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The influence of familial and hereditary factors on the prognosis of breast cancer.

BACKGROUND: Family history is a well recognized risk factor for breast cancer, but its impact in terms of breast cancer survival is uncertain. The recent identification of breast cancer predisposing genes has provided new clinical insights in this field. DESIGN: English literature identified through Medline between 1976 and February 1999 was reviewed including search terms: breast cancer, survival, prognosis, family history, genetics, BRCA1, BRCA2, and related articles. RESULTS: Publications were divided into three categories. Family history-based studies: eighteen articles were reviewed. Four studies showed a statistically significant better survival in patients with a family history of breast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. LINKAGE STUDIES: Two studies based on linkage to BRCA1 found that overall survival was better in linked families. A third one concluded to a worse outcome in BRCA2-linked tumors. MUTATION-BASED STUDIES: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcomes were reviewed. Eight articles reported no significant difference in outcome, whereas two studies showed a worse outcome in patients with mutations. CONCLUSIONS: Conflicting data exist as to whether the prognosis of familial or hereditary breast cancer differs from that of sporadic cases. Some of the discrepancies may be explained by methodological differences or biases. However, no studies showed a survival advantage for BRCA1 mutation carriers. This seems to indicate that BRCA1-related breast cancer is not associated with a survival advantage, and that in fact, certain BRCA1 germline mutations confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsible for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.

BRCA2 Protein↗

Prognosis of patients with lung cancer diagnosed in Norway, 1954-93.

Lung cancer is the most common cancer in the world today, and the prognosis for lung cancer patients is poor. In the Nordic countries, the five-year relative survival was only seven percent in patients diagnosed in 1983-87. In the present study, the survival of 36,010 lung cancer patients diagnosed in Norway in 1954-93 was examined, based on data from the population-based Cancer Registry of Norway. The variation in survival by gender, age, stage, period of diagnosis, and histologic group was explored. Relative survival rates were calculated and relative risks of dying were obtained from multivariate Cox proportional hazards regression analysis. Only a slight improvement in the prognosis of lung cancer patients was observed during the 40-year study period. More than half the patients died during the first six months after diagnosis. Patients with small cell carcinoma had the lowest frequency of localized tumors and also had the poorest prognosis, even after adjustment for stage. Patients with squamous cell carcinoma had the highest frequency of localized tumors. The patients with a localized tumor also have a poor prognosis, with a crude median survival time of nine months in males and 11 months in females in 1984-93.

Adolescent↗

Does perioperative blood transfusion influence long-term prognosis of gastric cancer?

We analyzed the influence of packed red blood cell (PRBC) transfusions on the prognosis of 163 patients with gastric adenocarcinoma undergoing subtotal gastrectomy with a curative intention. Over a period of 15 years, our department admitted 505 patients with gastric adenocarcinoma, with curative subtotal gastrectomy being performed in 167 cases. Mean age was 62.2 years (range: 30-87); there was a predominance of males (104 cases; 63.8%). Excluding the four patients who died in the immediate postoperative period (first 30 days), the remaining 163 were reviewed twice yearly in our department until either they died or the study ended. Follow-up averaged 49.5 months, with a median of 36 months. Sixty-nine (42.3%) of the 163 patients received transfusions of PRBC. On correlating the variables with the transfusion, we found a statistical significance only between the rate of transfusion and patient age over 63 years (P < 0.01), with an evolution time of less than three months (P < 0.05) and in tumors of >4 cm (P < 0.05). The five-year survival rate of the nontransfusion patients was 56.9% and of the transfusion patients 40%, with statistically significant differences (P = 0.0132). On studying patients according to tumor stage, we found that blood transfusion had a statistically significant influence on prognosis only in patients with tumor stage III (P = 0.0051). In the univariate analysis of the remaining variables collected, the existence of abdominal tumor (P = 0.0307), tumor size (P = 0.00001), degree of involvement of the gastric wall (P = 0.00001), lymph node involvement (P = 0.00001) and tumor stage (P = 0.00001) revealed a statistically significant influence on prognosis. If we apply Cox's regression model to the variables that in the univariate analysis had a statistically significant influence on prognosis, we found that only tumor size and stage were independent predictors of survival. In our experience, PRBC transfusion does not influence the long-term survival of patients with resected gastric adenocarcinoma.

Adenocarcinoma↗

Minichromosome maintenance 2 expression is correlated with mode of invasion and prognosis in oral squamous cell carcinomas.

