Substrate specificity of recombinant osteoclast-specific cathepsin K from rabbits

We studied image cytometric DNA analysis of bladder tumors to evaluate malignant potentials of bladder tumors. METHODS: Thirty nine samples were obtained by TUR from 37 patients. Nuclear DNA content of all samples were measured by image cytometer and were determined ploidy pattern by DNA histogram. RESULTS: Of 39 TCC non-diploid pattern was recognized in 50% of grade 1 cases, 73% of grade 2 cases and 100% of grade 3 cases. DNA ploidy was strictly correlated with histological grading in TCC. DNA non-diploid pattern was present in 67% of papillary tumors, 87.5% of non-papillary tumors and 100% in CIS. In diploid pattern 2 of 7 cases with grade 1 and 2 of 4 cases with grade 2 recurred. In non-diploid pattern 1 of 4 cases with grade 1, 4 of 10 cases with grade 2 and 4 of 6 cases with grade 3 recurred. There was no significant correlation between diploid and non-diploid pattern in grade 1, 2, 3. CONCLUSION: Image cytometric DNA analysis may be useful in addition to the classic and prognostic parameters of stage and grade, especially in TCC. The differences between image analysis system and flow cytometric analysis for DNA measurement were discussed.     

Measurements of energy expenditure using isotope-labelled water (2H2(18)O) during an Arctic expedition

An abnormal DNA content has been associated with an unfavorable prognosis in a variety of cancers. In this study, tumor DNA content was measured in patients with gallbladder carcinoma in order to determine whether DNA ploidy pattern was a prognostic indicator. Thirty-six patients who had had a gallbladder carcinoma resected with curative intent were analyzed. Aneuploid tumor (20 cases, 56 per cent) was significantly associated with poorly differentiated adenocarcinoma (p < 0.05), invasion beyond the muscularis propria (p < 0.01), and a high mitotic index (p < 0.0001). A significant advantage in terms of five-year survival was demonstrated in patients with diploid tumors as compared with those with aneuploid tumors (80 per cent versus 24 per cent, respectively, p < 0.005). Aneuploid tumors invading the subserosal layer had a significantly poorer prognosis than diploid tumors with similar depth of invasion (p < 0.05). However, when tumor invasion had extended beyond the serosa, no significant advantage in survival was found between patients with aneuploid and those with diploid tumors. It is concluded that DNA ploidy pattern is a valuable addition to a staging protocol for gallbladder carcinoma.     

C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk

The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.     

DNA ploidy, proliferative index and EGF-R status in 130 cases of resected gastric cancer--a multivariate analysis

BACKGROUND/AIMS: The purpose of this study was to define the prognostic role of DNA ploidy, proliferative index and EGF-R status in resected gastric cancer. MATERIALS AND METHODS: Ten clinico-pathological parameters and three biological factors obtained from flow cytometry and immunohisto-chemistry were evaluated in a series of 130 gastric cancer patients who received surgical treatment, including 28 stage IV cases (21.6%), using paraffin-embedded and fresh specimens in 77.7% and 22.3% of the cases, respectively. These variables were first analyzed and tested for correlation within the whole series and then weighted against survival in 117 applicable cases through univariate and multivariate analyses. RESULTS: Aneuploidy was significantly related to higher proliferative activity, EGF-R expression and deeper stomach wall infiltration. Higher proliferative activity was significantly related to deeper stomach wall infiltration and larger tumor diameter. The latter showed a significant relationship to EGF-R expression. Univariate analysis showed the significant variables for survival to be DNA ploidy, pT, pN, M, stage, histological type according to Lauren and tumor diameter. Multivariate analysis calculated on these significant variables using the Cox multiple stepwise regression model detected three factors which independently influence survival: pathological stage (p < 0.00001), histological type according to Lauren (p < 0.002) and DNA ploidy (p < 0.03). CONCLUSIONS: DNA ploidy was shown to be a significant prognostic parameter in resected gastric cancer after pathological stage and histological type according to Lauren. The prognostic roles of proliferative activity and EGF-R status require further investigation.     

