The role of family factors in the association between early adulthood BMI and risk of cardiovascular disease. An intergenerational study of BMI in early adulthood and cardiovascular mortality in parents, aunts and uncles.

BACKGROUND: High body mass index (BMI) in childhood and adolescence is related to cardiovascular disease (CVD). Causality is not established because common genetic or early life socioeconomic factors (family factors) may explain this relationship. We aimed to study the role of family factors in the association between BMI and CVD by investigating if early adulthood BMI in conscripts and CVD mortality in their parents/aunts/uncles are related. METHODS: Data from the Armed Forces Personnel Database (including height and weight among conscripts) were linked with data from the Norwegian Population Registry, generational data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry using unique personal identification numbers. The study sample (N = 369,464) was Norwegian males born 1967-1993, who could be linked to both parents and at least one maternal and one paternal aunt or uncle. Subsamples were identified as conscripts whose parents/aunts/uncles had data on cardiovascular risk factors available from Norwegian health surveys. Cox proportional hazards regression models were used to estimate hazard ratios (HR) of CVD mortality in the parental generation according to BMI categories of conscripts. RESULTS: Parents of conscripts with obesity or overweight had a higher hazard of CVD death (fathers HR obese: 1.99 (1.79, 2.21), overweight: 1.33 (1.24, 1.42) mothers HR obese: 1.65 (1.32, 2.07), overweight: 1.23 (1.07, 1.42)) than parents of normal- or underweight conscripts. Aunts and uncles of conscripts with obesity and overweight had an elevated hazard of CVD death, but less so than parents. Adjustment for CVD risk factors attenuated the results in parents, aunts and uncles. CONCLUSIONS: Family factors may impact the relationship between early adulthood overweight and CVD in parents. These can be genes with impact on BMI over generations and genes with a pleiotropic effect on both obesity and CVD, as well as shared environment over generations.

Diagnostic tests and treatment procedures performed prior to cardiovascular death in individuals with severe mental illness.

OBJECTIVE: To examine whether severe mental illnesses (i.e., schizophrenia or bipolar disorder) affected diagnostic testing and treatment for cardiovascular diseases in primary and specialized health care. METHODS: We performed a nationwide study of 72 385 individuals who died from cardiovascular disease, of whom 1487 had been diagnosed with severe mental illnesses. Log-binomial regression analysis was applied to study the impact of severe mental illnesses on the uptake of diagnostic tests (e.g., 24-h blood pressure, glucose/HbA1c measurements, electrocardiography, echocardiography, coronary angiography, and ultrasound of peripheral vessels) and invasive cardiovascular treatments (i.e., revascularization, arrhythmia treatment, and vascular surgery). RESULTS: Patients with and without severe mental illnesses had similar prevalences of cardiovascular diagnostic tests performed in primary care, but patients with schizophrenia had lower prevalences of specialized cardiovascular examinations (prevalence ratio (PR) 0.78; 95% CI 0.73-0.85). Subjects with severe mental illnesses had lower prevalences of invasive cardiovascular treatments (schizophrenia, PR 0.58; 95% CI 0.49-0.70, bipolar disorder, PR 0.78; 95% CI 0.66-0.92). The prevalence of invasive cardiovascular treatments was similar in patients with and without severe mental illnesses when cardiovascular disease was diagnosed before death. CONCLUSION: Better access to specialized cardiovascular examinations is important to ensure equal cardiovascular treatments among individuals with severe mental illnesses.

Undiagnosed cardiovascular disease prior to cardiovascular death in individuals with severe mental illness.

OBJECTIVE: To examine whether individuals with schizophrenia (SCZ) or bipolar disorder (BD) had equal likelihood of not being diagnosed with cardiovascular disease (CVD) prior to cardiovascular death, compared to individuals without SCZ or BD. METHODS: Multivariate logistic regression analysis including nationwide data of 72 451 cardiovascular deaths in the years 2011-2016. Of these, 814 had a SCZ diagnosis and 673 a BD diagnosis in primary or specialist health care. RESULTS: Individuals with SCZ were 66% more likely (OR: 1.66; 95% CI: 1.39-1.98), women with BD were 38% more likely (adjusted OR: 1.38; 95% CI: 1.04-1.82), and men with BD were equally likely (OR: 0.88, 95% CI: 0.63-1.24) not to be diagnosed with CVD prior to cardiovascular death, compared to individuals without SMI. Almost all (98%) individuals with SMI and undiagnosed CVD had visited primary or specialized somatic health care prior to death, compared to 88% among the other individuals who died of CVD. CONCLUSION: Individuals with SCZ and women with BD are more likely to die due to undiagnosed CVD, despite increased risk of CVD and many contacts with primary and specialized somatic care. Strengthened efforts to prevent, recognize, and treat CVD in individuals with SMI from young age are needed.