BACKGROUND: This study examined the immunohistochemical expression of cell-cycle related molecules as well as cell proliferation and pathologic findings in oral squamous cell carcinoma (SCC) in order to clarify their pathobiologic and prognostic significance. METHODS: A total of 46 oral SCC specimens were analyzed using Ki-67, minichromosome maintenance 2 (MCM2), p53, p27, p21, and TUNEL. Aspects including tumor differentiation, mode of carcinoma invasion, tumor metastasis, and patient prognosis were compared among the specimens. RESULTS: A significantly higher MCM2 labeling index (LI) was observed in the moderately differentiated SCCs when compared to the well-differentiated SCCs (P<0.05). The higher MCM2 LI was correlated with mode of invasion Grade 4 (infiltrative growth) and patient prognosis. In contrast, the LIs of Ki-67, TUNEL-signal, p53, p27, and p21 were not correlated with patient prognosis. CONCLUSION: Higher MCM2 LI provides useful information for patient prognosis in oral SCCs.

Carcinoma, Squamous Cell↗

Poor prognosis for malignant melanoma in Northern Ireland: a multivariate analysis.

All cases of cutaneous malignant melanoma, CMM, diagnosed in Northern Ireland between 1974-1978 were reviewed, classified and followed up until the end of 1984. The overall 5 year survival is 54%, among the worst reported in recent literature. Multivariate analysis of these cases confirms some previous findings from other studies, but also reveals features not apparent in univariate analysis. Prognosis worsens with increasing thickness and the presence of ulceration. Likewise histopathological type has an independent effect on survival, ALM having the worst prognosis. Tumour profile emerges as a significant feature affecting prognosis, flat lesions having the poorest outlook, given their thickness. Survival is worse with increasing age. Anatomical site is less important than suggested by previous univariate analysis. Sex has little influence on prognosis when adjusted for the other variables. Cell type and pigmentation are of no prognostic value. Several features including diagnostic delay contribute to the poor overall survival for CMM in Northern Ireland. Educational intervention is essential if this trend is to be reversed.

Female↗

Evaluation of p53 protein expression as a marker for long-term prognosis in colorectal carcinoma.

Mutation of the p53 gene is reported to be of prognostic importance in colorectal carcinomas. Immunohistochemical staining of the accumulated p53 gene product may be a simple alternative for p53 mutation analysis. Previous studies addressing the prognostic importance of p53 expression, however, yielded contradictory results. Therefore, we evaluated the importance of p53 expression as a marker for long-term prognosis in a well-characterised study population of 109 colorectal carcinomas. After antigen retrieval with target unmasking fluid (TUF), immunostaining of p53 was performed with both monoclonal antibody DO7 and polyclonal antibody CM1. Objective quantification of the p53 signal was assessed by a computerised image analyser. p53 expression was higher in non-mucinous tumours than in mucinous tumours (p53 labelling index = 30% and 17% respectively, P = 0.05), and in metastatic tumours compared with non-metastatic tumours (p53 labelling index = 37% and 22% respectively, P = 0.05). Other histopathological features were not related to p53 expression. In multivariate analysis, Dukes' stage (P = 0.02) and histological grade (P = 0.05) stood out as independent markers for prognosis. p53 expression was not an independent marker for prognosis. At present, p53 expression is not a useful marker for long-term prognosis. Further insight into the relationship between p53 mutations and p53 expression is needed to elucidate more precisely the clinical relevance of p53 alterations.

Adult↗

Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer.

If oesophageal carcinoma is detected in the superficial stage, the prognosis is better than for advanced oesophageal carcinoma. But the factors which predict the prognosis and treatment policy remain unclear. Matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) have been reported to have close associations with tumour invasion and metastasis. In this study, we retrospectively studied the relations between MMP-7 and MMP-9 expression in immunohistochemistry, clinicopathologic factors, and prognosis in 55 superficial oesophageal carcinomas. MMP-7 and MMP-9 expression occurred in 23.6% and 47.3% of the patients, respectively. MMP-7 expression was significantly correlated with the presence of nodal metastasis (P=0.004). MMP-9 expression was significantly correlated with the depth of tumour invasion (P=0.004), lymphatic permeation (P=0.001), nodal metastasis (P=0.049), and pathologic differentiation grade (P=0.003). By the log-rank test, MMP-7 expression and MMP-9 expression on the invasive front were related to the prognosis. In multivariate analysis, MMP-9 expression on the invasive front was an independent prognostic indicator. The combined expression of MMP-7 and MMP-9 may be a good marker for the degree of malignancy of oesophageal cancer and for the presence of lymphatic metastasis.