S-phase fraction of 155 soft tissue sarcomas: correlation with clinical outcome

BACKGROUND: Traditionally, grade is considered the most important prognostic factor for soft tissue sarcomas (STS). However, because of the alleged difficulties in reproducibility of grading, new, objectively determined prognostic factors would be of value. The aim of our study was to establish if S-phase fraction (SPF) measured with flow cytometry was of prognostic significance for STS. METHODS: In this study, we included all 193 adult STS patients with superficial trunk or limb tumors who were treated by the Helsinki University Central Hospital (HUCH) STS group between January 1987 and May 1993. One hundred and seventy-two formalin fixed paraffin embedded tumor samples were available. SPF measurement was successful in 155 cases. RESULTS: Eighty-six cases were diploid. Ploidy was found to have no effect on overall survival. The median SPF was 6.8% (diploid tumors, 4% and nondiploid tumors, 12.9%). A high SPF predicted a shorter survival in patients with diploid tumors (P=0.003). The prognostic value was even stronger when we studied disease specific survival and excluded from analysis samples that contained less than 50% tumor cells (P=0.011). However, no prognostic value could be detected in nondiploid tumors or in the material as a whole. CONCLUSIONS: Our results suggest that high SPF is an adverse prognostic factor for survival of patients with diploid STS. However, further studies are needed to confirm these results.     

Evaluation of deoxyribonucleic acid ploidy and S-phase fraction as prognostic parameters in advanced epithelial ovarian carcinoma: a prospective study

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.     

A randomized double-blind trial of ondansetron alone versus in combination with dexamethasone versus in combination with dexamethasone and lorazepam in the prevention of emesis due to cisplatin-based chemotherapy

Sixty-five cases of invasive breast cancer < or = 1 cm. in largest diameter (pT1a-b) were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to proliferating cell nuclear antigen (PCNA). The percentage of PC10 positive tumor cells was closely related to histological grading. No association was found between PC10 score and nodal status. ER-ICA was performed on 42 cases and showed no correlation with PC10 staining. The clinical behaviour of these tumors was excellent, with 5-year survival rates overall of 96% (90% disease free survival), and apparently unrelated to histological type and grade, nodal involvement and hormonal receptor status. The prognostic value of PCNA labeling rates remains nuclear in breast cancer of minimal size as well as in larger ones.     

Increased urinary crosslink levels in aseptic loosening of total hip arthroplasty

BACKGROUND/AIM: The prognostic significance of DNA ploidy patterns of colorectal cancer has not yet been settled. The present study was designed to determine the prognostic value of DNA ploidy patterns for colorectal adenocarcinomas after curative resection. METHODS: DNA ploidy patterns of 140 colorectal adenocarcinomas were determined by DNA flow cytometry, and the prognostic significance of DNA ploidy patterns was evaluated by univariate as well as multivariate analysis. RESULTS: DNA ploidy patterns were diploid in 75 (53.6%) and aneuploid in 65 patients (46.4%). DNA ploidy patterns did not correlate with any of conventional prognostic variables. Univariate analysis disclosed that Dukes B2, C1, and C2 stages of the disease (p < 0.01), positive nodal metastases (p < 0.01), invasion through the intestinal wall (p < 0.01), and poor tumor differentiation (p < 0.05) were associated with worsened survival, but no correlation was found between DNA patterns and survival of patients. Multivariate analysis disclosed that tumor penetration through the bowel wall was associated with poorer survival of patients but the DNA ploidy pattern had no prognostic significance. CONCLUSIONS: A significant prognostic variable for patients after curative resection of colorectal adenocarcinoma was penetration of tumor through the bowel wall but not DNA ploidy patterns.     

Expression of p53 protein has no independent prognostic value in breast cancer

A series of 392 female breast carcinomas was analysed immunohistochemically for expression of p53 protein with special emphasis on the role of p53 as an independent prognostic factor. Altogether, 54.8 per cent of the carcinomas expressed p53 protein, with the mean [standard error (SE)] fraction of positive nuclei being 17.1 per cent (1.2 per cent). Expression of p53 protein was independent of tumour metastasis at diagnosis, axillary lymph node status, tumour diameter, histological type, tubule formation, proportion of intraductal growth, margin formation, necrosis, DNA ploidy, and S-phase fraction. A high fraction of p53-positive nuclei was significantly related to patient age under 70 years, high grade, severe nuclear pleomorphism, dense infiltration of tumour by lymphocytes, high mitotic index, and high apoptotic index (for all, P < 0.05). Impaired survival probability in the entire cohort (P = 0.05) and in the axillary lymph node-positive (ANP) tumours (P = 0.015) was associated with a fraction of p53-positive nuclei less than 25 per cent, while in the axillary lymph node-negative (ANN) tumours, expression of p53 had no prognostic value. In multivariate analysis, independent prognostic predictors included axillary lymph node status, tumour diameter, and mitotic index. In the ANN tumours, tumour diameter, fraction of p53-positive nuclei, and tumour grade were independent prognostic factors, whereas in the ANP tumours, diameter and mitotic index were the two independent prognostic factors. The results suggest that abnormal expression of p53 protein is only a weak independent prognostic factor in female breast cancer.     

