p53 gene mutation in human borderline epithelial ovarian tumors.
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Carcinoma↗
Biomedical subjects
D A Bell
Publications and source records attributed to D A Bell.
Early de novo ovarian carcinoma. A study of fourteen cases.
BACKGROUND: The search for methods of early detection of ovarian carcinoma in recent years has emphasized the lack of information regarding the histologic features of early carcinoma or its precursor lesions; few examples of early de novo ovarian carcinoma have been reported. METHODS: The clinicopathologic features of 14 cases of early ovarian carcinoma detected as microscopic findings in grossly normal ovaries retrieved from a consultation practice and the files of the Massachusetts General Hospital were reviewed. RESULTS: The patients ranged in age from 27-65 years (mean, 50 years). Three women had a family history of ovarian carcinoma and six did not. The tumors ranged from microscopic to 7 mm in greatest dimension; all were unilateral and four were multifocal. One tumor involved the surface and its crypts; four, the surface and superficial cortex; eight, the superficial cortex only; and in one, surface involvement was not ascertainable. Ten carcinomas were serous; one, endometrioid; one, clear cell; and two, poorly differentiated, of undetermined cell type. Severe atypia of the noncarcinomatous surface epithelium or its inclusion cysts was additionally present in three cases. Among the seven patients whose diagnoses were made at the time of oophorectomy who had follow-up data of at least 2 years or until recurrence or death, five were alive without recurrences, one was alive with recurrence, and one died of tumor. Two of the three women died whose ovarian tumors were diagnosed retrospectively on discovery of subsequent peritoneal carcinomatosis, and the third was alive with recurrent tumor. No relation between any clinical or pathologic feature and survival was apparent in this small series except for a suggestion that well differentiated tumors had a good prognosis. CONCLUSIONS: These findings document that at least a subset of ovarian epithelial cancers develops de novo. The guarded prognosis associated with these tumors despite their minute dimensions raises questions about the value of current screening techniques for early detection of ovarian cancer.
Adult↗
Dioxin-responsive genes: examination of dose-response relationships using quantitative reverse transcriptase-polymerase chain reaction.
The purpose of the present experiments was to examine dose-response relationships for induction of hepatic mRNA following a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to rats. The induction of cytochrome P450-1A1 (CYP1A1) mRNA is compared to other "dioxin-responsive" genes including UDP-glucuronosyltransferase I, plasminogen activator inhibitor 2, and transforming growth factor alpha using a sensitive reverse transcriptase-polymerase chain reaction-based method. Sample-to-sample variability in amplification is a concern in using polymerase chain reaction to quantitate biological responses. However, in the present study recombinant RNA templates were synthesized to use as internal standards in both the reverse transcription and the polymerase chain reaction steps. The induction of CYP1A1 mRNA was extremely sensitive to TCDD treatment with increases observed at doses as low as 1 ng/kg body weight. The induction of CYP1A1 mRNA correlated highly (R2 > 0.90) with an increase in ethoxyresorufin-o-deethylase activity, a CYP1A1-associated enzyme activity. However, induction of CYP1A1 mRNA levels was detected at lower TCDD doses than was ethoxyresorufin-o-deethylase activity, reflecting the greater sensitivity of the reverse transcription-polymerase chain reaction approach to detect transcriptional activation of the CYP1A1 gene. UDP-glucuronosyltransferase I mRNA was increased over control (5-fold) but required 1000-times higher TCDD doses (1 microgram/kg) to result in a significant increase than did CYP1A1. Plasminogen activator inhibitor 2 and transforming growth factor alpha mRNA, both previously shown to be induced by TCDD in human keratinocytes, were not increased in rat liver. Hence, these studies reaffirm that TCDD acts through classical receptor mechanisms with gene-to-gene differences in responsiveness. The reverse transcription-polymerase chain reaction method developed to measure mRNA for dioxin-responsive genes in rat liver will allow for measuring multigene and tissue responses to TCDD and other xenobiotics with high sensitivity, reproducibility, and adaptability and should increase our understanding of various dose-response relationships.