Adenocarcinoma↗

Low expression of polypeptide GalNAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma: impact on poor prognosis and early recurrence.

Initial glycosylation of mucin-type O-linked protein is catalysed by one of the UDP-GalNAc: polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3). O-glycosylation is important in the binding of cell adhesion molecules, cell differentiation, invasion, and metastasis in tumours. This study was designed to detect GalNAc-T3 expression in lung adenocarcinoma by using immunohistochemical staining, and to evaluate the relationship between the GalNAc-T3 expression level and prognosis and recurrence in completely resected lung adenocarcinoma patients. A low expression of GalNAc-T3 was detected in the cytoplasm of tumour cells in 79 of 148 patients (53.4%) with lung adenocarcinoma. The low expression of GalNAc-T3 was associated with poorly differentiated tumour (P<0.0001), poor pathologic stage (P<0.0001), lymph node metastasis (P<0.0001), and tumour recurrence (P=0.016). The lung carcinoma patients with low GalNAc-T3 expression had a poorer prognosis than those with high GalNAc-T3 expression, using both univariate and multivariate analyses (overall survival: P<0.0001 and P=0.011, respectively). In addition, multivariate analysis of the clinicopathological characteristics of stage I lung adenocarcinoma indicated that the low expression of GalNAc-T3 was a significant independent factor for predicting poor prognosis and early recurrence (P=0.006, rr=2.87 and P=0.019, rr=3.05, respectively). The low expression of GalNAc-T3 may be a useful marker for predicting poor prognosis and early recurrence in completely resected lung carcinoma patients, particularly patients with stage I diseases.

Adenocarcinoma↗

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis.

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.

Adenocarcinoma↗

Expression of pyrimidine nucleoside phosphorylase mRNA plays an important role in the prognosis of patients with oesophageal cancer.

To clarify the significance of the expression of pyrimidine nucleoside phosphorylase (PyNPase) mRNA as a predictive factor for the prognosis of patients with oesophageal carcinoma, the PyNPase mRNA in the tumours and normal tissues from 55 resected cases of oesophageal carcinoma was examined by a reverse transcription polymerase chain reaction (RT-PCR). As a result, a positive correlation was observed between the tumour/normal (T/N) ratio of the expression of PyNPase mRNA by RT-PCR and that of the enzyme activity of PyNPase based on the findings of an enzyme linked immunosolvent assay (r = 0.594, P = 0.009). The T/N ratio of the expression of PyNPase mRNA was significantly higher in the cases with lymph vessel invasion (P = 0.013), lymph node metastasis (P = 0.0016), and an advanced stage of the disease (P = 0.021) than those without these factors. The patients with a higher T/N ratio of PyNPase mRNA showed significantly worse prognosis than those with a lower T/N ratio (P = 0.023 with log-rank tests). A multivariate analysis for the cumulative survival rates revealed that a high T/N ratio of the expression of PyNPase mRNA was independently related to a poor prognosis. These findings suggested that the determination of PyNPase mRNA by RT-PCR thus appears to be a new useful parameter for identifying both a poor prognosis and a highly malignant potential of oesophageal carcinoma.

Adult↗

Long-term follow-up of patients with poor prognosis germ cell tumor treated with early high-dose chemotherapy with hematopoietic progenitor cell support: a single-center experience.

The 5-year overall survival rate of patients with germ cell tumor (GCT) with poor prognosis, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification, is 48% after standard-dose chemotherapy and surgery, if necessary. Two recent studies have showed that early high-dose chemotherapy (HDCT) with hematopoietic progenitor cell support (HPCS) may induce a 2-year overall survival rate of 78% in these patients. We report the long-term results of the experience at the Department of Oncology in Ravenna with early HDCT and HPCS in GCT patients with poor prognosis (IGCCCG criteria). Between 1987 and 2002, 18 poor prognosis GCT patients (17 M, one F), median age 24.5 years (range, 17-52), were treated with early HDCT with HPCS. In total, (67%) patients achieved a complete remission and they are continuously disease-free at a median follow-up of 9.2 years (range, 1.7-16.2). One treatment-related death occurred. No patient developed myelodysplasia or a secondary leukemia. This is notably the longest follow-up reported in patients having received HDCT in this setting. No patient achieving a complete remission relapsed. The role of HDCT in poor prognosis GCT will be defined from the ongoing phase III randomized trials.