Prognostic value of bcl-2 oncoprotein expression in stage II colon carcinoma

The bcl-2 proto-oncogene encodes a Mr 25,000 protein that has been shown to prevent apoptosis or programmed cell death. The bcl-2 protein is detectable in basal cells of normal colonic epithelium, and an altered topographic distribution of this protein is found in colonic neoplasms. However, the clinical significance of abnormal bcl-2 expression in colon carcinomas remains unknown. We examined the prognostic value of the bcl-2 protein in TNM stage II colon carcinomas and its relationship to DNA ploidy, cell proliferation indices, p53 expression, and clinicopathological features. We analyzed 119 resected and otherwise untreated, paraffin-embedded stage II colon carcinomas for bcl-2 and p53 protein expression using immunohistochemistry. DNA ploidy and proliferative index (% S-phase + % G2-M) were determined by flow cytometry, and tumor grade and vascular microinvasion were assessed on histological sections. Cytoplasmic expression of the bcl-2 protein was detected in 72 (66%) of 110 carcinomas, and a high level of expression was significantly correlated with diploid DNA content (P = 0.02) and low proliferative activity (P = 0.005). bcl-2 was not associated with nuclear p53 expression. In a univariate analysis, a higher fraction of bcl-2-positive tumor cells was associated with better relapse-free survival (P = 0.02) and overall survival (P = 0.05) rates. Moreover, a high level of bcl-2 expression was an independent predictor of better relapse-free survival (P = 0.04), but not overall survival (P = 0.14), after adjustment for other variables, including proliferative index, DNA ploidy, and race. In conclusion, bcl-2 overexpression is associated with favorable prognostic features and may predict clinical outcome in stage II colon carcinomas.     

Prognostic significance of the DNA index in a colorectal cancer

DNA flow cytometry was performed on paraffin-embedded tissue blocks made from 230 surgically resected colorectal cancers, 109 (47.4%) of which were diploid tumors, and 121 (52.6%) aneuploid tumors. The DNA index (DI) was calculated as the ratio of the G0/G1 channel number of tumor cells to the G0/G1 channel number of stromal cells. There was no significant difference in survival between patients with diploid tumors and those with aneuploid tumors (P = 0.322), although the survival rate was significantly lower in patients with a high DI (> or = 1.5) than in those with a low DI (< 1.5) (P = 0.004). A multivariate analysis of prognostic factors using Cox's proportional hazard model showed that Dukes' staging was the strongest predictor of survival, followed by the DI of tumor cells, then histological differentiation. In conclusion, it is suggested that the DI of tumor cells is instructive for predicting the survival of patients with colorectal cancer.     

Role of peptide-leukotrienes in bronchial asthma]

In the present study the prognostic value of both DNA ploidy and the proliferative activity of tumour cells were studied in a series of 76 consecutive patients suffering from gastric tumours. DNA ploidy and the proliferative index (as measured by the percentage of S-phase cells) were determined by flow cytometry using fresh tumour specimens. The presence of DNA aneuploid clones by flow cytometry was detected in 62% of the cases (mean DNA index of 1.63 +/- 0.46; range 1.08-2.92), the mean proportion of S-phase cells being of 18.4 +/- 11.5%. In comparison with diploid cases, aneuploid tumours showed a higher proliferative activity (cases with more than 15% S-phase cells: 18.4% versus 6.1%, p = 0.0001) as well as a higher incidence of node involvement (95% versus 68%, p = 0.001). By contrast, no significant differences were detected with respect to sex, age, histologic grade and type, clinical stage, tumour size and the incidence of extranodal involvement. Upon grouping the patients according to the proportion of S-phase cells no significant differences were observed for the clinical and biological parameters explored except for an association between a high percentage of S-phase cells and the presence of DNA aneuploidy (40% versus 96%, p = 0.0001). Regarding survival the presence of DNA aneuploidy was significantly associated with poor outcome as compared to the diploid cases (median of 15 versus 26 months, p = 0.005). By contrast, the proportion of S-phase cells did not predict patients's outcome. Multivariate analysis of prognostic factors showed that the presence of DNA aneuploidy (p = 0.003) together with the histologic type (p = 0.03) and the existence of extranodal metastases (p = 0.05) were the best combination of prognostic factors for survival prediction.     