Offspring birth weight and cardiovascular mortality among parents: the role of cardiovascular risk factors.

An inverse association between offspring birth weight (BW) and higher risk of parental cardiovascular disease (CVD) mortality and morbidity has been reported. Shared environmental, genetic and intrauterine factors may be responsible for explaining these associations. We studied the role of parental CVD risk factors in the association between offspring BW and CVD mortality among mothers and fathers. All births registered in Medical Birth Registry Norway (1967-2012) were linked to three health surveys, National Educational Registry and Cause of Death Registry. Number of births with information of parental CVD risk factors available for the analyses was 1,006,557 (520,670 for mothers and 485,887 for fathers). Cox proportional hazards regression models were used, following CVD deaths in parents from 1974 to 2012. An inverse association between offspring BW and CVD mortality was observed among both parents: hazard ratio 1.60 (1.44-1.75) for mothers and 1.16 (1.10-1.23) for fathers. Among mothers, adjustment for smoking, triglycerides and diabetes reduced the risk to 1.36 (1.25-1.52), 1.57 (1.43-1.73) and 1.58 (1.43-1.79), respectively. Adjustment for diastolic blood pressure (DBP) and systolic blood pressure (SBP) both reduced the risk to 1.53 (1.37-1.66). Among fathers, adjustments for smoking, DBP, SBP reduced the risk to 1.08 (1.02-1.15), 1.13 (1.06-1.19) and 1.14 (1.08-1.22), respectively. Triglycerides and diabetes both reduced the risk to 1.15 (1.09-1.12). Our results indicate that shared environmental factors might be important in the association. A stronger association in mothers suggest that intrauterine factors also are at play.

The interplay between cognitive ability, alcohol consumption, and health characteristics.

BACKGROUND: Higher cognitive ability is associated with favourable health characteristics. The relation between ability and alcohol consumption, and their interplay with other health characteristics, is unclear. We aimed to assess the relationship between cognitive ability and alcohol consumption and to assess whether alcohol consumption relates differently to health characteristics across strata of ability. METHODS: For 63 120 Norwegian males, data on cognitive ability in early adulthood were linked to midlife data on alcohol consumption frequency (times per month, 0-30) and other health characteristics, including cardiovascular risk factors and mental distress. Relations were assessed using linear regression and reported as unstandardised beta coefficients [95% confidence interval (CI)]. RESULTS: The mean ± s.d. frequency of total alcohol consumption in the sample was 4.0 ± 3.8 times per month. In the low, medium, and high group of ability, the frequencies were 3.0 ± 3.3, 3.7 ± 3.5, and 4.7 ± 4.1, respectively. In the full sample, alcohol consumption was associated with physical activity, heart rate, fat mass, smoking, and mental distress. Most notably, each additional day of consumption was associated with a 0.54% (0.44-0.64) and 0.14% (0.09-0.18) increase in the probability of current smoking and mental distress, respectively. In each strata of ability (low, medium, high), estimates were 0.87% (0.57-1.17), 0.48% (0.31-0.66) and 0.49% (0.36-0.62) for current smoking, and 0.44% (0.28-0.60), 0.10% (0.02-0.18), and 0.09% (0.03-0.15) for mental distress, respectively. CONCLUSIONS: Participants with low cognitive ability drink less frequently, but in this group, more frequent alcohol consumption is more strongly associated with adverse health characteristics.

Hyperemesis gravidarum and long-term mortality: a population-based cohort study.