Animals↗
Mutation spectra in Salmonella of complex mixtures: comparison of urban air to benzo[a]pyrene.
We used an ion-exchange procedure coupled to the Salmonella assay to fractionate the dichloromethane-extractable particulate organics from an urban air sample collected in Boise, Idaho. A resulting base/neutral fraction contained 81% of the mutagenic activity but only 36% of the mass of the unfractionated sample. Chemical analysis showed that polycyclic aromatic hydrocarbons (PAHs) accounted for much of the mutagenic activity of the air sample. Colony probe hybridization, PCR, and DNA sequence analysis were then used to determine the mutations induced by the complex mixtures and a model PAH, benzo[a]pyrene (BAP) in approximately 900 revertants of the frameshift hisD3052 allele and approximately 400 revertants of the base-substitution hisG46 allele. The majority (93-94%) of the mutations induced at the frameshift allele in strain TA98 by the whole or base/neutral fraction of the urban air sample was a hotspot 2-base deletion of a CG or GC within the sequence CGCGCGCG. The remaining mutations were complex frameshifts that consisted of -2 or +1 frameshifts associated with a flanking base substitution. BAP induced a somewhat similar pattern of mutations, with 70% being the hotspot mutation, 23% being complex frameshifts, and the remaining being deletions. The inferred base-substitution specificity associated with the complex frameshifts at the hisD3052 allele (primarily G.C-->T.A transversions) was consistent with the observation that this same transversion was the primary mutation induced by the whole urban air sample and BAP at the base-substitution allele in strain TA100. At the frameshift allele, adducts that promote correct incorporation/slippage could account for hotspot mutations, whereas those that promote misincorporation/slippage could account for complex frameshifts. At the base-substitution allele, a mixture of adducts or of adducts with multiple conformations could account for the observed proportion of transitions and transversions. Combined with the bioassay-directed chemical analysis, these results from the first mutation spectra of a complex mixture suggest that such spectra reflect the dominance of particular classes of chemical mutagens within the mixture.
Air Pollutants↗
Prognostic significance of DNA content in epithelial ovarian cancer.
The prognostic significance of cellular DNA content of epithelial ovarian cancer as determined by flow-cytometric analysis of paraffin-embedded tumor blocks was investigated in 87 patients. Seventy-five percent of tumors were DNA aneuploid and 25% were DNA diploid. The survival at median follow-up for patients with DNA diploid tumors (68%) was significantly longer than for DNA aneuploid tumors (49%; P = 0.003). The other prognostic factors which significantly affected survival were stage (P < 0.0001), tumor grade (P < 0.006), and residual disease at completion of initial surgery (P = 0.0005). When patients were separated into low-stage and advanced-stage disease, DNA content was a significant prognostic variable for survival in Stage I and II patients (P = 0.05). In Stage III and IV patients, DNA content had no independent prognostic significance. There were 33 patients who underwent second-look surgery. Seven of 15 patients (47%) with negative second-look surgery were DNA aneuploid, whereas 17 of 18 patients (94%) with positive second-look surgery were DNA aneuploid. Therefore, there was a much higher likelihood of positive second-look in the DNA aneuploid group (17/24) compared to the DNA diploid group (1/9) (P = 0.003). In addition for those patients with negative second-look surgery, none (0/8) of the DNA diploid tumors recurred; however, 3 of 7 (43%) of the DNA aneuploid tumors recurred and died. Cox proportional/hazards analysis showed that DNA content is an independent prognostic factor for survival in epithelial ovarian cancer. Aneuploid DNA content in ovarian tumors is also correlated with more aggressive biologic behavior, and therefore, a worse clinical course.
Adult↗
Immunoglobulin V region sequences of two human antiplatelet monoclonal autoantibodies derived from B cells of normal origin.
