded tumour specimens. DNA index and SPF were determined, using MultiCycle software with sliced nuclear correction to compensate for debris. There were 61 DNA diploid and 38 DNA aneuploid tumours. The median SPF was 10.2%. Neither ploidy nor SPF was associated with previously known prognostic factors. Survival was poorer in patients with aneuploid tumours than in the other patients, but the difference was not statistically significant. DNA ploidy and SPF thus do not seem to be useful prognostic indicators in surgically treated lung cancer.     

Proliferative activity assessed on the basis of DNA ploidy patterns in primary lung cancer

Flow cytometric cellular DNA-RNA content analysis by acridine orange staining was conducted on surgical fresh specimens of primary lung carcinomas from 66 patients (31 squamous cell carcinomas, 34 adenocarcinomas and 1 large cell carcinoma). The frequency of aneuploid tumors was 84.6% among the tumors. RNA content (RNA Index) in the DNA aneuploid tumor much more significantly (p less than 0.05) increased than the DNA diploid tumor. Tumor doubling time in the DNA aneuploid tumor was significantly (p less than 0.05) shorter than in the DNA diploid tumor. In the patients with lung cancers that recurred within 1 years, recurrence of the DNA aneuploid tumor was higher than the DNA diploid tumor. It is evident from the above results that proliferative activity in the DNA aneuploid tumor increases much more than in the DNA diploid tumor. This in turn may induce early recurrence in patients with lung cancer.     

Importance of cellular DNA content in pre-malignant breast disease and pre-invasive carcinoma of the female breast

The risk of malignant change in pre-invasive breast disease such as proliferative atypia (PA) or the risk of invasive carcinoma arising from ductal carcinoma in situ (DCIS) remains uncertain in individual women because of the absence of any prognostic criteria. In order to clarify this, the cellular DNA content (ploidy) of 51 screen-detected lesions has been investigated. Cellular DNA measurements were made by static cytometry following Feulgen staining of disaggregated tissue sections and the resulting histograms classified as either diploid or aneuploid. Thirteen cases of PA and twelve of DCIS were compared with twenty-six biopsies showing DCIS with adjacent invasive carcinoma (DCIS + Ca). In the latter group, ploidy of the invasive carcinoma was compared with the associated DCIS in 16 cases. Aneuploid cells were found in approximately 30 per cent of PA and DCIS lesions but in 23 of 26 cases of DCIS + Ca. Of 16 assessable cases of co-existing DCIS and micro-invasive carcinoma both were aneuploid in 11, both diploid in 1, and in 4 cases the DCIS was aneuploid whereas the invasive carcinoma was diploid. These results suggest that aneuploidy may be of value in predicting the most biologically aggressive of these pre-invasive lesions.     

DNA ploidy and S phase fraction in human bladder cancer. Relation to survival and histological grade (WHO)

The nuclear DNA content of archival paraffin-embedded bladder cancer samples (70 patients) of WHO grades I-III has been measured by flow cytometry. The female/male ratio was 15/55. The mean follow-up time was 13 years (range 9.6-22.0 years). 37 of 70 (53%) patients had DNA index 1.0 (diploid DNA content), and the remaining 33 (47%) patients had an aneuploid tumor. There was no significant difference in the age (mean +/- SD) of the patients having a diploid (66 +/- 9 years) or an aneuploid tumor (68 +/- 11 years) at the time of diagnosis. 47 deaths occurred during the follow-up period; 24 (51%) of these were due to bladder cancer (12 diploid, 12 aneuploid tumors). No significant difference was found after radical treatment during the disease-free interval (mean +/- SD) between diploid (48 +/- 45 months) and aneuploid (35.5 +/- 35 months) groups of patients. Recurrences during the follow-up period were equally common among aneuploid and diploid tumors. A statistically significant relation between histological grade and survival could be demonstrated, but DNA ploidy and S phase fraction had little prognostic value in this respect. There was no statistically significant difference in survival between aneuploid (30%) and diploid (35%) groups of tumors during the follow-up period. The study suggests that flow cytometric determination of nuclear DNA ploidy from paraffin-embedded samples in bladder tumors does not add to the prognostic power of subjective histological grading.     