OBJECTIVE: To investigate whether exposure to hyperemesis gravidarum (HG) is associated with increased maternal long-term mortality. DESIGN: Population-based cohort study. SETTING: Medical Birth Registry of Norway (1967-2002) linked to the Cause of Death Registry. POPULATION: Women in Norway with singleton births in the period 1967-2002, with and without HG. Women were followed until 2009 or death. METHODS: Cox proportional hazard regression model was applied to estimate hazard ratios (HRs) with 95% confidence interval (CI). MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality during follow up. Secondary outcomes were cause-specific mortality (cardiovascular mortality, deaths due to cancer, external causes or mental and behavioural disorders). RESULTS: Of 999 161 women with singleton births, 13 397 (1.3%) experienced HG. During a median follow up of 26 years (25 902 036 person-years), 43 470 women died (4.4%). Women exposed to HG had a lower risk of long-term all-cause mortality compared with women without HG (crude HR 0.82; 95% CI 0.75-0.90). When adjusting for confounders, this reduction was no longer significant (adjusted HR 0.92; 95% CI 0.84-1.01). Women exposed to HG had a similar risk of cardiovascular death as women not exposed (adjusted HR 1.04; 95% CI 0.83-1.29), but a lower long-term risk of death from cancer (adjusted HR 0.86; 95% CI 0.75-0.98). CONCLUSION: In this large population-based cohort study, HG was not associated with an increased risk of long-term all-cause mortality. Women exposed to HG had no increase in mortality due to cardiovascular disease, but had a reduced risk of death from cancer. TWEETABLE ABSTRACT: Population-based cohort study: Hyperemesis was not associated with an increased risk of long-term mortality.

Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

AIMS: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). METHODS: Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. RESULTS: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). CONCLUSIONS: Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

The associations between maternal pre-pregnancy body mass index or gestational weight change during pregnancy and body mass index of the child at 3 years of age.

OBJECTIVE: To estimate the associations between maternal pre-pregnancy body mass index (BMI) or gestational weight change (GWC) during pregnancy and offspring BMI at 3 years of age, while taking several pre-and postnatal factors into account. DESIGN: The Norwegian Mother and Child Cohort Study is a population-based pregnancy cohort study of women recruited from all geographical areas of Norway. SUBJECTS: The study includes 31 169 women enrolled between 2000 and 2009 through a postal invitation sent to women at 17-18 weeks of gestation. Data collected from 5898 of the fathers were included. MAIN OUTCOME MESURES: Offspring BMI at 3 years was the main outcome measured in this study. RESULTS: Mean maternal pre-pregnancy BMI was 24.0 kg m(-2) (s.d. 4.1), mean GWC in the first 30 weeks of gestation was 9.0 kg (s.d. 4.1) and mean offspring BMI at 3 years of age was 16.1 kg m(-2) (s.d. 1.5). Both maternal pre-pregnancy BMI and GWC were positively associated with mean offspring BMI at 3 years of age. Pre-pregnancy BMI and GWC also interacted, and the strength of the interaction between these two factors was strongly associated with the increase in offspring BMI among mothers who gained the most weight during pregnancy and had the highest pre-pregnancy BMI. Our findings show that results could be biased by not including pre-pregnant paternal BMI. CONCLUSION(S): This large population-based study showed that both maternal pre-pregnancy BMI and GWC were positively associated with mean offspring BMI at 3 years of age.

Life course influence of residential area on cause-specific mortality.

OBJECTIVE: To examine the relative influence of area of residence on mortality risk along the life course in different age groups and to see if this differs for causes known to be related differently to various models of the life course. METHODS: Individual data from the Censuses in 1960, 1970, 1980 and 1990 from Oslo, Norway, were linked to the death register 1990-1998. All male inhabitants living in Oslo in 1990 aged 30-69 years who had lived in Oslo at the three previous Censuses were included. RESULTS: In the youngest age group, area of residence closest to the time of death is most important for violent and psychiatric causes. In older age groups, area of residence at all time points in the period studied seemed to have a similar influence. Cardiovascular deaths were related to earlier as well as later area of residence in both young and old age groups. For violent and psychiatric causes, the most recent area may be the most important. CONCLUSION: This paper explores a research strategy to investigate how the area of residence through the life course influences mortality. The associations seem to vary according to age at, and cause of, death.

Reduced expression of Claudin-7 in fine needle aspirates from breast carcinomas correlate with grading and metastatic disease.

OBJECTIVE: To study the immunocytochemical expression of the tight junction protein Claudin-7 in smears from breast carcinomas and correlate with grading, nodal status, locoregional and distant metastases and the cellular cohesion. METHODS: The material consisted of 52 air-dried smears from fine needle aspirates of breast carcinomas, both primary and metastatic and smears from seven benign lesions. A primary antibody to Claudin-7 was used for immunocytochemical staining. The degree of staining was recorded as negative, reduced or full, with full expression meaning equivalent to the staining pattern found in the fibroadenomas used as benign control. Staining intensity and the percentage of stained cells were evaluated. The control smears revealed a strong membrane and cytoplasmic positivity in all luminal epithelial cells. Cellular cohesion was graded as: (1) mainly cohesive groups, (2) groups and single cells and (3) mainly single cells. RESULTS: All primary and recurrent/metastatic breast lesions expressed Claudin-7. Full expression was demonstrated in 46% of the cases. Reduced expression was found in 54%. In cases with reduced expression, the percentage of stained cells were usually high, and no smear showed <50% stained tumour cells. The staining pattern was heterogeneous and always mixed membrane/cytoplasmic. Claudin-7 expression showed a significant correlation (P < 0.05) with grading, locoregional and distant metastases, nodal involvement and cellular cohesion in invasive carcinomas, but not with tumour size or subtype. CONCLUSION: Reduced expression of Claudin-7 correlated with higher tumour grade, metastatic disease, including loco-regional recurrences and with cellular discohesion.