Adolescent↗

The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients with Graves' disease.

OBJECTIVE: The relationship between emotional stress and the onset of hyperthyroidism has been well investigated, but the relationship between psychological factors and prognosis of antithyroid drug-treated hyperthyroidism is not well known. This study has examined not only emotional stresses but also patients' personality traits using specific tests. DESIGN: A prospective cohort study. SUBJECTS: Sixty-nine patients with hyperthyroid Graves' disease in the euthyroid state after 2-5 years of antithyroid drug therapy and 32 healthy subjects as the control group. MEASUREMENTS: Patients responded to three types of questionnaires, including the Minnesota Multiphasic Personality Inventory for personality traits, the Natsume's Stress Inventory for major life events, and the Hayashi's Daily Life Stress Inventory for daily life stresses. RESULTS: In the Graves' disease patients, stress scores of life events correlated significantly with serum TSH receptor antibody activity (r = 0.424, P < 0.001) and thyroid volume (r = 0.480, P < 0.001). When the patients were divided according to prognosis (41 with relapse and 28 with remission), four personality traits including hypochondriasis, depression, paranoia and psychasthenia (mental fatigue) were significantly (P = 0.0146, 0.0052, 0.0125, and 0.0186, respectively) more common in the relapsed Graves' disease group than those of the remitted group. Six personality traits of conversion hysteria, psychopathic deviation, masculinity and feminity, schizophrenia, hypomania, and social introversion were not significantly different between the two groups. The scores of daily hassles (problems of daily life) were also significantly (P = 0.0124) greater in the relapsed Graves' disease group than in the remitted group. The scale scores of depression and psychasthenia showed a positive correlation with scores of daily hassles (r = 0.535, P < 0.0001; r = 0.580, P < 0.0001, respectively), while an inverse correlation with scores of daily uplifts (r = -0.373, P = 0.0332; r = -0.322, P = -0.0120, respectively). CONCLUSIONS: The results suggest that major life events, personality traits of hypochondriasis and depression, paranoia, mental fatigue, and daily problems aggravate the prognosis of antithyroid drug-treated hyperthyroidism. Escape from life events is virtually impossible; thus coping strategies suggested by the physician may be useful in improving prognosis in Graves' disease.

Adult↗

Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV-infected squamous cell carcinoma and adenocarcinoma of the lung.

AIMS: The infiltration of Langerhans cells in adenocarcinomas and squamous cell carcinomas of the lung was examined in relation to prognostic implications and human papillomavirus (HPV) infection. METHODS AND RESULTS: Samples from 62 adenocarcinoma and 59 squamous cell carcinoma patients in 1995-97, the prognosis of which had been followed up, were used. The Langerhans cells were demonstrated immunohistochemically using anti S100a and CD1 antibodies. Human papillomavirus (HPV) infection was examined by polymerase chain reaction (PCR) and nonisotopic in-situ hybridization (NISH) methods. Statistical analysis was carried out using the Kaplan-Meier method (Wilcoxon analysis) and multiple regression analysis. HPV infection was demonstrated in 12 cases (19.4%) of adenocarcinoma. The HPV-infected adenocarcinomas had abundant faintly eosinophilic cytoplasm, and were immunohistochemically positive for the surfactant apoprotein A. In the 59 cases of squamous cell carcinomas 19 were of the well differentiated form, and 29 and 11 were moderately and poorly differentiated cases, respectively. HPV was detected in 29 cases (49.2%) (13 well and 16 moderately differentiated cases). In all HPV-infected adenocarcinoma and squamous cell carcinoma cases, extremely large numbers of Langerhans cells (more than 100 per high-power field) were demonstrated in the tumour nests. In contrast, in the non-HPV-infected adenocarcinomas and squamous cell carcinomas, only a few (less than about 10 per high-power field) Langerhans cells were observed. The squamous cell carcinoma cases with high Langerhans cell infiltration, which were also infected with HPV, showed a significantly good prognosis (P = 0.007). The adenocarcinoma cases with high Langerhans cell infiltration tended to have a better prognosis than the cases with low Langerhans cell infiltration, but the difference was not statistically significant. The low number of highly infiltrated cases was insufficient for an adequate statistical analysis. Furthermore, there was no significant correlation between either Langerhans cell infiltration and smoking, or HPV infection and smoking, in either squamous cell carcinoma or adenocarcinoma cases. CONCLUSIONS: It was considered that the extremely high Langerhans cell infiltration in the tumours was caused by HPV infection. The extremely large number of Langerhans cells in the tumours contributes to the favourable prognosis for HPV-infected lung cancer.

