Berit Sandstad

CD10 protein expression in tumor and stromal cells of malignant melanoma is associated with tumor progression

CD10 antigen is a 100-kDa-cell surface zinc metalloendopeptidase expressed in a variety of normal and neoplastic lymphoid and nonlymphoid tissues including melanomas. It was recently shown that metastatic melanomas express more CD10 than primary tumors. We evaluated CD10 expression in tumor and stromal cells in 70 biopsies with primary and 28 with metastatic malignant melanomas. Ki-67, Bcl-2, and Bax were also examined to investigate whether CD10 expression is associated with tumor proliferation index or factors of apoptosis. Formalin-fixed/paraffin-embedded tissues were studied by immunohistochemistry. More advanced primary tumors had higher CD10 expression in the tumor cells (r=0.27, P=0.03 for Clark levels and r=0.29, P=0.02 for Breslow) and higher Ki-67 proliferation fraction (r=0.32, P=0.007 for Clark levels and r=0.32, P=0.001 for Breslow). Similarly, CD10 expression in the intratumoral stromal cells was also higher in primary tumors with higher Clark level (P=0.04, linear-by-linear association) and tumor thickness according to Breslow (r=0.33, P=0.01). The presence of CD10+ peritumoral stromal cell cuffs was also positively associated with tumor thickness according to Breslow (r=0.27, P=0.05). Also, expression of CD10 and Ki-67 were significantly higher in metastatic than in primary tumors (P=0.01 and 0.02 respectively), but Bcl-2 expression was higher in primary melanomas (P=0.02). We conclude that CD10 expression in malignant melanoma is associated with tumor progression.

The impact of ADHD and conduct disorder in childhood on adult delinquency: A 30 years follow-up study using official crime records

BackgroundFew longitudinal studies have explored lifetime criminality in adults with a childhood history of severe mental disorders. In the present study, we wanted to explore the association between adult delinquency and several different childhood diagnoses in an in-patient population. Of special interest was the impact of disturbance of activity and attention (ADHD) and mixed disorder of conduct and emotions on later delinquency, as these disorders have been variously associated with delinquent development.MethodsFormer Norwegian child psychiatric in-patients (n = 541) were followed up 19-41 years after hospitalization by record linkage to the National Register of Criminality. On the basis of the hospital records, the patients were re-diagnosed according to ICD-10. The association between diagnoses and other baseline factors and later delinquency were investigated using univariate and multivariate Cox regression analyses.ResultsAt follow-up, 24% of the participants had been convicted of criminal activity.In the multivariate Cox regression analysis, conduct disorder (RR = 2.0, 95%CI = 1.2-3.4) and hyperkinetic conduct disorder (RR = 2.7, 95% CI = 1.6-4.4) significantly increased the risk of future criminal behaviour. Pervasive developmental disorder (RR = 0.4, 95%CI = 0.2-0.9) and mental retardation (RR = 0.4, 95%CI = 0.3-0.8) reduced the risk for a criminal act. Male gender (RR = 3.6, 95%CI = 2.1-6.1) and chronic family difficulties (RR = 1.3, 95% CI = 1.1-1.5) both predicted future criminality.ConclusionsConduct disorder in childhood was highly associated with later delinquency both alone or in combination with hyperactivity, but less associated when combined with an emotional disorder. ADHD in childhood was no more associated with later delinquency than the rest of the disorders in the study population. Our finding strengthens the assumption that there is no direct association between ADHD and criminality.

Iron status in a group of Norwegian children aged 6-24 months

An adequate iron status is of vital importance for health and development in infancy and early childhood. Iron status was evaluated in a group of full‐term Norwegian children followed longitudinally, at the ages of 6 mo (n= 278), 12 mo (n= 249) and 24 mo (n= 231) by measuring haemoglobin (Hb), mean cell volume (MCV) and serum ferritin. At 6, 12 and 24 mo of age, 3, 10 and 12%, respectively, had iron deficiency anaemia (IDA) defined as Hb <110 g/l in combination with ferritin <15 μg/l. With more restrictive criteria for defining IDA 10 μg/l) increased from 2 to 3% at 6 mo, from 5 to 7% at 12 mo and from 9 to 13% at 24 mo.