Immunocytochemical expression of E-cadherin on fine-needle aspirates from breast carcinomas correlate with the cell dissociation pattern seen on smears.

Altered E-cadherin expression has been suggested to be of prognostic significance in breast cancers and to correlate with tumor subtype and grade. A dysfunctional, intercellular adhesion system may be responsible for the tumor cell dissociation pattern seen on fine-needle aspirate cytology (FNAC). The aim of our study was to determine E-cadherin expression on direct FNAC smears from breast carcinomas and compare the results with the dyscohesion grade of the tumor cells and the cytological grading. The material consisted of FNAs from 56 breast carcinomas. The degree of cellular cohesion was estimated semiquantitatively. Full expression of E-cadherin was defined as a complete and strong membrane staining of virtually all tumor cells. All nonductal as well as 85% of the invasive ductal carcinomas revealed reduced expression or negativity for E-cadherin. In all, 25% of carcinomas with dyscohesion Grade 1 (mainly in groups) revealed full expression of E-cadherin, in contrast to 12.5% of tumors with dyscohesion Grade 3 (mainly dispersed cells). Nuclear positivity was seen in 21% of the tumors (12 cases) and seven of these were G3 ductal carcinomas. In conclusion, E-cadherin expression correlated with the cell dissociation pattern seen on direct smears from FNAC of breast carcinomas, but is only one of several markers that modulate this pattern. High-grade carcinomas rarely revealed full expression and had a high incidence of aberrant nuclear localization of E-cadherin.

Microemulsion electrokinetic chromatography in suppressed electroosmotic flow environment. Separation of fat-soluble vitamins.

Microemulsion electrokinetic chromatography (MEEKC) was carried out in a pH 2.5 phosphate buffer to effectively suppress the electroosmotic flow (EOF). With 66.6% (w/w) 25 mM phosphate buffer pH 2.5, 20.0% (w/w) 2-propanol, 6.6% (w/w) 1-butanol, 6.0% (w/w) sodium lauryl sulphate (SDS), and 0.8% (w/w) n-octane as the separation medium, the fat-soluble vitamins A palmitate, E acetate, and D3 were baseline separated within 11 min. With strongly suppressed EOF, the polarity of the separation voltage was reversed (positive electrode at the outlet); the n-octane micro droplets surrounded by negatively charged SDS molecules migrated towards the detector. The aqueous part of the microemulsion was modified with 20% (w/w) 2-propanol to improve partition between the n-octane phase and the surrounding aqueous medium. The fat-soluble vitamins were separated in order of decreasing hydrophobicity with a high migration time stability (repeatable within 0.1% RSD). Excellent accuracy and precision were obtained when the system was applied for the determination of vitamin E acetate in commercial vitamin tablets; quantitative data corresponded to 97.0% of label claim, intra-day results varied within 1.72% RSD (n=6), and inter-day results varied within 3.22% RSD (n=5).

Estimating loss of the wild-type p53 gene by in situ hybridization of fine-needle aspirates from breast carcinomas.