The influence of blood volume changes on leucocyte and lymphocyte subpopulations in elite swimmers following interval training of varying intensities

BACKGROUND: Current staging systems for unresectable or metastatic neuroblastoma do not reliably predict responses to chemotherapy in infants under 1 year of age. Previous studies have indicated that the DNA content, or ploidy, of malignant neuroblasts can discriminate between good and poor responders in this group of patients, but the clinical utility of ploidy assessment has remained in question. PURPOSE: We tested, in a prospective nonrandomized study, the hypothesis that neuroblast ploidy could be used as the sole guide for treatment selection in infants with unresectable or metastatic tumors and could differentiate between those who would respond to our previous standard regimen and those who would benefit from an immediate switch to another therapy. METHODS: One hundred seventy-seven infants were enrolled in this trial. Five of these infants were subsequently excluded (two ineligible, two lacking ploidy information, and one protocol violation); therefore, 172 patients were included in the study. One hundred thirty infants with hyperdiploid tumors (DNA index > 1.0; better prognosis in retrospective studies) were treated with a well-tolerated regimen of cyclophosphamide (150 mg/m2 per day orally or intravenously on days 1-7) and doxorubicin (35 mg/m2 intravenously on day 8). Forty-two infants with diploid tumors (DNA index = 1.0; worse prognosis in retrospective studies) received cisplatin (90 mg/m2 intravenously on day 1) and teniposide (100 mg/ m2 intravenously on day 3) after an initial course of cyclophosphamide plus doxorubicin. Statistical end points were response and long-term survival. In addition, we assessed within each ploidy group (i.e., patients with hyperdiploid tumors and those with diploid tumors) the prognostic significance of NMYC gene copy number, tumor stage, and other variables commonly measured in this disease. RESULTS: Of the 127 assessable infants with hyperdiploid tumors, 115 (91%) had complete responses--85 after receiving five courses of cyclophosphamide plus doxorubicin and 30 after receiving further therapy including cisplatin plus teniposide. The 3-year survival estimate for the entire hyperdiploid group was 94% (95% confidence interval [CI] = 89%-98%). Nineteen (46%) of 41 assessable infants with diploid tumors were complete responders. The overall 3-year survival estimate for this group was 55% (95% CI = 39%-70%). Prognostic factor analysis indicated that NMYC gene amplification and an elevated serum lactate dehydrogenase level were statistically significant markers of higher risk disease within the diploid group (two-sided P values of .005 and .003, respectively). Only NMYC was predictive in the hyperdiploid group (P = .003). CONCLUSION: Use of a prognostic staging system based on tumor cell ploidy, augmented with the NMYC gene copy number and serum level of lactate dehydrogenase, would very likely improve the treatment of infants with unresectable or metastatic neuroblastoma. Patients with diploid tumors characterized by an amplified NMYC locus represent a particularly unfavorable risk group that may benefit from innovative new therapies.     

Effort and achievement in national family planning programmes

Cell proliferation of 174 specimens obtained from the primary gastric cancers using endoscopic biopsy was investigated by immunohistochemical analysis with the monoclonal antibody PC10, which recognizes a proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded material. All the examined samples showed nuclear staining for PCNA in cancer cells. The investigation was to test the correlation between PCNA labeling and lymph node metastasis. DNA aneuploidy was often encountered in tumors with nodal involvement and lymphatic invasion. The logistic regression analysis identified PCNA labeling rates (LRs), tumor size, and macroscopic type as independent significant factors for lymph node metastasis. When the PCNA LRs and clinicopathologic parameters were entered into the Cox regression analysis, PCNA LRs and DNA ploidy emerged as independent significant prognostic factors. In addition, combination assay of PCNA LRs and DNA ploidy yielded a powerful prognostic indication for patients with gastric cancer.     