Autoimmune thrombocytopenia has been attributed to the presence of antiplatelet autoantibodies which mediate platelet destruction. The derivation of these autoantibodies is presently unknown. While normal B cells do not produce these autoantibodies in vivo, it has been demonstrated in vitro by somatic cell hybridization that the B lymphocytes of nonthrombocytopenic individuals have the potential to produce antiplatelet autoantibodies. Antigen specificities of these antibodies are similar to those seen in autoimmune thrombocytopenic purpura and the lupus anticoagulant syndrome. The immunoglobulin V region genes encoding two such human monoclonal antiplatelet antibodies, an anti-GP IIb (STO 171) and an anti-phospholipid antibody (STO 103) derived from tonsillar lymphocytes of a non-thrombocytopenic male, have now been sequenced. These antiplatelet antibodies were found to be encoded by unmutated germline VH and VK genes. The third complementarity determining region (CDR3) of the genes encoding both of these antibodies have unique D regions with evidence of N-nucleotide additions, and the light chain genes show VK-JK junctional diversity. STO 103 is encoded by the VH4 V71-2 germline gene and a truncated JH4 gene. The light chain gene showed closest homology with the VK4 Humk18 gene and JK2 gene. STO 171 showed closest homology with the VH4.18 germline gene and had a complete germline JH6 gene. The light chain of STO 171 is encoded by the VK3 Humkv325 germline gene, which is also used by some rheumatoid factors and cold agglutinins, and a JK4 gene. Although these antibodies were not derived from circulating B cells or found to be actively producing antibody at the time they were harvested, it is possible that naturally occurring antibody producing B cells, similar to those represented here, are recruited for the development of pathogenic autoantibodies in immune thrombocytopenia.
Amino Acid Sequence↗
p53 expression in ovarian borderline tumors and stage I carcinomas.
Seventy-nine ovarian serous and mucinous borderline tumors, 36 stage I carcinomas and 39 stage II-IV carcinomas were studied for p53 protein accumulation with monoclonal antibody PAb1801.p53 protein was expressed in 14% of borderline tumors, 36% of stage I carcinomas, and 64% of higher stage carcinomas. All immunopositive carcinomas accumulated p53 protein in the primary tumor, and 95% of them showed concordance in staining among different tissue blocks. A difference in frequency of p53 protein accumulation between stage I and higher stage serous carcinomas was not statistically significant. p53 positivity was associated with microinvasion, microcarcinoma and coexistent carcinoma in mucinous borderline tumors (P = .025). An association between p53 protein expression and poor tumor differentiation in Stage I carcinomas as statistically significant (P = .03). p53 positivity was observed in a poorly differentiated endometrioid carcinoma as well as in adjacent benign endometriotic tissue. These results suggest that p53 abnormalities may be early events in ovarian cancer, possibly contributing to malignant transformation of some borderline tumors, endometriosis and other carcinoma precursors.
Adenocarcinoma, Mucinous↗
Polycyclic aromatic hydrocarbon-DNA adducts in smokers and their relationship to micronutrient levels and the glutathione-S-transferase M1 genotype.