The role of secondary cytoreduction in the management of the first relapse in epithelial ovarian cancer

BACKGROUND The aim of this study was to investigate the benefit of secondary cytoreduction (SCR) in the first relapse in epithelial ovarian cancer and to attempt to define selection criteria for SCR. PATIENTS AND METHODS A retrospective population-based study on recorded information from 789 patients treated at the Norwegian Radium Hospital during 1985-2000 for their initial recurrence. In all, 217 had SCR and 572 were treated with chemotherapy alone. RESULTS Median survival time (MST) was 1.1 years for the chemotherapy group. Complete optimal cytoreduction (COC) was achieved in 35% of all 217 patients, in 49% of the patients operated with debulking intent and in 52% if bowel surgery was done with debulking intent. MST was 4.5 versus 0.7 years for 0 versus>2 cm residual disease, respectively. Residual disease after SCR, treatment-free interval (TFI) and age were found to be prognostic factors for overall survival (OS) in multivariate analysis. Localised tumour was found to be the only significant factor to predict COC. CONCLUSIONS SCR followed by chemotherapy gives a clear survival benefit compared with chemotherapy and should be offered when the tumour is localised. The combination of COC, TFI >24 months and age </=39 years identifies a group of patients with the best OS.

Occult Metastases in Axillary Lymph Nodes as a Predictor of Survival in Node-Negative Breast Carcinoma with Long-term Follow-up

Abstract:  Increased detection rate in the lymph nodes is seen with serial sectioning or immunohistochemistry (IHC), but the importance of occult metastases is not resolved. IHC is still not recommended in routine examination of lymph nodes. Axillary lymph nodes from 385 node‐negative breast cancer patients with a median follow‐up of 25 years were examined with IHC for cytokeratins, applied on routine sections. The association between classic histopathologic prognostic factors and the presence of occult metastases was evaluated. Metastases were found in 45 of 385 cases (12%), 21 metastases (47%) measured ≤0.2 mm, 8 (18%) were larger than 2 mm; 14 metastases were located in the subcapsular sinus, 22 in the parenchyma of the lymph node; and 51% (23/45) of the metastases were recognized on hematoxylin‐eosin staining on “second look.” The detection of metastases was significantly associated with the number of sectioned lymph nodes (6% metastases for one to five lymph nodes examined versus 17% for more than five lymph nodes) and with histologic subtype (metastases in 11% of the ductal versus 33% of the lobular carcinomas). No significant association was found between occult metastases and age, tumor size, histologic grade, estrogen or progesterone receptor status, p53, or c‐erbB‐2. Metastases larger than 2 mm predicted a poorer recurrence‐free survival rate for the whole series. A subcapsular location of the metastases was a strong predictor of overall survival. Whether or not the metastases could be identified on hematoxylin‐eosin sections did not have any prognostic significance. In the multivariate analysis, histologic grade, tumor size of the primary tumor, progesterone receptor status, and the presence of occult metastasis in the lymph nodes had a prognostic impact on survival with a 25‐year follow‐up.

Disseminated tumour cells as a prognostic biomarker in colorectal cancer

Background:The study was performed to determine detection rate and prognostic relevance of disseminated tumour cells (DTC) in patients receiving curatively intended surgery for colorectal cancer (CRC).Methods:The study population consisted of 235 patients with CRC prospectively recruited from five hospitals in the Oslo region. Bone marrow (BM) aspirates were collected at the time of surgery and the presence of DTC was determined by two immunological methods; immunomagnetic selection (using an anti-EpCAM antibody) and immunocytochemistry (using a pan-cytokeratin antibody). Associations between the presence of DTC and metastasis-free, disease-specific and overall survival were analysed using univariate and multivariate methods.Results:Disseminated tumour cells were detected in 41 (17%) and 28 (12%) of the 235 examined BM samples by immunomagnetic selection and immunocytochemistry, respectively, with only five samples being positive with both methods. The presence of DTC was associated with adverse outcome (metastasis-free, disease-specific and overall survival) in univariate and multivariate analyses.Conclusion:The presence of DTC was associated with adverse prognosis in this cohort of patients curatively resected for CRC, suggesting that DTC detection still holds promise as a biomarker in CRC.