TP53 mutations have been found in 16-64% of breast carcinomas. The aim of our study was to investigate loss of the wild-type TP53 gene by in situ hybridization (ISH) of fine-needle aspirates (FNAC) from breast carcinomas. The material consisted of FNAC from 33 breast carcinomas, with histologic specimens from 19 of the cases. Routine diagnostic smears were used for cytologic grading. ISH of the wild-type TP53 gene and chromosome 17 was performed on air-dried smears. Hybridization signals were counted in at least 100 nuclei, and the percentage for each signal number was calculated. FNAC from four fibroadenomas as well as cell preparations from five lymphocyte cultures were used as normal/benign controls. Cutoff for defining loss of p53 gene signals was set at 20% of cells with zero and one gene signal only. Concomitant p53 protein expression was determined on 20 histologic sections and eight additionally available air-dried smears. Loss of wild-type p53 gene was found in 20 carcinomas (60.6%). The rate of signal loss varied from 0.4% to 75.3% of the cells. All tumors with aneusomy of chromosome 17 revealed loss of p53 gene signals, as did 42% of the disome cases. Loss of wild-type p53 gene was present in 10 of 16 grade 1 cancers (62.5%), eight of 13 grade 2 tumors (61.5%), and two of four grade 3 cases. Signal loss did not correlate with p53 protein expression. In conclusion, subpopulations with loss of the wild-type p53 gene are a common finding in breast carcinomas; they are detected in more than 60% of the tumors, including grade 1 cancers.

Numerical abnormalities of chromosome 7 in interphase cell nuclei of breast carcinoma have no impact on immunohistochemically determined EGFR status.

AIM OF STUDY: To investigate the relationship between epidermal growth factor receptor (EGFR) status and numerical aberrations of chromosome 7 in breast carcinomas. DESIGN: In situ hybridization (ISH) of interphase cell nuclei on air-dried fine-needle aspirates (FNAC) from 33 breast carcinomas was evaluated for numerical abnormalities in chromosome 6, 7, 12 and 17. Immunohistochemical staining of EGFR was performed on corresponding histological specimens. RESULTS: 78% of the tumours were aneuploid by ISH. Aneusomy of chromosome 7 was found in 18 cases (60%). EGFR overexpression was observed in 30% of the carcinomas, and seven of nine were aneuploid by ISH. The same percentage of chromosome 7 aneusomy was found in both EGFR-positive and -negative cases. Five of seven EGFR-positive tumours revealed aneusomy of chromosome 7. CONCLUSION: Numerical gain of chromosome 7 is a common finding, occurring in about 60% of breast carcinomas. Most EGFR-positive tumours are aneuploid and show numerical gain of chromosome 7, but abnormal numbers of chromosome 7 have no impact on the EGFR status.

Analysis of vitamin formulations by electrokinetic chromatography utilizing tetradecylammonium ions as the pseudostationary phase.

A recently proposed method for the separation of fat-soluble vitamins by electrokinetic chromatography was further developed and investigated in the present study. The separation medium consisted of acetonitrile-water (80:20 v/v) and contained 80 mM tetradecylammonium bromide (TDA+); the content of acetonitrile served to maintain the hydrophobic vitamins dissolved during electrophoresis, while the TDA+ ions served as the pseudostationary phase. With the cathode placed at the outlet of the capillary, the fat-soluble vitamins were separated based on different hydrophobic interactions to the TDA+ ions and migrated in order of decreasing hydrophobicity prior to the electroosmotic flow. Migration time stability was significantly enhanced by the addition of 4 mM borate to the separation medium. The separation system was validated for the determination of vitamin E acetate in commercial tablets; quantitative results deviated by less than 3.5% from specified values, varying by less than 2.5% relative standard deviation (RSD) for within-day experiments, and by less than 6.5% RSD during between-day experiments. The separation system was compatible with injection solvents ranging in polarity from water to tetrahydrofuran, and was even capable of separating the water-soluble vitamins B1, B2, B12, and nicotinamide.

Numerical aberrations of chromosome 17 in interphase cell nuclei of breast carcinoma cells: lack of correlation with abnormal expression of p53, neu and nm23 protein.

The genes for p53, neu (c-erbB-2) and nm23 are all located on chromosome 17. Abnormal expression of their protein products is an important prognostic parameter. The aim of this study was to investigate if numerical aberrations of chromosome 17 are reflected in the expression of these markers. The immunohistochemical expression was analysed on histological specimens from 33 breast carcinomas. In situ hybridization (ISH) was performed on interphase cell nuclei in air-dried fine-needle aspirates from the same cases using a digoxigenin-labelled alpha-satellite probe for chromosome 17. ISH for chromosome 6, 7 and 12 was used additionally to give an estimate of ploidy. Of the carcinomas 76% were aneuploid, and numerical abnormalities of chromosome 17 were found in 34%. Abnormal p53 protein was expressed in 15% (five cases). All of these were aneuploid, but only one of them revealed aneusomy of chromosome 17. Neu overexpression was found in 18% of the tumours (six cases). Five of these were aneuploid, whereas two were aneusome for chromosome 17. Four cancers showed full (normal) expression of nm23 protein, whereas 29 had reduced expression. Reduced expression was found in 23 of 25 aneuploid tumours. Numerical aberrations of chromosome 17 were found equally in carcinomas with reduced and full nm23 protein expression. Abnormal numbers of chromosome 17 seem only to have a minor impact on these markers and are not reflected significantly in their expression.

