Patrik Hesselius

Sick of Your Colleagues' Absence?

We utilize a large-scale randomized social experiment to identify how coworkers affect each others effort as measured by work absence. The experiment altered the work absence incentives for half of all employees living in Goteborg, Sweden. Using administrative data we are able to recover the treatment status of all workers in more than 3,000 workplaces. We first document that employees in workplaces with a high proportion treated coworkers increase their own absence level significantly. We then examine the heterogeneity of the treatment effect in order to explore what mechanisms are underlying the peer effect. While a strong effect of having a high proportion of treated coworkers is found for the nontreated workers, no significant effects are found for the treated workers. These results suggest that pure altruistic social preferences can be ruled out as the main motivator for the behaviour of a nonnegligible proportion of the employees in our sample.

High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study

BackgroundHuman papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates.MethodsWe compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR.ResultsHPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy).ConclusionOnly HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma.

Vacancy Referrals, Job Search, and the Duration of Unemployment: A Randomized Experiment

One goal of the public employment service is to facilitate matching between unemployed job seekers and job vacancies; another goal is to monitor job search so as to bring search efforts among the unemployed in line with search requirements. The referral of job seekers to vacancies is one instrument used for these purposes. We report results from a randomized Swedish experiment where the outcome of referrals is examined. To what extent do unemployed individuals actually apply for the jobs they are referred to? Does information to job seekers about increased monitoring affect the probability of applying and the probability of leaving unemployment? The experiment indicates that a relatively large fraction (one third) of the referrals do not result in job applications. Information about intensified monitoring causes an increase in the probability of job application, especially among young people. However, we find no significant impact on the duration of unemployment.

HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancer

The incidence of lung cancer is increasing throughout the world and is the most common cause of cancer-related death. Early detection followed by surgery has a reasonable, curative potential, but 30-50% of patients experience relapses. The immunohistochemical expressions of HER-2, EGFR and COX-2 were investigated in 53 resected non-small cell lung carcinomas and correlated to microvessel density and clinical data. HER-2, EGFR and COX-2 overexpressions were demonstrated in 15%, 30% and 40% of the tumours, respectively. In adenocarcinomas, HER-2 and COX-2 overexpression were more common, whereas in squamous cell carcinomas, EGFR overexpression was more common. COX-2 expression correlated with HER-2 expression (p = 0.002), and demonstrated a trend towards a correlation with microvessel density (p = 0.10). None of the markers alone had any impact on survival. However, HER-2+/EGFR- tumours proved to have a poor prognosis. In conclusion, adjuvant treatment with HER-2 antagonists might be a future treatment option in resected non-small cell lung cancer patients, especially when HER-2 is overexpressed without a concomitant overexpression of EGFR.

Serological and immunohistochemical analysis of S100 and new derivatives as markers for prognosis in patients with malignant melanoma.

The incidence of cutaneous malignant melanoma is rising, and tumour markers are attracting attention as a possible alternative to clinical examination in the follow-up situation. S100 is the preferred marker for malignant melanoma, and correlation between serum S100 and disease relapse and survival has been reported. S100 tests previously used in clinical studies were specified poorly regarding reactivity with S100A1B and S100BB. In this study, a newly designed S100 assay (designed to measure exclusively S100A1B and S100BB) and two newly developed serological assays, S100A1B, and S100BB, were investigated postoperatively in patients undergoing radical surgery for cutaneous malignant melanoma. Additionally, immunohistochemical analysis of S100A4 was performed on the primary malignant melanoma using tissue microarrays. The primary aim of the study was to investigate whether any of these assays, either singly or in combination, can contribute additional information concerning increased risk of relapse and death because of malignant melanoma. In total, 98 patients (54 males, 44 females) with malignant melanoma were included in the study. As a continuous variable, S100BB (P=0.016) was associated statistically with increased risk of relapse; this was not the case for increased values of either S100 (P=0.11) or S100A1B (P=0.92). The Kaplan–Meier overall survival as well as disease specific survival curve for the S100 serum level demonstrated a statistically significant association with better survival if the patient had a S100 level ≤150 ng/l (P<0.001). Survival analyses for S100A1B using a defined cutoff of 50 ng/l showed a statistically significant association concerning overall and disease specific survival (P<0.001). Furthermore, S100BB was associated with overall and disease specific survival using a defined cutoff of 50 ng/l (P<0.001). No statistically significant correlation was found between S100A4 and overall survival (P=0.96) and there was no correlation between elevated levels of S100 and the immunohistochemical staining of S100A4 (P=0.1), nor for serum S100A1B (P=0.1) nor serum S100BB (P=0.17). Circulating S100A1B and S100BB are potential biomarkers in patients with malignant melanoma. S100BB should be considered as the preferred biomarker, showing potential in predicting both relapse and survival, in contrast to both S100 and S100A1B.

