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H Nordgren

Publications and source records attributed to H Nordgren.

At least 19 recordsLinked to original sources
PubMed2006

Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.

AIM: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. SETTING: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. METHODS: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. RESULTS: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (kappa=0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. CONCLUSION: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area.

Breast Neoplasms↗
PubMed2005

Expression of EGFR, HER2, HER3, and HER4 in metastatic squamous cell carcinomas of the oral cavity and base of tongue.

The expressions of all four receptors in the epidermal growth factor receptor family, EGFR. HER2, HER3, and HER4 were evaluated by immunohistochemistry in 19 cases of metastatic squamous cell carcinoma of the oral cavity and base of tongue. EGFR had a similar and high expression in both primary tumours and the corresponding metastases, while the expression in normal epithelium was lower in most cases. HER2 was not expressed to the same extent as EGFR. However, when HER2 was well expressed, it was in most cases expressed to the same extent and intensity in the primary tumours, metastases, and normal epithelium. The expression of HER3 and HER4 varied and was mainly cytoplasmic in all cases studied. No overexpression of HER3 and HER4 in tumours was seen as compared to normal epithelium. In order to further investigate the distribution of HER3, two HER3 expressing cell lines originating from tongue cancer were analysed in vitro, using radiolabelled anti-HER3 antibodies directed to the extracellular domains of the receptor. The results indicated that HER3 was not present in measurable amounts in the cellular membrane. There is a need for improved diagnostics and therapy for the studied type of tumours, e.g. using radiolabelled antibodies or ligands, and EGFR seemed suitable as target since the expression was high, membrane associated and similar in the primary tumours and the corresponding metastases.

Aged↗
PubMed2004

HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review.

The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.

Breast Neoplasms↗
PubMed2004

Oral cancer after using Swedish snus (smokeless tobacco) for 70 years - a case report.

Whereas the smoking habit has declined significantly in Sweden in recent decades, there has been a marked increase in the consumption of 'snus' (oral moist snuff). The use of this smokeless tobacco, exposing the user locally to carcinogenic nitrosamines, raises the question - will the increasing use of snuff eventually lead to a greater incidence of oral cancer? We report the case of a 90-year-old man who developed a localized squamous cell carcinoma in the gingival fold under the upper lip, at the exact place where he had regularly placed loose oral snuff for 70 years. Although this is a reminder of a prevailing cancer risk, the time frame indicates that the risk is slight. This is consistent with recent epidemiological reports regarding the minor risk of snuff-associated cancer in the Scandinavian countries.

Aged↗
PubMed2003

Risk factors for local recurrence after breast-conserving surgery.

BACKGROUND: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. METHOD: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. RESULTS: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. CONCLUSION: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.

Adult↗
PubMed2002

Ductal carcinoma in situ of the breast: a new phenotype classification system and its relation to prognosis.

In a study of invasive breast cancer, multiple correspondence analysis (MCA) revealed clustering of eight pathobiological variables. Two different phenotypes were distinguished by an index calculated on the basis of the variables (histologic grade, necrosis, lymphoid infiltration, number of mitosis and expression of c-erbB-2, p53, progesterone receptor and Bcl-2). Phenotype A lesions share most of the features of normal breast tissue. Phenotype B looks more malignant, has a higher early recurrence rate and is more frequently seen in younger patients. Our aim was to see if ductal breast carcinoma in situ (DCIS) could be divided into the same phenotypes. One hundred and eighty DCIS were investigated. Association between the eight variables was studied in 2 x 2 models. The phenotype index was calculated by summing weights for the variables in the MCA. All variables were associated, except Bcl-2. DCIS was divided in two phenotypes. Thirty-three tumours were Phenotype A and 147 Phenotype B. The mean age at diagnosis was 65.5 and 58.4 years for Phenotypes A and B, respectively (p = 0.0012). No difference regarding local relapse free survival was seen. Two phenotypes were distinguished in DCIS, similar to invasive breast cancer. In an earlier study, 45% of the invasive cancers were classified as Phenotype B. In this study, 82% of DCIS were Phenotype B. This may indicate that invasive breast cancer of Phenotype B is derived from DCIS of Phenotype B. The distribution of DCIS phenotypes with a small proportion of Phenotype A DCIS may be due to that Phenotype A DCIS is less likely to be detected by mammography, or that some invasive breast cancers of Phenotype A progress to invasiveness without passing the in situ phase.