Analysis of flow cytometric nuclear DNA content of the thymoma and its relationship to malignant intensity

Determination was made of the nuclear DNA content of paraffin-embedded specimens of resected thymoma using flow cytometry in 39 patients. Relationships among nuclear DNA content, clinicopathological findings and prognosis were studied. The frequency of DNA aneuploid tumors was 30.8%, 6.7% in stage I (15 patients), 28.6% in stage II (7 patients), 44% in stage III (9 patients) and 62.5% in stage IV (8 patients) according to Masaoka's classification, indicating more in increase with advancing stage and significant (p less than 0.05) more increase invasive thymoma than in noninvasive thymoma. The 5 year and 10 year survival rates of DNA diploid tumors were each 94%, while DNA aneuploid tumors, 75% and 45%. Patients with DNA aneuploid tumors showed less favorable prognosis than those with DNA diploid tumors. Similar results were found in patients with invasive thymoma and in those on whom subtotal or partial resection were performed. The present results indicate DNA aneuploid tumors to have greater malignant intensity than DNA diploid tumors in resected thymoma. Flow cytometric nuclear DNA content analysis provides useful biological data and new indices for evaluating the malignancy of resected thymoma.     

Flow cytometric cell cycle analysis using a monoclonal antibody to bromodeoxyuridine on gastric cancers

Flow cytometric cell cycle analysis using a monoclonal antibody to Bromodeoxyuridine was performed on 117 gastric cancers. Dissociated cells were stained with indirect immunostaining for BrdU (FITC-BrdU) and propidium iodide. Bivariate BrdU/DNA distribution were obtained using EPICS-C flow cytometry. Tumor ploidy was classified as follows, D1: diploidy, D2: diploidy + aneuploidy, A1: single aneuploidy, A2: multiple aneuploidies. The ploidies of noncancerous gastric mucosa were all diploidy and that of S-phase fraction(SPF) were ranged from 0.0% to 1.2%. In 117 gastric cancers, aneuploidy was observed in 80 cases, D2: 38, A1: 15, A2: 27. SPF was higher in aneuploidy (14.5 +/- 5.1%) than diploidy (6.1 +/- 5.1%). Significant differences were observed between that of D1 (6.1 +/- 2.5) and D2 (13.6 +/- 6.2), A1 (12.5 +/- 4.5), A2 (16.0 +/- 3.2), and A1 and A2 (p less than 0.01). The patients with aneuploid tumors had poor prognosis than diploid tumors (p less than 0.05). In concerned with DNA ploidy pattern, the patients with A2 had most poor prognosis than the other (p less than 0.05). Furthermore, the patients with SPF over 10% had poor prognosis than that of SPF below 10%. These results indicated that DNA ploidy pattern and SPF may possibly be useful prognostic markers for gastric cancers.     

DNA ploidy, S-phase fraction and cytomorphometry in relation to survival of human penile cancer.

The prognostic significance of DNA ploidy, DNA index, S-phase fraction (SPF) and median nuclear size was studied in 11 patients with squamous cell carcinoma of the penis. These patients have been followed for a minimum of 7 months after diagnosis. Nuclear DNA content was determined by flow cytometry from paraffin-embedded tissue. Patients with DNA diploid cancer (n = 7, 64%) had a better survival rate than patients with aneuploid cancer, and a small SPF was associated with a favorable outcome. A statistically significant relation between median nuclear size and survival could be demonstrated. Small modal nuclear size associated with poorer prognosis. There was a significant difference in survival between metastatic and nonmetastatic groups of tumors during the follow-up period. This study suggests that flow cytometric determination of nuclear DNA ploidy from paraffin-embedded samples in penile cancer does add an additional prognostic determinant in addition to the clinical staging of tumors.     