Sixty-three male cigarette smokers were entered into a cross-sectional study to determine whether inverse associations existed between polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels and intake/serum levels of vitamin A, vitamin C and vitamin E. Associations between PAH-DNA adducts and intakes of carotene, as well as serum levels of beta-carotene, were also determined. Fasting blood samples were collected for assays of PAH-DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, beta-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined. Analysis of PAH-DNA adducts by competitive enzyme-linked immunosorbent assay (ELISA) indicated that 70% of the subjects had detectable adducts, with a mean of 4.38 adducts/10(8) nucleotides (range 1.00-24.1/10(8)). Pearson's method was utilized to determine whether any associations existed between the various host variables and PAH-DNA adducts. Previously, no significant associations were found between PAH-DNA adducts and cigarettes smoked/day, pack-years, daily/life-time tar exposures or plasma cotinine levels (Santella et al., Carcinogenesis, 13, 2041-2045, 1992). PAH-DNA adducts were inversely associated with serum cholesterol-adjusted vitamin E levels (r = -0.25, P < or = 0.05) and with smoking-adjusted vitamin C serum levels (r = -0.22, P < or = 0.09). Stratification by GSTM1 genotype indicated that these associations were limited to subjects with the null genotype. The relationship between adducts and serum cholesterol-adjusted vitamin E was significant in those of the null genotype (r = -0.38, P < or = 0.04), but not in those with the gene present (r = -0.12, P = 0.5). Similarly, for smoking-adjusted vitamin C, the relationship with adducts was stronger in subjects with the null genotype (r = -0.35, P < or = 0.06) than in those with GSTM1 present (r = -0.05, P = 0.77). These results are consistent with findings of prior epidemiological studies identifying significant inverse associations between anti-oxidant micronutrient status or GSTM1 genotype and the incidence of lung cancer. Additional studies should be conducted to confirm a possible role for vitamin E in PAH-DNA adduct formation and to explore further the possible roles of vitamin A, beta-carotene and vitamin C in modulating adduct formation and lung cancer risk.
Adult↗
Ethnic variation in the CYP2E1 gene: polymorphism analysis of 695 African-Americans, European-Americans and Taiwanese.
Human cytochrome P4502E1 (CYP2E1) is inducible by ethanol and is involved in metabolism of many known carcinogens including N-nitrosodimethylamine, butadiene, benzene, and carbon tetrachloride. A 50-fold variability in CYP2E1 enzyme activity in humans has been observed but it is unknown whether the basis for this variation is genetic or environmental. Recently, two restriction fragment length polymorphisms (RFLPs) within the CYP2E1 gene have been suggested as genetic markers of risk for cancer. The first was a Rsa I polymorphism in the 5' regulatory region that appeared to alter transcriptional activation of the gene and the second was a Dra I polymorphism located approximately 7000 bp downstream in an intron. Rare alleles at each of these loci have been associated with a reduced risk for lung cancer in Japanese and Swedish populations. We have used a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotype frequency for each of these CYP2E1 RFLPs in 695 individuals of Taiwanese, African-American or European-American background. Genotype and allele frequencies for Taiwanese were significantly different from those of African-Americans and European-Americans at either Rsa I or Dra I sites (p < 0.0001). Allele frequencies for African-Americans and European-Americans were significantly different at the Rsa I site (p = 0.03). The rare alleles (c2 and C) occurred at frequencies of 0.28 and 0.24 in Taiwanese, 0.01 and 0.08 in African-Americans, and 0.04 and 0.11 in European-Americans. In addition, we describe three haplotypes common to all three population samples and a fourth haplotype that was only detected in the Taiwanese population sample. This fourth haplotype may have been caused by a recombination event between these markers.(ABSTRACT TRUNCATED AT 250 WORDS)
Asian People↗
Bithalamic hyperintensity on T2-weighted MR: vascular causes and evaluation with MR angiography.
PURPOSE: To determine whether MR angiography can be used to differentiate between the two vascular causes of bithalamic hyperintensity on T2-weighted MR images: "top of the basilar" artery occlusion and deep cerebral vein thrombosis. METHODS: A retrospective review identified six patients with bithalamic T2 hyperintensity of vascular causes. MR angiography was performed in four patients, MR angiography and conventional angiography in one patient, and conventional angiography in one patient. Data pertaining to clinical presentation and hospital course were collected. MR angiographic techniques were multislab overlapping three-dimensional time-of-flight, 2-D time-of-flight, and 2-D phase-contrast. RESULTS: Three cases of top of the basilar artery occlusion and three cases of deep cerebral vein thrombosis were recognized. In all cases, T2 hyperintensity in a vascular distribution suggested cerebral occlusive disease. Infarction involving the thalami and basal ganglia was present in two cases of deep cerebral vein thrombosis. Infarction of the thalami, mesodiencephalic region, and cerebellar hemispheres was present in two cases of basilar artery occlusion. Bithalamic infarction alone was seen in one case of deep cerebral vein thrombosis and one case of basilar artery occlusion. In the five cases in which MR angiography was used, this technique accurately distinguished the vessels involved (arterial or venous). CONCLUSION: MR angiography is a useful adjunct to MR imaging in the evaluation of bithalamic T2 hyperintensity. It does help distinguish between the two vascular causes: top of basilar artery occlusion and deep cerebral vein thrombosis.
