Risk of harboring an unruptured intracranial aneurysm.

BACKGROUND AND PURPOSE: The purpose of the present study was to calculate the prevalence and relative risk of unruptured incidental intracranial aneurysms (IAs) among families with IA case(s) compared with the general population in one geographically defined area in East Finland and to identify the risk group that could benefit most from screening for IAs. We compared these results with our earlier study results of familial IA (FIA) cases, with two or more known IA cases in the same family. METHODS: The study groups were collected from the catchment area of the University Hospital of Kuopio in East Finland. The inclusion criteria were age 30 to 70 years and unruptured incidental IAs > or =3 mm. Patients with previous subarachnoid hemorrhage or in whom a ruptured IA was found to be the cause of death were excluded from all study groups. During routine forensic autopsies the circle of Willis was studied for IAs to estimate the number of IAs in the general population. In the families with one known IA case and in FIA families, MR angiography was used as a preliminary screening method for IAs, followed by intra-arterial angiography to verify suspected IAs. Study populations were age and sex adjusted for the statistical calculations. RESULTS: The relative risk for IAs among first-degree relatives in FIA families was 4.2 (95% confidence interval, 2.2 to 8.0) and among first-degree relatives in families with only one affected family member was 1.8 (95% confidence interval, 0.7 to 4.8) compared with the general population in East Finland. CONCLUSIONS: First-degree relatives in FIA families constitute a high-risk group for incidental IAs, and this group would benefit from screening studies for IAs. Screening for IAs in families with only one affected member or in the general population is not recommended.

Nucleolar organizer regions in myofibroblasts in breast cancer. Relation to cancer cell morphometry, flow cytometry, sex steroid receptor content, tumour histology and prognosis.

The number of silver-stained nucleolar organizer regions (Ag-NORs) was counted in stromal myofibroblasts in 125 cases of breast cancer. The mean (S.E.) of Ag-NORs in stromal myofibroblasts was 4.4 (0.1). The number of Ag-NORs in myofibroblasts was related to histological grade (p = 0.028), histological type (p = 0.013), tumour necrosis (p = 0.026), mitotic frequency (p = 0.091) and S-phase fraction (p = 0.032). The number of Ag-NORs in stromal myofibroblasts predicted survival with a borderline significance (x2 = 3.4, p = 0.052) and also in axillary lymph node negative tumours (X2 = 2.8, p = 0.095). The recurrence-free survival in the entire cohort (X2 = 7.1, p = 0.0075) and in axillary lymph node negative tumours (X2 = 7.1, p = 0.0078) could be predicted on the basis of the number of Ag-NORs in stromal myofibroblasts. In axillary lymph node positive tumours the number of Ag-NORs in stromal myofibroblasts had no prognostic value. In multivariate analysis the number of Ag-NORs in stromal myofibroblasts had no independent prognostic value. The results suggest a close interaction between stromal myofibroblasts and epithelial cancer cells in breast cancer, and stromal changes are clearly a subject for further analyses.

Mast cells in breast cancer.

The number of stromal mast cells was counted in 187 breast carcinomas. The number of mast cells/mm2 of tumour stroma was studied in relation to clinical, histological and quantitative prognostic factors and survival. A high number of mast cells in tumour stroma was significantly related to low S phase fraction (p = 0.001), DNA diploidy (p = 0.028), high proportion of intraductal growth (p = 0.003) and high degree of tubule formation (p = 0.044). Large tumours showed a lower number of mast cells in stroma (p = 0.08). A non-significant trend was found between mast cell count and axillary lymph node status, sex steroid receptor content, histological type, morphometric nuclear factors and mitotic frequency. In survival analysis a high mast cell count (over 10 g per mm2 of tumour stroma) was related to a favorable prognosis (p = 0.04). The present results confirm previous results in that changes in mast cell count are related to histopathological characteristics and clinical outcome in breast cancer.

Proliferating-cell nuclear antigen (PC10) immunolabelling and other proliferation indices as prognostic factors in breast cancer.

Proliferating cell nuclear antigen, PCNA (PC10), immunolabelling was determined in 175 women with breast carcinomas and related to other established prognostic factors: flow-cytometric data, volume-corrected mitotic index, sex steroid receptor content and clinical outcome during the mean follow-up of 9 years. The maximum fraction of PCNA-positive nuclei (PCNAmax), the average fraction of positive nuclei (PCNAtot) and the number of intensely stained nuclei per microscope field (PCNAcount) were significantly related to histological grade (P < 0.001), DNA ploidy ((P < 0.001), S-phase fraction (P < 0.001), mitotic index (P < 0.001) and sex steroid receptor content (P = 0.002). PCNAmax (P = 0.015) predicted survival in univariate analysis; PCNAtot (P = 0.025), PCNAmax (P = 0.007) and PCNAcount (P = 0.019) predicted the recurrence-free survival. In axillary-lymph-node-negative tumours, PCNAtot (P = 0.092), PCNAmax (P = 0.036) and PCNAcount (P = 0.006) predicted survival and recurrence-free survival (P = 0.011), (P = 0.012) and (P = 0.006) respectively. In multivariate analysis including clinical, histological, flow-cytometric and biochemical variables, PCNAtot (P = 0.004) predicted the recurrence-free survival independently. In axillary-lymph-node-negative breast cancers, PCNAtot predicted accurately the patient survival (P = 0.002) and the recurrence-free survival (P = 0.002). The results indicate that PCNA immunolabelling has independent prognostic value particularly in local breast cancer.