Value of nuclear DNA ploidy patterns in patients with prostate cancer after radical prostatectomy.

Flow cytometric analysis of DNA ploidy was performed on prostatic adenocarcinoma specimens from 80 patients. In all these patients a radical retropubic prostatectomy had been performed. The nuclei for DNA ploidy determination were extracted from paraffin-embedded material of whole sections of the prostate from patients treated by radical prostatectomy between 1980 and 1985. DNA ploidy was a strong prognostic indicator independent of tumor grade and tumor stage. DNA ploidy offered additional information on both tumor stage and tumor grade. In stage C disease the likelihood of progression-free survival was 89.5% in diploid tumors and 27.8% in aneuploid tumors after 9 years. In tetraploid tumors all patients progressed after 9 years. The computed survival rates in stage C disease showed that patients with diploid tumors did significantly better than those with aneuploid or tetraploid tumor patterns. These data indicate therefore that DNA ploidy patterns determined by flow cytometric analysis provide important additional prognostic information on prostatic adenocarcinoma treated by radical prostatectomy.     

The importance of DNA flow cytometry in node-negative breast cancer

DNA flow cytometric analysis and conventional clinical factors were compared with disease outcome in 257 patients with node-negative infiltrating ductal carcinoma who had been treated between 1976 and 1983. Median follow-up was 80 months; none of the patients received adjuvant therapy. The relative prognostic importance of clinical variables, ploidy, and S-phase fraction was analyzed by Cox multivariate analysis. Ploidy was analyzable for 198 tumors and did not predict survival. Nuclear grade predicted disease-free survival for all patients. For 71 patients with diploid tumors, only high S-phase had a statistically significant association with relapse. For 127 patients with aneuploid tumors, tumor diameter predicted both disease-free survival and cancer death; histologic grade was also significant for predicting disease-free survival. In conclusion, flow cytometric determination of ploidy and S-phase fraction can provide valuable predictive information in node-negative breast cancer in addition to conventional variables.     

DNA Ploidy is an Independent Predictor of Survival in Breast Invasive Ductal Carcinoma: A Long-term Multivariate Analysis of 393 Patients

Purpose

To evaluate “classic” prognostic parameters, as well as DNA ploidy and S-phase fraction (SPF), in relation to disease-free (DFS) and disease-specific (DSS) survival in breast invasive ductal carcinoma (IDC) with long-term follow-up study.

Methods

The study involved 393 patients with IDC and median follow-up of 134 months (50–240). Histological grading, tumor size, axillary nodal involvement, pathological staging and hormone receptor status were considered as established prognostic markers. Ploidy and SPF were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables.

Results

There were 105 (26.7 %) deaths and 140 (35.6 %) disease recurrences during follow-up. Two hundred thirty-one (58.8 %) tumors were aneuploid. High SPF and aneuploidy were associated with tumors with higher grade of differentiation, greater size and negative hormone receptors. Higher SPF and advanced disease stage are correlated. In univariate analysis, all the clinicopathological and cytometric features, including patients <40 years and a subgroup presenting hypertetraploid/multiploid tumors, are significantly correlated with clinical outcome, apart from SPF and estrogen receptors for DFS. In multivariate analysis, nodal involvement, DNA aneuploidy and lack of progesterone receptors (for DSS) retained statistically significant association with shorter survival. In node-negative patients, ploidy (for DFS) and estrogen receptors (for DSS) significantly predicted survival. In both subgroups of node-positive patients and those (n = 195) with intermediate differentiation tumors (G2), aneuploidy was an indicator of worse prognosis.

Conclusions

Along with nodal status and hormone receptor expression, DNA ploidy is an independent predictor of long-term survival in IDC.     

Flow cytometric analysis of DNA content and proliferation and immunohistochemical staining of Ki-67 in non-small cell lung cancer.