Assessing estrogen and progesterone receptor status in fine needle aspirates from breast carcinomas. Results on six years of material and correlation with biochemical assay.

OBJECTIVE: To evaluate the usefulness of immunocytochemical staining on breast fine needle aspiration (FNA) cytology as a routine procedure for determination of estrogen (ER) and progesterone (PR) receptor status. STUDY DESIGN: FNA cytology material from 864 patients was immunostained for ER and PR using Abbott ER/PR-ICA kits. Percentage of stained nuclei, staining intensity and staining pattern was evaluated. In 259 cases comparison with biochemical assay was possible. RESULTS: Of the cases, 75.6% were ER positive and 65% PR positive, and 61.6% were both ER and PR positive. Approximately 4% of the smears were inconclusive because of scant cellularity. Concordance between the immunostaining and biochemical method was 84% for ER and 71% for PR. Kappa values were 0.61 and 0.4, respectively. Major discrepancies were found in 7.7% of the specimens. CONCLUSION: Inconclusive smears due to scant cellularity is a minor problem. Technical difficulties are few, and false negative and positive staining is rarely seen. The results are comparable to those from the biochemical method, and immunostaining of ER/PR on breast cancer FNA cytology smears is useful as a routine procedure for receptor determination.

nm23 protein expression in fine-needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status, and ploidy.

BACKGROUND: nm23 has been recognized as a potential suppressor gene of metastasis. Reduced nm23 expression in breast carcinoma has been found to correlate with axillary lymph node metastases, high grade tumors, and shorter survival. METHODS: nm23 protein was detected immunocytochemically using an avidin-biotin complex technique. When a few cells showed negative or marked reduced cytoplasmic staining, expression was considered reduced. Cytologic grading was performed on routine fine-needle aspirates (FNAC). Ploidy was determined by in situ hybridization of chromosomes 6, 7, 12, and 17 on interphase cell nuclei from FNAC. When all four chromosomes revealed a disome pattern, the tumor was classified as diploid; mixed disome/aneusome carcinomas as well as those with aneusomy in all four chromosomes were considered aneuploid. RESULTS: Approximately 83% of specimens had reduced expression of nm23 protein. Forty-four of 45 lymph node positive tumors as well as 27 of 29 aneuploid tumors, were found to have reduced nm23 expression. Likewise, 49 of 57 Grade 2 (G2) carcinomas (86%) and 20 of 22 Grade 3 (G3) carcinomas (91%) showed reduced nm23 expression. Twenty-nine of 39 Grade 1 (G1) carcinomas (74%) had reduced nm23 expression. None of the G1 or G2 tumors with full nm23 expression had axillary lymph node metastases. CONCLUSIONS: nm23 protein showed a significant inverse correlation with lymph node status, cytologic grading, and ploidy. The nm23 protein antibody may have potential as a preoperative marker in identifying subgroups of patients who either may have a worse prognosis than expected (e.g., those with G1 carcinomas with reduced nm23 expression) or who may be able to avoid axillary lymph node dissection (e.g., those with G1 carcinoma with full nm23 protein expression). Cancer

Ploidy analysis by in situ hybridization of interphase cell nuclei in fine-needle aspirates from breast carcinomas: correlation with cytologic grading.

Fine-needle aspirates from 54 breast cancer patients were investigated for numeric aberrations in chromosomes 6, 7, 12, and 17 by in situ hybridization (ISH) of interphase cell nuclei. Ploidy findings were compared with cytologic grading of tumors. Aneuploidy was found in 73% of cases. Chromosomes 6 and 7 showed numeric abnormalities in 63% and 62% of cases, respectively, whereas chromosome 17 retained a disome pattern in 2/3 of the tumors. Thirteen cancers (28% of 47 with four analyzed probes) had a normal signal number in all four chromosomes. In 17 (36%), all four had signal gain. Another 17 showed a mixed disome/aneusome pattern. They presented a continuum of increasing numeric abnormalities, 82% disomy for chromosome 17, and 13 of them were grade 2, indicating intermediate biologic properties. Correlation between grading and ploidy was good, with 10 of 11 grade 1 carcinomas showing diploidy, whereas 33 of 36 grade 2 and 3 tumors had numeric aberrations.