Adult↗
PubMed2001

Increased p53 mutation frequency during tumor progression--results from a breast cancer cohort.

The mutational patterns of the p53 gene for exons 4-9 were analyzed in 30 recurring tumors compared with the p53 status of the corresponding 30 primary breast cancers. The prevalence of p53 mutations was higher, although not statistically significant (P = 0.07), in the evaluable recurring tumors compared with the corresponding primaries, 12 of 29 (41%) versus 7 of 30 (23%). Twenty-one of the patients had unchanged p53 mutation status in the recurring compared with the primary tumors, whereas 8 had an altered mutational status or pattern in the sequential tumor. These findings indicate that p53 mutations may be an important factor for tumor progression in human breast cancer.

Breast Neoplasms↗
PubMed2001

Tumour markers in breast carcinoma correlate with grade rather than with invasiveness.

Ductal breast carcinoma in situ (DCIS) is regarded as a precursor to invasive breast cancer. The progression from in situ to invasive cancer is however little understood. We compared some tumour markers in invasive and in situ breast carcinomas trying to find steps in this progression. We designed a semi-experimental setting and compared histopathological grading and tumour marker expression in pure DCIS (n = 194), small invasive lesions (n = 127) and lesions with both an invasive and in situ component (n = 305). Grading was done according to the Elston-Ellis and EORTC classification systems, respectively. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, ER, PR, bcl-2 and angiogenesis. All markers correlated with grade rather than with invasiveness. No marker was clearly associated with the progression from in situ to invasiveness. The expression of tumour markers was almost identical in the 2 components of mixed lesions. DCIS as a group showed a more 'malignant picture' than invasive cancer according to the markers, probably, due to a higher proportion of poorly differentiated lesions. The step between in situ and invasive cancer seems to occur independently of tumour grade. The results suggest that well-differentiated DCIS progress to well-differentiated invasive cancer and poorly differentiated DCIS progress to poorly differentiated invasive cancer.

Biomarkers, Tumor↗
PubMed2000

Local breast cancer recurrence caused by mammographically guided punctures.

PURPOSE: To evaluate the risk of needle track seeding or tumor cell implantation as the cause of locally recurrent breast cancer after breast conserving surgery. MATERIAL AND METHODS: We reviewed recurrences from a consecutive series of 303 clinically nonpalpable breast cancers treated with breast conserving surgery after pre-operative localization. The median mammographic follow-up was 5.4 years. The suspicion of seeding or implantation was based on the location of the recurrent lesion in comparison with the needle path in two orthogonal mammographic projections. Pre-operative percutaneous biopsies had been done in 71% (214/303) of the cases. Postoperative radiotherapy was administered to 82% (194/238) of the invasive cancers and to 28% (18/65) of the ductal cancers in situ (DCIS). RESULTS: Locally recurrent cancer occurred in 11% (33/303) of the cases. Radiotherapy demonstrated a protective effect from relapse among invasive cancers but not for DCIS. Seeding or implantation was suspected in 3 recurrent invasive cancers which had not been subject to radiotherapy. The histopathological diagnosis of the primary cancer and the recurrent cancer were the same in these cases: adenoid cystic, mucinous and tubuloductal cancer. CONCLUSION: Seeding or implantation was suspected as the cause of local recurrence in 7% (3/44) of the invasive cancers which did not receive radiotherapy.

Adenocarcinoma↗
PubMed1999

A comparative study of apoptosis and necrosis in HepG2 cells: oxidant-induced caspase inactivation leads to necrosis.