BACKGROUND: The aim of our study was to examine the significance of tumour DNA-content and proliferation in lung cancer. METHODS: The DNA content and S-phase fraction (SPF) was determined by flow cytometry in 125 resected tumours of patients with non-small cell lung cancer. In 40 cases we compared the SPF with immunohistochemical staining of the Ki-67 protein using MIB-1 antibody. RESULTS: DNA aneuploidy was detected in 84.8% (106/125). Cell cycle analysis for the determination of proliferation activity was only possible in 69 (55.2%) cases. An SPF of 0-8% as a sign of low proliferation was found in 27 specimens. In advanced tumours at stage III and IV the proportion of tumours with SPF 9-16% was significantly (p<0.05) increased as compared to tumours at stage I and II. There was a significant correlation (p=0.012, ascent: 0.045) between SPF and MIB-1. Patients with aneuploid tumours had a relative risk of 1.4 to die earlier than patients with diploid tumours. Patients with SPF of 9-16% in the tumour tended to decreased survival (5-year survival rate: 29%) in correlation to patients with a percentage of SPF 0-8% (5-year survival rate: 38%, p=0.5). These differences were significant (p=0.048) in patients with adenocarcinomas only. In the multivariate COX-regression model age (p=0.03) and stage (p=0.0001) were significant prognostic factors, ploidy state (p=0.33) was of no prognostic significance. CONCLUSIONS: Flow cytometry seems to be a useful method for understanding the clinical behaviour of lung cancer. Especially the SPF in adenocarcinomas may be used as a prognostic indicator.     

Flow cytometric analysis of deoxyribonucleic acid ploidy and proliferation in choroid plexus tumors.

The deoxyribonucleic acid (DNA) content of 10 choroid plexus tumors, including 4 malignant tumors and 3 normal choroid plexus controls, was analyzed by flow cytometry to determine whether a ploidy or proliferation rate is a better predictor of tumor behavior than histological features. Nine of 10 neoplasms had both diploid and aneuploid modal populations. One neoplasm and all three control cases had only a diploid peak. Among the tumors, the DNA indices of the aneuploid peaks ranged from 1.1 to 2.2. The percentage of aneuploid cells ranged from 7 to 99, and no distinction was made between benign and malignant. Proliferation rates were estimated from the combined S-phase fractions (SPF). The mean SPF of the control group was 0.7% +/- 0.15% SD. The mean SPF of the benign tumors (1.1 +/- 0.82% SD) was significantly different from the malignant group (7.0 +/- 1.25% SD; range, 5.3 to 8.6%) P = 0.0095. Low SPF fractions always correlated with favorable outcome. Higher proliferation rates were generally associated with an aggressive course. Evaluation of proliferation rates may help predict the behavior of choroid plexus tumors, particularly when histological features are equivocal. Measurement of DNA ploidy does not appear to have a role in the evaluation of choroid plexus tumors.     

Cell proliferation activity and kinetic profile in the prognosis and therapeutic management of carcinoma of the pharynx and larynx.

Prognosis and management of carcinoma of the pharynx and larynx is now based on the morphologic analysis of the tumor spreading, differentiation grading, and type of microscopic invasion. The DNA ploidy status and the cell proliferation activity analyzed by flow cytometry give us complementary information about the prognosis and the management and support of the patients. We performed a study of 91 cases of carcinoma of the larynx and pharynx by means of flow cytometry. Forty-three patients were treated by surgery alone, and 48 patients also received radiotherapy. Fifty-five were aneuploid (60%); this percentage increased to 74% in the pharynx area and fell to 47% at the larynx level. The aneuploid tumors showed worse behavior in the patients treated by surgery alone compared with those who also received radiotherapy. The S-phase fraction was high in aneuploid tumors, in positive lymph nodes, and in advanced stages. The S-phase fraction was higher in poorly differentiated tumors. In patients treated by surgery alone, we noticed that by combining both cytometric variables two different kinetic profiles could be defined related to the patients' behavior. The diploid tumors with a low S phase had the greatest rates of survival, whereas diploid tumors with a high rate of S phase and aneuploids had a lower rate.