Adenocarcinoma↗

Combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma.

AIMS: In order to estimate the prognostic values of p27(Kip1), p21(Waf1/Cip1), and p53, alone and in combination, we investigated immunohistochemically the expression of p27(Kip1), p21(Waf1/Cip1), and p53 proteins in gastric carcinomas. METHODS AND RESULTS: The expression of p27(Kip1), p21(Waf1/Cip1), and p53 was immunohistochemically examined in 140 gastric carcinomas. Positive expression of p27(Kip1) and p21(Waf1/Cip1) correlated significantly with a favourable prognosis (P < 0.05), whereas, positive expression of p53 tended to correlate with poor prognosis. Multivariate survival analysis revealed that TNM stage of tumour (P < 0.001), lymph node state (P=0.005), and p27(Kip1) expression (P=0.006) were independent prognostic factors. A striking stratification of mortality rate was found when patients were divided into four groups according to the expression of p21(Waf1/Cip1) and p27(Kip1). The mortality rate was higher in patients with both p21(Waf1/Cip1)- and p27(Kip1)-negative gastric carcinoma than in patients with one or both positive carcinomas (P < 0.01). In addition, if the four p21(Waf1/Cip1)/p27(Kip1) groups were compared based on p53 status, p53+ cases tended to have a higher mortality rate than p53- cases. CONCLUSION: Our results suggest that low expression of both p27(Kip1) and p21(Waf1/Cip1), could be useful as markers of poorer prognosis, and the combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows reliable estimation of prognosis for patients with gastric carcinoma.

Adult↗

ALK-negative anaplastic large-cell lymphoma demonstrates similar poor prognosis to peripheral T-cell lymphoma, unspecified.

AIMS: Anaplastic large cell lymphoma (ALCL) is classically considered a clinicopathological entity separate from other nodal mature T-cell lymphomas (TCL). Recently, the anaplastic lymphoma kinase (ALK) protein was shown to identify a subgroup of nodal ALCL with an excellent prognosis, whereas ALK-negative ALCLs are more heterogeneous. The aim of this study was to investigate the clinicopathological parameters in relation to clinical behaviour of ALK-negative ALCL compared with other nodal mature TCL, i.e. peripheral TCL, unspecified (PTCL-NOS) and angioimmunoblastic lymphoma (AILT). METHODS AND RESULTS: Clinicopathological data of ALK-positive (n = 28) and ALK-negative (n = 46) ALCL; PTCL-NOS (n = 47); and AILT (n = 12) were analysed for their prognostic significance. While ALK-positive ALCL shows favourable clinical features and a good prognosis, ALK-negative ALCL, PTCL-NOS and AILT are all associated with high age groups, advanced disease stage, and poor prognosis (<45% 5-year survival). In multivariate analysis of overall survival time, performed in the combined group of ALK-negative nodal mature T-cell lymphomas, only age and the International Prognostic Index (IPI) remained independent prognostic parameters, while lymphoma subtype (ALCL versus PTCL-NOS versus AILT) gave no additional information. CONCLUSIONS: The distinction between ALK-negative ALCL and PTCL-NOS or AILT is of limited clinical relevance as they show comparable poor prognosis. In these lymphoma subtypes, only age and the IPI are of significant prognostic value.

Adolescent↗

Independent importance of psychosocial factors for prognosis after myocardial infarction.

AIMS: As a primary aim it was tested whether the 10-year prognosis after a myocardial infarction is related to psychological stress, lack of social support, anxiety, and/or depressive tendency. A secondary aim was to analyse the prognostic importance of a series of other psychosocial factors as well as interactions. METHODS: Non-selected patients aged below 65 years with a first infarction (230 men and 45 women) were followed for 10 years with 100% assessment of morbidity and cause-specific mortality. Baseline somatic and psychosocial variables were collected with the aid of standard, validated questionnaires. RESULTS: In multivariate analysis, factors increasing risk for coronary mortality included female sex (hazard ratio, +/- 95% confidence interval) 2.47 (1.06, 5.71), signs of left ventricular failure 3.93 (1.87, 8.26), ventricular dysrhythmia 3 months after the infarction 5.45 (2.21, 13. 42), high depression scores 3.16 (1.38, 7.25) and lack of social support 2.75 (1.29, 5.89). All-cause mortality was significantly related to left ventricular failure, ventricular dysrhythmias, and high depression scores with borderline significance for female sex and social support. Prognosis was affected during the entire follow-up period. It was not significantly associated with age, marital status, education, extra work, mental strain at work or in the marriage, anxiety, dissatisfaction with family life, problems with children, dissatisfaction with the financial situation, life events, anger-in, irritability, type A behaviour, or health locus of control. Incidence of nonfatal infarction was not associated with any of the baseline variables. CONCLUSION: In addition to known somatic predictors of prognosis after a myocardial infarction, prognosis is strongly influenced by depression and lack of social support, but not to a series of other psychosocial factors. It is recommended to use self-reporting scales to detect prognostically important psychosocial problems.

