Axillary Lymph Node Negative Tumours Research Articles

Absence of tolerance to cataleptic activity of gamma-hydroxybutyric acid after subchronic administration to male mice

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.

Nimodipine attenuates psychotigenic effects of ketamine in humans

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.

Expression of insulin-like growth factor I (IGF-I) in female breast cancer as related to established prognostic factors and long-term prognosis.

The expression of insulin-like growth factor I (IGF-I) was analysed immunohistochemically in a series of 211 breast cancers with special emphasis on its relationship to conventional prognostic factors and long-term prognosis. Altogether, IGF-I was expressed by the tumour cells in 91% of the breast carcinomas, and by stromal cells in 29%. The expression of IGF-I in cancer cells was weakly related to a high proportion of intraductal growth (P = 0.032), distinct tumour margins (P = 0.048) and high S-phase fraction (P = 0.074). In a univariate analysis, IGF-I expression in cancer cells was significantly related to a high survival probability in the entire cohort (P = 0.0144) as well as in the axillary lymph node positive tumours (P = 0.0286). Alternatively, expression of IGF-I in the stromal cells was related to metastasis at the time of diagnosis (P = 0.05), tumour diameter (P = 0.04), DNA ploidy (P = 0.07) and nuclear pleomorphism (P = 0.025), but it was without prognostic significance in a univariate analysis (P > 0.1). In a multivariate analysis, the conventional prognostic factors were superior to IGF-I expression in predicting the disease outcome, albeit expression of IGF-I in tumour stroma showed some independent prognostic significance in axillary lymph node negative tumours. The results suggest that IGF-I expression is related to malignant histopathological features in breast cancer, and expression of IGF-I has independent prognostic significance in the early phases of the disease.

Expression of E-cadherin (E-CD) as related to other prognostic factors and survival in breast cancer.

A series of 208 breast cancer biopsies were analysed immunohistochemically for expression of E-cadherin (E-CD). Altogether, 72 per cent of the tumours showed E-CD positivity in over 50 per cent of cells, the staining being heterogeneous in nearly all tumours. In only 16 per cent of ductal carcinomas was positive staining seen in less than 1 per cent of cells. Expression of E-CD was not related to tumour diameter, nodal status, metastasis at diagnosis, histological grade, DNA ploidy, S-phase fraction, nuclear area, mitotic frequency, or PR content. There was a significant relationship between expression of E-CD, histological type (P = 0.01), the proportion of intraductal growth (P = 0.008), the density of tumour-infiltrating lymphocytes (P = 0.0007), ER content (P = 0.012), and morphometric nuclear factors (P < 0.02). Expression of E-CD showed a weak association with a high survival probability (P = 0.02), while the relation to recurrence-free survival was not significant (P = 0.1). In axillary lymph node-negative tumours, E-CD expression was not related significantly to survival (P = 0.11) or to recurrence-free survival (P = 0.06). In multivariate analysis, E-CD expression had no independent prognostic value, while the axillary lymph node status, tumour diameter, patient age, and mitotic frequency were independent prognostic factors. The results indicate that E-CD expression is related to several histological features in breast cancer, but has no independent prognostic value over standard prognostic factors.

Apoptosis in breast cancer as related to histopathological characteristics and prognosis

Apoptotic cells were quantitated by light microscopy in a series of 288 breast carcinomas, and their number (cells/ mm 2 of neoplastic epithelium, i.e., the apoptotic index, AI) was related to various histopathological features and disease outcome. High AI was associated with tumour necrosis ( P = 0.003), lack of tubule formation ( P = 0.03), dense stromal lymphocyte infiltration ( P = 0.0009), high grade of the tumour ( P < 0.0001), DNA aneuploidy ( P = 0.049), high S-phase fraction ( P = 0.010), high mitotic rate ( P < 0.0001), lack of sex steroid receptors ( P = 0.004), expression of p53 tumour suppressor gene ( P = 0.004), and high values of morphometrically measured nuclear factors ( P < 0.05). In survival analysis, an AI greater than 3/mm 2 was related to short recurrence-free survival in the entire cohort ( P = 0.0079) as well as in the axillary lymph node-negative tumours ( P = 0.0253). Survival of the patients with node-negative rumours ( P = 0.0356), node-positive tumours ( P = 0.0085) and in the entire cohort ( P = 0.004) was related to AI. Recurrence-free survival was related to the mitotic index ( P = 0.0012), ductal type ( P = 0.011), S.D. of the nuclear area ( P = 0.075), and axillary lymph node status ( P = 0.096). Cox's analysis showed that only the tumour diameter ( P < 0.001), axillary lymph node status ( P = 0.001), progesterone receptor content ( P = 0.004) and ductal type ( P = 0.041) had independent prognostic value, whereas AI did not.

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.

Nucleolar Organizer Regions Related to Morphometry, Flow Cytometry, Sex Steroid Receptor Content, Tumour Histology and Prognosis in Female Breast Cancer

Nuclear organizer regions (Ag-NORs) were visualized and enumerated in biopsy specimens from 158 breast carcinomas and the results were correlated with clinical, histological, quantitative prognostic factors and survival. The number of Ag-NORs was related significantly to histological type (p = 0.003), tubule formation (p = 0.013), histological grade (p < 0.001), mean nuclear area (p < 0.001), SD of nuclear area (p < 0.001), DNA ploidy (p < 0.001), S phase fraction (p = 0.001), mitotic index (p < 0.001), estrogen receptor content (p < 0.001) and progesterone receptor content (p < 0.001). Ag-NORs were independent of tumour size and axillary lymph node status. Neither in the entire cohort (p = 0.16) nor in axillary lymph node negative tumours (p = 0.11) was the number of Ag-NORs related to survival although a clear trend was observed between lowered survival probability and high Ag-NOR count. In multivariate analysis Ag-NORs had no independent prognostic value. The results confirm previous results in that Ag-NORs have no practical prognostic value over already established prognostic factors in breast cancer.