Apoptosis and necrosis are two distinct forms of cell death that can occur in response to various agents. In the present study the HepG2 cell line was used for a comparative study of CD95-mediated apoptosis and menadione-induced necrosis. Apoptosis coincided with the release of cytochrome c from mitochondria, activation of caspases, cleavage of cellular proteins, and also involved nuclear condensation and DNA fragmentation. Necrosis was not accompanied by DNA fragmentation, caspase activation or cleavage of caspase target proteins, despite cytochrome c release from mitochondria. In fact, the addition of menadione to cells undergoing CD95-mediated apoptosis blocked their caspase activity. Inhibition of caspases coincided with an accumulation of reactive oxygen species (ROS) and ATP depletion. In order to determine the predominance of either of these events in the inhibition of caspase, cells were either co-incubated with antioxidant enzymes or their ATP level was manipulated to maintain it at a relatively high level during the experiments. Co-incubation with catalase, but not Cu/Zn superoxide dismutase, substantially reduced the levels of ROS and reversed the inhibitory effect of menadione on caspase activity. In contrast, increasing cellular ATP level had little effect on restoring caspase activity. These data suggest that menadione inhibits caspase activity by the generation of hydrogen peroxide through redox cycling and that caspase inactivation by this mechanism may prevent cell death by apoptosis in this oxidative-stress model.

Apoptosis↗
PubMed1999

Ductal carcinoma in situ of the breast from a population-defined cohort: an evaluation of new histopathological classification systems.

The increased incidence of ductal carcinoma in situ of the breast (DCIS) in the era of mammography screening requires a deeper knowledge of the biology of the disease and calls for a suitable classification system to optimise therapy. Our aim was to evaluate the correlation to prognosis for two new classification systems of DCIS. The histopathological specimens from 195 women consecutively diagnosed between 1986 and 1994 with a primary DCIS were re-classified by two separate observers using the system proposed by an European Organization for Research and Treatment of Cancer (EORTC) working group and the Van Nuys system. The relapse-free survival (RFS) by histopathological subgroup and by nuclear grade only was estimated for women treated with breast conserving surgery (n = 149). Thirty-two local recurrences occurred among 149 women (mean follow-up time 59 months). No distant recurrences or breast cancer deaths were reported. The women in the group with the highest differentiation according to the EORTC classification had no recurrences. RFS did not differ appreciably between the two other groups. This was true also after stratification for radiotherapy. We found no statistically significant difference in RFS between the three groups in the Van Nuys classification. There was an overall agreement between the observers in 79% and 64% of the cases, according to the EORTC and Van Nuys systems, respectively. We were able to define one group with highly differentiated lesions and an excellent prognosis with the EORTC classification. Further classification into intermediate and low differentiated lesions did not help predict RFS.

Adult↗
PubMed1999

10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial.

PURPOSE: To study the long-term effectiveness of postoperative radiotherapy after sector resection for breast cancer in a randomized trial in which mammography is a major pathway to diagnosis. PATIENTS AND METHODS: Three hundred eighty-one women with a unifocal breast cancer < or = 20 mm in diameter on the preoperative mammogram and without histopathologic signs of axillary metastases were treated by sector resection plus axillary dissection. Of these patients, 184 women were randomized to receive postoperative radiotherapy to the breast (XRT group), and 197 women received no further treatment (non-XRT group). RESULTS: The local recurrence rate was 8.5% (95% confidence interval [CI], 3.9% to 13.1%) in the XRT group and 24.0% (95% CI, 17.6% to 30.4%) in the non-XRT group (P =.0001). Survival free from regional and distant recurrence was 83. 3% in the XRT group (95% CI, 77.5% to 89.1%) and 80.0% in the non-XRT group (95% CI, 73.9% to 86.1%) (P =.23). Overall survival was 77.5% in the XRT group (95% CI, 70.9% to 84.1%) and 78% in the non-XRT group (95% CI, 71.7% to 84.3%) (P =.99). A subgroup analysis suggested that women older than 55 years of age without comedo or lobular carcinomas had a low risk of local recurrence of 6.1% (95% CI, 0.1% to 9.1%) in the XRT-group and 11.0% (4.0% to 18.0%) in the non-XRT group (P =.16). CONCLUSION: Sector resection plus radiotherapy resulted in an absolute reduction in local recurrence of 16% at 10 years compared with surgery alone. Women older than 55 years of age without comedo or lobular carcinomas may have a low risk of local recurrence. Postoperative radiotherapy was not shown to reduce distant recurrences or improve overall survival.

Breast Neoplasms↗
PubMed1998

Value of sextant biopsies in the assessment of local cure following external beam radiotherapy of prostatic adenocarcinoma.