Nuclear S100A4 is a novel prognostic marker in colorectal cancer

Current staging classifications in colorectal cancer are not able to accurately predict patient outcome, and the need for novel prognostic markers is evident. S100A4 is a Ca(2+)-binding protein which promotes metastasis in several tumour types, and the aim of the present study was to investigate the prognostic impact of S100A4 expression in colorectal cancer. Two hundred and forty two patients with curatively resected adenocarcinoma of the colon or rectum were prospectively included in the study at the time of surgery. S100A4 expression was analysed by immunohistochemistry, and associations with clinicopathological variables and patient outcome were investigated. Nuclear expression of S100A4 was observed in 29% and cytoplasmic expression was observed in 64% of the tumours. In univariate analysis, nuclear S100A4 was a negative predictor of metastasis-free (P=0.006) and overall survival (P=0.01), whereas cytoplasmic S100A4 was not associated with patient outcome. In multivariate analysis, nuclear localisation was inversely associated with metastasis-free (P=0.03) and overall survival (P=0.02). Interestingly, the prognostic impact was largely confined to TNM stage II, and stage II patients with tumours expressing nuclear S100A4 had a similar prognosis as stage III patients. In conclusion, nuclear expression of S100A4 is a novel prognostic marker in colorectal cancer, and the prognostic value in TNM stage II suggests that nuclear S100A4 could be used in the stratification of stage II patients for adjuvant treatment.

Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium

BACKGROUND We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index. PATIENTS AND METHODS High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium. RESULTS Patients with diploid (N = 728), aneuploid tumor with DNA index ≤1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis. CONCLUSIONS The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.Background: We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index. Patients and methods: High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium. Results: Patients with diploid (N = 728), aneuploid tumor with DNA index ≤1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis. Conclusions: The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.

The Prognostic Impact of Hormone Receptors and c-erbB-2 in Pregnancy-Associated Breast Cancer and Their Correlation with BRCAI and Cell Cycle Modulators

A population-based series of 122 patients with pregnancy-associated breast carcinomas was histologically revised and the relationship between hormone receptors, cerbB-2, BRCA1, p27, cyclin E, and cyclin D1 was studied. The 5-year overall survival was 41%; 70% had tumor size >20 mm; 72% had metastasized to regional lymph nodes; 95% were histologic grade II or III; 66% and 75% were negative for estrogen and progesterone receptor, respectively; and c-erbB-2 expression was high (44%). BRCA1 expression was reduced in 33% of the cases. The expression of p27, cyclin D 1, and cyclin E was low, 11%, 9%, and 16%, respectively. Cyclin D I was positively associated with the hormone receptors (p<0.01). In multivariate analysis, lymph node status, progesterone receptor, and c-erbB-2 were significant prognostic factors. In subdividing the group according to lymph node status, c-erbB-2 and progesterone receptor retained a prognostic significance in the node positive group only. In conclusion, pregnancy-associated breast carcinomas are aggressive tumors, with low expression of hormone receptors, BRCA1, p27, and cyclin E and DI, and high expression of c-erbB-2.

Naproxen and Acetylsalicylic Acid in the Treatment of Pauciarticular and Polyarticular Juvenile Rheumatoid Arthritis Assessment of Tolerance and Efficacy in a Single-centre 24-week Double-blind Parallel Study

Naproxen (NAP) (10 mg/kg/day) and acetylsalicylic acid (ASA) (75 mg/kg/day) were compared in a 24-week randomized block, controlled, parallel, double-blind study in 80 patients with pauciarticular or polyarticular juvenile rheumatoid arthritis. Five NAP-treated compared with 20 ASA-treated patients stopped therapy because of adverse reactions. Both drug regimens seemed to be therapeutically effective. The outcome of the study indicated that ASA may have a slight advantage over NAP with regard to efficacy. However, the changes in disease activity measurements were similar in the two treatment groups.