Lymphocyte infiltrates as a prognostic variable in female breast cancer

The predictive value of lymphocyte infiltrates (LI) was studied in 489 patients with breast cancer followed-up for over 10 years. LI were positively correlated to axillary lymph-node status, tumour diameter and histological and morphometric variables ( P < 0.001). In a multivariate analysis LI were independently related to axillary lymph-node status. LI predicted recurrence-free survival (RFS) in rapidly proliferating tumours ( P = 0.0269). LI predicted RFS ( P = 0.08) and breast cancer related survival (BS) ( P = 0.0164) in rapidly proliferating, axillary lymph-node negative tumours. In a multivariate analysis LI independently predicted BS ( P = 0.08) in rapidly proliferating tumours. LI independently predicted BS in rapidly ( P = 0.025) and slowly ( P = 0.09) proliferating, axillary lymph-node negative tumours. If the tumours were not categorised according to proliferation rate, LI and outcome were not significantly related. The results clearly confirm the presence of efficient immunological antitumour defence mechanisms in human breast cancer. Consequently tumour-host interactions are subject to further studies particularly in axillary lymph-node negative breast cancer.

Histological assessment of the prognostic factors in female breast cancer.

Paraffin-embedded biopsy specimens from the primary breast carcinoma of 653 women were subjected to histopathological assessments of the potential prognostic factors. Histological type, histological grade, nuclear pleomorphism, tubule formation, intraductal growth pattern, tumour margin circumscription, tumour necrosis and inflammatory cell reaction were semiquantitatively analysed with special reference to disease outcome during the mean follow-up 12.8 years. Histological grade, nuclear grade and inflammatory cell reaction were related to axillary lymph node involvement at operation (p less than 0.001). Intensity of the inflammatory cell reaction was directly correlated to histological grade, histological type, nuclear pleomorphism and tumour necrosis (p less than 0.001). Tubule formation and tumour necrosis were significant predictors for tumour recurrence. Recurrence-free survival was related to tubule formation (p = 0.0048), histological grade (p = 0.0208) and intraductal growth pattern (p = 0.0441). Tubule formation accurately predicted the recurrence-free survival in axillary lymph node-negative tumours (p = 0.0386). In small (diameter less than or equal to 20 mm) axillary lymph node-negative tumours, the inflammatory cell reaction (p = 0.0377) as well as intraductal growth pattern (p = 0.0632) were related to recurrence-free survival. Cancer-related patient survival was predicted in decreasing order of significance by tubule formation (p = 0.0002), nuclear pleomorphism (p = 0.0010), intraductal growth (p = 0.0077), tumour necrosis (p = 0.0117) and histological type (p = 0.0651). In axillary lymph node-negative tumours, tubule formation (p = 0.0409), inflammatory cell infiltration (p = 0.0790) and intraductal growth (p = 0.0958) predicted the cancer-related survival. The results indicate that despite an intense search for a diversity of prognostic factors by increasingly sophisticated techniques (e.g., morphometric measurements, flow cytometry, immunohistochemistry, and DNA hybridization techniques), the relatively simple light microscopic assessment of the above morphological features seems to be still advocated in predicting the disease outcome in female breast cancer.

Hormone Receptors as Prognostic Factors in Female: Breast Cancer

The oestrogen (ER) and progesterone receptor (PR) status in a series of 281 women with breast cancer (followed up for a mean of 8.5 years) was correlated with eight histological variables, seven nuclear morphometric factors and two mitotic indices. Sex steroid receptor status was not significantly related to tumour size, axillary lymph node status or tumour recurrence. Sex steroid receptors were related to histological grade (P less than 0.0001), nuclear grade (P less than 0.0001), tumour necrosis (P = 0.0003), tumour circumscription (P = 0.0027), inflammatory cell reaction (P = 0.007), intraductal growth pattern (P = 0.0378), and tubule formation (P = 0.0432). Receptor status was also significantly related to nuclear morphometric variables (P less than 0.001) and mitotic indexes (P less than 0.001). In univariate analysis, ER (P = 0.2) and PR (P = 0.1) negatively predicted the recurrence free survival. Cancer related survival was predicted by ER (P = 0.0068) and PR (P = 0.0027). In small (diameter less than or equal to 2 mm) axillary lymph node negative tumours, ER (P = 0.09) and PR (P = 0.1) had some value in predicting the survival. The survival advantage of steroid receptor positive tumours was not due to adjuvant hormone therapy. Sex steroid receptors had independent predictive value in multivariate survival analysis and also in small (diameter less than or equal to 20 mm) tumours. The results indicate that sex steroid receptor negativity is related to several malignant histological features in breast cancer and hormone receptors have prognostic value. Their prognostic influence seems to be mediated through the different proliferation rates in receptor positive and negative breast carcinomas.