Adult↗
The emerging role of magnetic resonance imaging in rheumatology.
The role of magnetic resonance imaging (MRI) in imaging the central nervous system and in orthopedic radiology is now well accepted. Numerous applications of this technique also exist in the field of rheumatology, and it is anticipated that MRI will play an important part in the evaluation of treatments for the arthritides. In addition, MRI allows noninvasive investigation of other rheumatologic problems, such as avascular necrosis, tendon disorders and myopathy. This review outlines the current applications of MRI in rheumatologic practice.
Humans↗
L-myc proto-oncogene alleles and susceptibility to hepatocellular carcinoma.
A common inherited RFLP of the L-myc proto-oncogene has been reported to correlate with cancer susceptibility or prognosis for some tumors. Using a PCR-based RFLP assay on DNA extracted from peripheral blood samples, we determined the L-myc EcoRI genotype of patients with HCC, patients with other liver tumors, and healthy controls. In this polymorphism there are 2 alleles, L and S, which define 3 possible genotypes: LL, LS, and SS. While the genotype distribution of patients with other liver tumors and healthy controls do not differ from one another, both differ significantly from the genotype distribution of patients with HCC. This difference is primarily the result of a low frequency of the SS genotype among HCC patients compared to controls or other liver tumor patients. Persons with the SS genotype appear to be protected against HCC and have roughly one-ninth the risk of persons who carry one or more copies of the L allele. Within HCC cases, patients with different L-myc genotypes show slight, but not statistically significant, differences in tumor characteristics and survival.
Alleles↗
Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer.
BACKGROUND: Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. PURPOSE: We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. METHODS: Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. RESULTS: Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P < .001). CONCLUSIONS: These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype.
Base Sequence↗
p53 gene mutations and protein accumulation in human ovarian cancer.
Mutations of the p53 gene on chromosome 17p are a common genetic change in the malignant progression of many cancers. We have analyzed 38 malignant tumors of ovarian or peritoneal müllerian type for evidence of p53 variations at either the DNA or protein levels. Genetic studies were based on single-strand conformation polymorphism analysis and DNA sequencing of exons 2 through 11 of the p53 gene; mutations were detected in 79% of the tumors. These data show a statistically significant association between mutations at C.G pairs and a history of estrogen therapy. Two of 20 patients whose normal tissue could be studied carried germ-line mutations of p53. Immunohistochemical analysis of the p53 protein was carried out using monoclonal antibody PAb1801. Ninety-six percent of the missense mutations were associated with abnormal accumulation of p53 protein, but nonsense mutations, a splicing mutation, and most deletions did not result in p53 protein accumulation. A statistically significant association between p53 protein accumulation in poorly differentiated stage III serous carcinomas and small primary tumor size at diagnosis was found, perhaps suggesting that p53 protein accumulation accelerates the metastatic spread from a primary tumor. Overall, our findings indicate that alterations of p53 play a major role in ovarian cancer, including predisposition to the disease in some patients, and suggest a possible mechanism for somatic mutations leading to this cancer.
Amino Acid Sequence↗
Mutation of K-ras protooncogene in human ovarian epithelial tumors of borderline malignancy.