The role of parathyroid hormone in the pathogenesis, prevention and treatment of postmenopausal osteoporosis

BACKGROUND: Nuclear deoxyribonucleic acid (DNA) content is a prognostic factor in several tumors, and decisions regarding treatment have been made using this parameter. Nevertheless, there is no agreement in head and neck cancer. The purpose of the present study was to ascertain whether tumor DNA content correlated with prognosis in cases of primary squamous cell carcinoma (SCC) of the oral cavity and tongue base. METHODS: A retrospective study of formalin-fixed, paraffin-embedded tissue from patients with histologically confirmed SCC of the oral cavity and tongue base was performed using flow cytometry. Tumor DNA content was studied in 109 sets of specimens from previously untreated patients. All of them underwent surgical resection at the University "Hospital de La Princesa" between 1982 and 1992. Clinical parameters (age, sex, site of primary tumor, clinical stage, adjuvant therapy received, and disease-free and overall survival) and histologic parameters (histopathologic stage, tumor differentiation, type of inflammatory infiltration, presence of perineural invasion) were recorded in all cases. An exhaustive statistical analysis was applied. RESULTS: Only the histograms of 93 patients were adequate for consideration. In flow cytometric analysis, DNA aneuploidy was observed in 51 tumors (55%). The proportion of aneuploid tumors was significantly higher in advanced-stage carcinomas (p < .05), tumors with perineural invasion (p < .05) and in men (p < .05). In the 24 patients with lymph node metastasis, the incidence of aneuploidy was 82% (19 of 24) (p < .05). The rate of metastasis and aneuploidy increased as the degree of differentiation decreased (p < .05 for both). Patients with aneuploid carcinomas in both early and advanced stages had shorter relapse-free and overall survival periods than did the patients with diploid tumors (p < .001 for both). A Cox regression analysis demonstrated that ploidy was the single most important prognostic factor in determining relapse and death (p < .001 for both). CONCLUSIONS: The results indicate that tumor DNA analysis by flow cytometry appears to be useful as a supplement to clinical and histologic evaluation in predicting the tendency of SCC of the oral cavity and tongue base to metastasize to regional lymph nodes and to predict the outcome of the disease.     

Prognostic parameters of renal cell carcinoma. Clinicopathologic and DNA image cytometric analysis in 133 pT3a cases

In 133 cases of patients with renal cell carcinoma which infiltrated locally into the renal fatty tissue (stage pT3a, TNM classification of 1987), the prognostic potential of the following parameters was investigated: symptoms, patient's age at the time of operation, tumor size and localization, grade of malignancy, cell type, growth pattern, and prognostic score according to St?rkel et al. [Eur Urol 1990;18(suppl 2):36]. Additionally, automated image analysis DNA cytometry was performed on 110/133 carcinomas. After an average observation period of 3.6 years (maximum 10.1 years), 59 (44.4%) of the patients died of their tumors. The cause-specific 5- and 10-year survival rates were 51.3 and 29.1%, respectively. Statistically significant differences (p < 0.05) within the individual parameters were found only for the grade of malignancy and the corresponding prognostic score. Using DNA cytometry, 13 types of renal cell carcinoma were differentiated; 90% of the tumors contained aneuploid cells. Significant differences between these relative to prognosis did not exist. In the case of locally advanced renal cell carcinoma, the DNA histogram does not seem to be superior to conventional prognostic criteria.     

Disseminated intravascular coagulation: pathophysiology and principles of management

OBJECTIVE: To analyze the survival and the main prognostic factors in patients with transitional cell carcinoma of the upper urinary tract. METHODS: From 1983 to 1996, we treated 50 patients with transitional cell carcinoma of the upper urinary tract. Treatment was basically conservative except in those cases whose tumor stage or grade required a radical approach. Grading and staging were performed according to the 1992 TNM classification. Eighteen patients had died at one year mean follow-up., At the time the study was completed (June, 1997), 32 patients were alive with a mean follow-up of 4.9 years. Disease-free survival, overall and specific survival were analyzed according to sex, age, association with bladder tumors, localization, type of treatment, tumor size, number, histological grade and stage. RESULTS: The male-to-female ratio was 5:1. Patient mean age was 65.7 years. Association with bladder tumors was observed in 50%. Treatment was conservative in 40% and radical in 60%. The five- and ten-year disease-free survival rates were 69%, overall survival 61% and specific survival 71%. The univariate analysis showed the following to be unfavorable prognostic factors for survival: renal vs ureteral tumors, radical vs conservative treatment, high grade and stage tumors. The association of carcinoma in situ with other tumors of the upper urinary tract was also found to be an unfavorable factor for disease-free survival. The multivariate analysis associated T4 and G3 tumors with poor prognosis. CONCLUSIONS: Transitional cell carcinoma of the upper urinary tract was associated with bladder tumors in 50% of the cases. Low grade stage tumors demonstrated a high survival rate, therefore conservative treatment should be the first approach. High grade/ stage tumors were found to be unfavorable prognostic factors for survival.     