Young breast-cancer patients have unfavorable prognosis because of biologically aggressive tumors.

A retrospective analysis of 418 breast cancer patients was done to investigate the differencies in survival, in clinical and in histopathological variables between the different age groups giving special attention to young women. Three age groups were used, young (age less-than-or-equal-to 40 years), middle-aged (41-50 years) and elderly women (>50 years). The tumours in young women had high mitotic activity (p<0.001), high S phase fraction (p=0.025), dense lymphocyte infiltration (p=0.027), high nuclear variable values (p=0.020-0.042), bilateral disease (p=0.001) and low estrogen receptor content (p=0.013) as compared with other age groups. The prognosis of patients under the age of 40 was more unfavorable than their middle-aged counterparts (p=0.0207). The young women have more rapidly proliferating breast tumours than the middle-aged or the elderly women, and moreover the tumours are often bilateral.

DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer.

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour diameter (p < 0.001), M/V index (p = 0.006) and the year of treatment (p = 0.08) were independent predictors. The results show that tumour diameter, pN status and proliferative activity of cancer cells are important prognostic factors in breast cancer. Of the proliferation indices, M/V index and SPF are equally powerful predictors, and the use of M/V index is advocated due to simplicity of the assessment.

DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer.

Clinical features, 8 histological variables, 7 nuclear morphometric variables, 2 mitotic indices, oestrogen-receptor (ER) and progesterone-receptor content (PR), DNA ploidy and S-phase fraction (SPF) were entered in a Cox's model to assess their independent predictive value in 216 breast-cancer patients followed up for over 9 years. In the whole series, histological type (p = 0.007), volume-corrected mitotic index (M/V index) (p = 0.01), axillary-lymph-node (pN) status (p = 0.024) and the year of treatment (p = 0.045) predicted independently the recurrence-free survival (RFS). In a sub-analysis including SPF (n = 148), the year of treatment (p = 0.003), tumour diameter (p = 0.004), SPF (p = 0.022) and nuclear pleomorphism (p = 0.056) independently predicted the RFS. In a Cox's analysis of the whole series, tumour diameter (p less than 0.001), pN status (p = 0.001), PR status (p = 0.002) and the year of treatment (p = 0.021) were independent predictors of survival. In a separate analysis including also SPF (n = 148), tumour diameter (p less than 0.001), SPF (p = 0.003), pN status (p = 0.008) and the year of treatment (p = 0.015) proved to be independent prognostic factors. The results show that tumour diameter, pN status, M/V-index, histological type, SPF and PR status comprise a sufficient combination of prognostic factors in female breast cancer. In pN patients, age and SDPE may be of additional prognostic significance. The prognostic scores combining the independent prognostic variables reflecting both the proliferative rate and metastatic potential of the tumours are accurate predictors of the RFS and overall survival.

Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer.

S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). Recurrence-free survival (RFS) was significantly related to SPF only in ER+ (p = 0.001) and PR+ (p less than 0.001) tumours. In survival analysis, ER+ (p = 0.002) and PR+ (p less than 0.001) patients were efficiently divided into prognostic groups by SPF, whereas in ER- and in PR- tumours SPF had only suggestive predictive value. In N- tumours, SPF predicted recurrence-free survival and disease-related survival in ER+ (p = 0.003) (p = 0.039) and in PR+ (p = 0.003) (p = 0.012) tumours, respectively, whereas in ER-, PR-, tumours, SPF had no predictive value. In pN+ tumours, SPF also predicted survival in ER+ (p = 0.03) and in PR+ (p = 0.024) tumours. Thus the prognosis of ER+ or PR+ tumours with an SPF less than 9% is favourable with a risk of death of about 20%, in contrast to that of about 70% in tumours with an SPF greater than 9% during the follow-up period. To conclude, the proliferation rate as measured by S phase fraction by FCM is a highly significant prognostic factor in breast cancer. The prognostic value of S phase fraction is confined to steroid receptor-positive tumours, whereas in receptor-negative tumours SPF has no predictive value. The results thus suggest that all women with steroid receptor-negative breast tumours and those receptor-positive tumours with an SPF higher than 9% should be subjected to postoperative adjuvant chemotherapy immediately.

Nuclear morphometry and DNA flow cytometry as prognostic factors in female breast cancer.

OBJECTIVE: To evaluate the predictive value of traditional prognostic factors, nuclear morphometry, and flow cytometric data in invasive breast cancer. DESIGN: Open study. SETTING: One university hospital in Finland. SUBJECTS: 248 women with invasive breast cancer followed up for more than 11 years. MAIN OUTCOME MEASURES: Univariate and multivariate analysis of factors thought to indicate prognosis. RESULTS: Diameter of the tumour, lymph node status, S phase fraction. DNA index, the age of the patient, and the SD of nuclear perimeter were significant independent predictors in the whole series in a multivariate analysis. In node negative patients the SED of the nuclear perimeter and diameter of the tumour had independent prognostic value, whereas in node positive patients diameter of the tumour and the S phase fraction were independently related to survival. CONCLUSIONS: Diameter of the tumour is an important prognostic factor in breast carcinomas. Histoquantitative methods are superior to conventional histological techniques for the prediction of outcome in women with breast cancer.