The mutation of K-ras protooncogene was examined in 44 cases of borderline ovarian epithelial tumors and 18 cases of invasive ovarian carcinomas. In borderline tumors, K-ras mutations are a common feature, having been found in 21 of 44 cases (48%). Twenty of the 21 mutations were identified at codon 12, and one was identified at codon 13. A detailed analysis of the mutation pattern of K-ras revealed a close association with the histological cell types of the tumor. Mutation of K-ras was detected at a higher frequency in mucinous borderline tumor (identified in 12 of 19 cases) compared to serous borderline tumor (identified in 9 of 25 cases). K-ras mutation was also detected in invasive mucinous and serous ovarian carcinomas, hence supporting the notion that borderline ovarian tumors may represent a pathological continuum between benign and frankly invasive diseases.
Adenocarcinoma, Mucinous↗
Human papillomavirus typing in patients with Papanicolaou smears showing squamous atypia.
Three hundred sixty consecutive patients followed at the Massachusetts General Hospital Colposcopy Clinic had HPV typing performed from exfoliated cervical cells by a commercially available dot blot hybridization assay. This assay tests for three groups of HPV types: 6/11, 16/18, and 31/33/35. Of this group, 171 patients were referred because of a Papanicolaou (Pap) smear showing squamous atypia. Of the 171 patients referred for squamous atypia, 17 (10%) had histologic evidence of CIN. Thirty-three of the 171 (19%) had detectable HPV DNA, and 28 of the 33 had high-risk HPV types (16/18, 31/33/35). Of the 17 women with CIN, only 6 (35%) had high-risk types and 11 (65%) had no HPV DNA detected. Of the 28 women with atypia and high-risk HPV types, only 6 (21%) had CIN. This study demonstrates that commercially available HPV typing when used in patients with Pap smears showing squamous atypia is not clinically useful in identifying patients for colposcopic referral.
Carcinoma in Situ↗
Epithelial ovarian tumors of borderline malignancy: long-term follow-up.
Thirty-nine patients underwent primary surgery for epithelial ovarian tumors of low malignant potential at the Massachusetts General Hospital between 1970 and 1980. Eighty-five percent of patients were found to have Stage I disease and 15% were found to have Stage III disease. Fifty-four percent of patients had a tumor with serous histology, 39% had a tumor with mucinous histology, and the remainder of patients had tumors with an endometrioid or mixed-cell type. Second malignancies and benign ovarian tumors were frequently found concomitantly with the borderline tumors or in follow-up. Gastrointestinal and endometrial adenocarcinomas were the most common second malignancies and were frequently found associated with a borderline tumor of serous histology. Follow-up was available in all 39 patients (100%). Mean time of follow-up was 11.8 years. Sixty-nine percent of patients are clinically without evidence of disease with a mean follow-up of 14.7 years, 23% died of other causes, 5% died of disease, and 3% died with disease and sepsis. All patients dying with disease did so within 7.3 years of their primary surgery. Seven patients underwent conservative surgery, defined as preservation of some ovarian tissue. Six of 7 patients are clinically free of disease with a mean follow-up of 14.6 years; 1 patient died of other causes. No patients treated conservatively had a recurrence of their disease.
Adenocarcinoma↗
DNA ploidy status: its impact on early-stage endometrial adenocarcinoma.
DNA ploidy status, as determined by flow cytometry, has been useful in predicting survival in certain malignancies. Between January 1975 and January 1985, 85 cases that met the inclusion criteria-pathologic stage I endometrial adenocarcinomas, primary surgical therapy, endometrioid cell type, and adequate paraffin-block samples-were analyzed by DNA flow cytometry. Depth of myometrial invasion, tumor grade, and presence of lymphatic vascular space invasion were established in all cases. Ten of the 85 tumors (12%) were aneuploid. The median follow-up was 9 years with a range of 2 to 16 years. There were 9 recurrences with 5 deaths from cancer, and 8 patients died of intercurrent disease. The relative hazards for recurrence associated with aneuploidy, S-phase fraction, grade 3 histology, and any myometrial invasion were 3.1, 3.18, 3.2, and 4.9, respectively, but did not reach statistical significance. Because of the low recurrence and mortality rate in this homogeneous group, a larger sample will be necessary to fully establish a role for DNA ploidy status in identifying a poor prognostic subset.
Adenocarcinoma↗