Relationship between DNA ploidy level, nuclear size, and survival in large cell lymphoma

Intermediate and high grade subtypes of non-Hodgkin's large cell (LCL) and immunoblastic lymphomas exhibit considerable variability, and histologic morphology alone may not adequately characterize those features important for prognosis. The relationship between nuclear morphology and survival was assessed in a series of 50 cases of large cell lymphomas in which ploidy, proliferation, and nuclear area (NA) were measured. Ploidy was calculated by both DNA index (DI) and DNA histogram type (DHT). Proliferation was calculated from the proportion of S phase (SPF) cells present in the DHT. These four parameters were measured using image cytometry of Feulgen-stained nuclei from fine-needle aspirations. To characterize the relationship with survival, these parameters were associated with the clinical follow-up of the patients. The results show that of the 50 LCL cases, only 5 were clearly aneuploid, whereas the remaining 45 were either diploid (29 cases), tetraploid/hypotetraploid (13 cases), or weakly aneuploid (hyperdiploid, 3 cases). Of the 34 patients who died from their disease, both smaller NA and DI correlated with longer survival in an equivalent fashion; neither conferred greater sensitivity when combined with the other. The SPF did not correlate with survival. In LCL, aneuploidy seems to be a relatively uncommon event, but when present ploidy measurement appears useful to define prognosis.     

Early diagnostic indices for the prevention of Alzheimer''s disease

A flow-cytometric (FCM) and fluorescence in situ hybridization (FISH) study was performed in 153 patients with clinically localised prostate cancer (PC) to evaluate retrospectively the prognostic significance of DNA ploidy, S-phase fraction (SPF) and chromosome 7 copy number. Deletions in 7q31.1 were analysed in a subset of 26 tumours. The mean follow-up time was 6 years (range 4-16 years). Twelve cases of benign prostatic hyperplasia (BPH) were studied as a control. Chromosome 7 enumeration and deletion studies were conducted using the alpha-satellite D7Z1 probe and a cosmid probe specific for the marker D7S522 on 7q31.1. Higher SPF was associated with shorter overall survival and shorter time to local progression and metastasis. Near diploid (DNA index 1.05-1.20) cases had a lower frequency of metastases and lower Gleason scores than aneuploid cases. Increased absolute chromosome 7 copy number (centromere count) was associated with higher Gleason score, higher SPF and shorter local progression-free and prostate cancer survival. Absolute chromosome 7 copy number was concordant with FCM DNA ploidy in the majority (75%) of cases. Relative gain or loss of chromosome 7 (centromere counts compared to ploidy) was infrequent, and no correlation was found with clinical parameters. Deletions in 7q31.1 were infrequent. Our results indicate that in localised PC (i) SPF is a prognostic factor, (ii) absolute chromosome 7 copy number is concordant with the ploidy status of the tumour (relative gain or loss of chromosome 7 is infrequent and has no independent prognostic value) and (iii) the frequency of deletions in 7q31.1 is low and not correlated with clinical outcome.     

Analysis of DNA content in supraglottic epidermoid carcinoma

DNA analysis by flow cytometry is considered to be of prognostic value in epidermoid carcinoma of the head and neck. However, few and contradictory studies have been made on laryngeal carcinomas. We studied 48 epidermoid carcinomas in patients subjected to horizontal supraglottic laryngectomy with a 5-year- followup. The technique described by Hedley for fixated and paraffin-embedded tumors was used. Thirteen tumors were excluded on the grounds of presenting variation coefficients in excess of 10. Of the 35 cases analyzed, 28 (80%) were diploid and seven (20%) aneuploid. No correlation was observed between tumor ploidy and patient survival, recurrence, or any of the histopathological variables studied.