Adult↗

High topoisomerase IIalpha expression associates with high proliferation rate and and poor prognosis in oligodendrogliomas.

The role of molecular markers predicting the prognosis and the selection of patients for further adjuvant therapies is not well established in oligodendroglioma patients. A potential prognostic as well as a therapeutically predictive factor, topoisomerase IIalpha (topoIIalpha), is a molecular target for certain cytotoxic drugs. Its expression has been shown to correlate with the prognosis in a number of different cancers and with the chemosensitivity of cancer cells in vitro. The expression of topoIIalpha was evaluated immunohistochemically in 59 oligodendrogliomas and in 29 mixed gliomas with a predominating oligodendroglioma component by the use of a tissue microarray technique. In the gliomas, the percentage of topoIIalpha immunopositive cells protein expression varied from 0.0 to 49.1% (5.2 +/- 8.3%, mean+/- SD). In oligoastrocytomas, the mean topoIIalpha score was significantly higher in the oligodendroglioma than in the astrocytoma component of the tumour (5.37 +/- 5.58% vs. 1.89 +/- 2.49%, P = 0.018). A significant association was found between the high proportion of topoIIalpha positive cells and high grade of the tumour (P < 0.0001), high tumour proliferation rate (P < 0.0001), p53 overexpression (P = 0.01) and high expression of tumour suppressing retinoblastoma protein (P = 0.023). TopoIIalpha expression was not associated with the age or sex of patient, and the rate of apoptosis. TopoIIalpha expression associated highly significantly with patient prognosis; a significantly higher proportion of patients with low rather than with high topoIIalpha score was alive at the end of the 5-year follow-up (P = 0.03). Cox analysis was used to demonstrate that topoIIalpha had an independent prognostic value for survival (P = 0.034). In conclusion, high topoIIalpha expression characterizes oligodendrogliomas and oligoastrocytomas which are poorly differentiated, have high proliferation rate, and has prognostic value for overall survival of these patients. Therefore, topoIIalpha may be a useful marker for better targeted selection of poor prognosis oligodendroglioma patients for adjuvant therapy.

Adolescent↗

Tubular carcinoma of the breast: prognosis and response to adjuvant systemic therapy.

BACKGROUND: Tubular carcinoma of the breast is an uncommon and usually small tumour, and is thought to have a favourable prognosis. The present study examined the long-term prognosis of patients with tubular breast carcinoma and the roles of axillary dissection and adjuvant therapy. METHODS: Eighty-six tubular cases were identified from a large worldwide database of 9520 breast carcinoma patients entered into randomized adjuvant therapy trials run by the International Breast Cancer Study Group from 1978 to 1999. These patients were followed for a median of 12 years. RESULTS: Forty-two (49%) cases were node-positive, of which 33 (79%) had 1-3 nodes involved. Ten (32%) of the 31 smaller tumours (< or = 1 cm in size) were node-positive. Patients with node-positive tubular carcinoma had a significantly better 10-year relapse-free survival (P = 0.006) and survival (P < 0.0001) compared with non-tubular node-positive cases. Overall survival was similar for node-positive and node-negative tubular carcinoma. Overall, 71 patients (83%) received some form of adjuvant systemic therapy. Of the 86 cases, 43 (50%) received more than one course of chemotherapy. There was an 85% decrease in the risk of death for patients who received more than one course of chemotherapy compared to those who did not (hazard ratio 0.15, 95% confidence interval (CI): 0.03-0.82; P = 0.03). CONCLUSIONS: Compared to other histological types of breast cancer, tubular carcinoma has a better long-term prognosis. Adjuvant chemotherapy may further improve prognosis and involvement of axillary nodes may not be an indicator for early death due to breast carcinoma.

Adenocarcinoma↗