Between 1982 and 1992, 73 patients received radical external beam radiotherapy (EBR) for prostatic adenocarcinoma at the Central Hospital, Västerås, with an average dose of 68.1 Gy (range 64.5-72.5 Gy) and an average cumulative radiation effect (CRE) of 18.2 (range 17.1-19.9) All patients had a negative bone scan prior to treatment and presented with clinical stage T1-T4,Nx,Mo. Twenty-four out of 36 surviving patients consented to participate in a follow-up study which included transrectal, ultrasonically guided prostate biopsies. The average follow-up from EBR to biopsy was 5.5 years (range 3.6-11.1 years). Sixteen (67%) of the patients had a positive biopsy. The average PSA level in the biopsy-positive group was 35.7 ng/mL (range 3.9-200 ng/mL). In the biopsy-negative group, the average PSA was 3.7 ng/mL (range 0.2-13.0 ng/mL). The conclusion is that the degree of local cure achieved in patients with prostatic cancer treated with external beam radiotherapy is low (33%), and that a higher radiation dose may be required to eradicate this malignancy.

Adenocarcinoma↗
PubMed1997

Risk factors for local recurrence after conservative treatment in stage I breast cancer. Definition of a subgroup not requiring radiotherapy.

BACKGROUND: Risk factors for local recurrence after breast-conserving treatment of early breast cancer have not previously been evaluated in settings where mammography has been a major pathway to diagnosis of both primary tumour and recurrences or in patients treated surgically by a formal sector resection. PATIENTS AND METHODS: Three hundred eighty-one women with stage 1 primary breast cancer were randomised after a standardised sector resection to either a course of postoperative radiotherapy to 54 Gy to the breast (XRT group) or to surgery alone (non XRT group). At five years, 43 local recurrences, six of them in the XRT group, appeared. Patient characteristics collected from the medical records, histopathological characteristics determined by re-examination of slides, and mammographic characteristics from the pre-operative mammograms were evaluated as risk factors for recurrence by univariate and multivariate Cox proportional hazards models. Results are reported as relative hazards (RH) with 95% confidence intervals (95% CI). RESULTS: In the univariate analysis comedo cancer, RH 3.5 (95%, CI 18 6.7), lobular cancers RH 2.8 (95% CI 1.1 7.1), mammographic appearance as circular/oval shaped density, RH 2.3 (95% CI 1.1 4.51, and mammographic appearance as a stellate lesion with microcalcifications inside the lesion, RH 3.8 (95% CI 1.1-13.0) were identified as risk factors for local recurrence. Age, with a RH of 0.97 (95% CI 0.94 0.99) for each increasing year was inversely associated with risk. A multivariate analysis, which also took postoperative radiotherapy into account, only showed comedo cancers with a RH 2.6 (95% CI 1.3-5.0) and mammographic appearance of a stellate lesion with microcalcification inside the lesion RH 4.5 (95% CI 1.1-17.6) to be statistically significant. The estimates for age RH 0.98 (95% CI 0.95 1.01 and lobular cancers RH 2.5 (95%, CI 0.98 6.6) were marginally changed, with widened CIs. Patients > 60 years of age, without comedo or lobular carcinomas were found to be at low risk 15.9% at five years in Kaplan Meyer estimate) of local recurrence, even without postoperative radiotherapy. CONCLUSION: Low age, comedo and lobular cancers and mammographic appearance of the tumour as a stellate lesion with microcalcifications inside the lesion indicate an increased risk for local recurrence after sector resection in stage 1 tumours at five years. Patients > 60 years of age without comedo or lobular cancers are at low risk for local recurrence at five years even without postoperative radiotherapy.

Combined Modality Therapy↗
PubMed1997

E4, a new monoclonal antibody identifying a human prostatic cell surface antigen

The monoclonal antibody E4 (IgG2a, kappa) was raised by immunizing mice with dispersed cells obtained from human benign prostatic hyperplasia (BPH). The antibody identifies an antigen abundantly expressed in normal prostate epithelial cells, in benign epithelial prostatic cells and in well- and moderately well differentiated adenocarcinomas of the prostate, whereas poorly differentiated prostatic adenocarcinomas display somewhat less expression. Investigation of the human prostatic adenocarcinoma cell line DU 145 revealed E4 immunoreactivity localized to the cell surface. SDS-PAGE analysis under reducing conditions demonstrated an approximate molecular weight of 70,000 for the antigen. The highly specific reactivity with prostate tissue, as well as intense surface staining, especially in well- and moderately well differentiated prostatic adenocarcinomas, makes the E4 antibody a useful immunohistochemical marker and a possible candidate for future immunoscintigraphy and/or targeted radiotherapy.

Journal Article↗
PubMed1996

The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry.

BACKGROUND: Mutations in the p53 tumor suppressor gene (also known as TP53) have been detected in a wide variety of human cancers. In breast cancer, the presence of p53 gene alterations has been associated with worse prognosis. PURPOSE: We compared a complementary DNA (cDNA)-based sequencing method and an immunohistochemical (IHC) method for their abilities to detect p53 mutations in breast cancer specimens. In addition, we determined the prognostic value of information obtained when these two methods were used. METHODS: Specimens from 316 primary breast tumors were evaluated for the presence of mutant p53 protein by use of the mouse monoclonal antibody Pab 1801 (that recognizes both wild-type and mutant forms of p53) and standard IHC methods. In addition, the entire coding region of p53 genes expressed in these tumors was screened for mutations by combining reverse transcription, the polymerase chain reaction, and DNA sequencing. Probabilities for overall survival (OS), breast cancer-corrected survival (BCCS; death from breast cancer is the considered event), and relapse-free survival (RFS) were estimated by use of the Kaplan-Meier method, and survival curves for different patient subgroups were compared by use of the logrank method. All reported P values are from two-sided tests. RESULTS: Sixty-nine (22%) of 316 tumors had p53 gene mutations detected by the cDNA-based sequencing method; only 31 (45%) of these mutations were located in evolutionarily conserved portions of the p53 coding region. Sixty-four tumors (20% of the total) had elevated levels of p53 protein as detected by IHC, suggesting the presence of mutations. Of the sequencing-positive tumors (i.e., p53 mutant), 23 exhibited negative IHC reactions, indicating that IHC failed to detect 33% of the mutations. Furthermore, 19 of the IHC-positive tumors were sequencing negative (i.e., p53 wild-type), suggesting a 30% false-positive frequency with IHC. Four tumors (1.3% of the total) could not be analyzed by the cDNA-based sequencing method, and three tumors (1% of the total) could not be analyzed by IHC. The 5-year estimates for RFS, BCCS, and OS were significantly shorter for patients with p53 sequencing-positive tumors than for patients with sequencing-negative tumors (P = .001, P = .01, and P = .0003, respectively). Patients with IHC-positive tumors showed reduced survival in all three categories when compared with those with IHC-negative tumors, but the differences were not statistically significant. CONCLUSIONS: Use of a cDNA-based sequencing method to determine the status of the p53 gene in primary breast cancers yielded better prognostic information than IHC performed with the Pab 1801 monoclonal antibody.

Adult↗
PubMed1996

Bcl-2 immunoreactivity in prostate tumorigenesis in relation to prostatic intraepithelial neoplasia, grade, hormonal status, metastatic growth and survival.

The Bcl-2 protein prolongs cell survival by overriding apoptosis. To explore the role of Bcl-2 in prostate tumorigenesis, immunoreactivity for Bcl-2 was examined in untreated and androgen-deprived tumours and lymph node metastasis. Following the transurethral resection, 150 untreated patients were maintained under surveillance until death or for a minimum of 11 years, and castration was performed at symptomatic progression. The Bcl-2 index (BI) was defined as the percentage of immunoreactive cells in a tumour. The mean BI was 12 in the untreated tumours, and BI was significantly higher in high-grade tumours, mean BI 17, than in low-grade tumours, mean BI 6. There was no correlation between BI and stage or metastatic disease, nor did BI predict cancer-specific survival. In 16 androgen-deprived, but non-relapsed tumours, the mean BI was 54, at a mean time of 22 months after castration, indicating a permanent increase of Bcl-2 protein expression after androgen withdrawal. In six patients, tissues from the prostate tumour and obturator lymph node metastasis were available. Four primary tumours immunostained for Bcl-2, but only one metastasis stained. Foci of highgrade prostatic intraepithelial neoplasia (PIN) were present in 44 of the 150 untreated tumours. All PIN foci were intensely immunoreactive for Bcl-2, and mean BI was 79, suggesting that Bcl-2 protein expression is associated with early prostate tumorigenesis.

Aged↗