The Role of Cystatin C and the Angiogenic Cytokines VEGF and bFGF in Patients with Esophageal Carcinoma

Angiogenesis is the formation of new blood vessels out of the existing vascular bed. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent circulating angiogenic factors, whereas cystatin C is one of the most important extracellular inhibitors of several cysteine proteinases. Because proteases degrade interstitial connective tissue and basement membranes during tumor growth and metastasis, an association between cystatin C and the angiogenic factors seems plausible. The primary aim of the present study was to investigate if such a correlation exists between these serum markers. The secondary aim was to determine the prognostic value of these circulating cytokines and cystatin C, collected prior to therapy, in patients with esophageal carcinoma.A total of 42 patients with esophageal carcinoma donated serum samples prior to therapy. VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p=0.04), whereas bFGF was not (p=0.08). VEGF was significantly correlated with cystatin C (p=0.027). Survival analysis showed that VEGF regarded as a continuous variable was associated with a significantly poorer survival in the univariate analysis (p=0.023); however, this was not found for bFGF (p=0.46). Neither of the angiogenic factors were associated with survival in the multivariate analysis. In the univariate analysis, cystatin c was correlated with survival (p=0.01), but this was not found in the multivariate analysis (p=0.28).In conclusion, VEGF was correlated with cystatin C, possible explanations being discussed in the present article. Results of the present study indicate that use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, appears limited.

Expression of EGFR and LRIG proteins in oesophageal carcinoma with emphasis on patient survival and cellular chemosensitivity.

Background. Leucine-rich and immunoglobulin-like domains 1-3 (LRIG1-3) proteins have been implicated in the regulation of EGFR signalling. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG1-3 in oesophageal carcinoma, as well as the correlation between their expression levels and the chemosensitivity of oesophageal carcinoma cell lines. Patients and methods. Tumours from 80 patients with oesophageal carcinoma were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Oesophageal carcinoma cell lines were investigated for their expression of EGFR and LRIG1, 2, and 3 by quantitative real time RT-PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay. Results and discussion: Based on a total score of intensity and expression rates, a trend towards survival difference was found for EGFR (p = 0.09) and LRIG2 (p = 0.18) whereas for LRIG1 and -3 there was no trend towards any association with survival. Correlation analysis revealed a correlation with the clinical expression of EGFR and LRIG3 (p = 0.0007). Significant correlations were found between LRIG1 expression levels and sensitivity to cisplatin (r = −0.74), docetaxel (r = −0.69), and vinorelbine (r = −0.82) in oesophageal carcinoma cell lines. EGFR and the LRIG proteins may be functionally involved in oesophageal carcinoma, but larger materials are needed to fully elucidate the clinical implication.

The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival

BackgroundLung cancer causes approximately one million deaths each year worldwide and protein p53 has been shown to be involved in the intricate processes regulating response to radiation and/or chemotherapeutic treatment. Consequently, since antibodies against p53 (anti-p53 antibodies) are associated with mutations within the p53 gene it seems likely that these antibodies could, hypothetically, be correlated with prognosis.MethodsSerum samples from patients with non-small cell lung cancer (NSCLC) admitted to the Department of Oncology, University Hospital, Uppsala, Sweden, during 1983–1996 were studied. Anti-p53 abs were measured using a sandwich ELISA (Dianova, Hamburg, Germany).ResultsThe present study included 84 patients with stage IIIA-IV (advanced NSCLC). At least three serum samples from each patient were collected and altogether 529 serum samples were analysed for the presence of anti-p53 antibodies. The median value of anti-p53 antibodies was 0.06 (range 0 – 139.8). Seventeen percent of investigated NSCLC first serum samples (n = 84) expressed elevated levels of anti-p53 antibodies. Anti-p53 antibodies were not correlated to tumour volume or platelets.Survival analysis showed that anti-p53 antibodies were not associated with survival as revealed by univariate analysis (p = 0.29). However, patients with adenocarcinoma had a significantly poorer survival if they expressed anti-p53 antibodies (p = 0.01), whereas this was not found for patients with squamous cell carcinoma (p = 0.13). In patients where the blood samples were collected during radiation therapy, a statistically significant correlation towards poorer survival was found (p = 0.05) when elevated anti-p53 antibodies levels were present. No correlations to survival were found for serum samples collected prior to radiation therapy, during chemotherapy, or during follow-up. When anti-p53 antibodies were measured continuously, no increase in median anti-p53 values was observed the closer the individual patient come to death.ConclusionThe result of the present retrospective study indicates that anti-p53 antibodies are not suitable for predictions concerning selection of patients with a more favourable outcome. Further prospective studies are, though, needed to fully elucidate this issue.

Social Behaviour in Work Absence

By making use of a large-scale randomized experiment, we test whether social behaviour is important for work absence due to illness. The individuals treated in the experiment were exposed to less monitoring of their eligibility to collect sickness insurance benefits, which sharply increased their non-monitored work absence. This exogenous variation is exploited in two complementary analyses. In both analyses, we find significant social-behaviour effects. Using detailed data, we conclude that the social-behaviour effects most likely stem from fairness concerns.

Abstract A42: Characterization of EGFR and leucine‐rich repeats and immunoglobulin‐like domain proteins (LRIG1–3) in esophageal carcinoma with emphasis on patient survival

Background: Esophageal carcinoma is the seventh most common cause of cancer‐related death in the Western world and the incidence is increasing. The signal transduction system of epidermal growth factor receptor (EGFR) is of major importance for tumor growth in several types of malignancies and EGFR‐targeted therapy has been shown to able to regulate tumor growth. Leucine‐rich repeats and immunoglobulin‐like domain protein 1 (LRIG1) is an endogenous negative regulator of EGFR signaling. The functions of LRIG2 and −3 are at present not known, however, it has been postulated that they might also be involved in the regulation of growth factor signaling and tumor growth. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG1–3 in esophageal carcinoma as well as the correlation between their expression levels and the chemosensitivity of esophageal carcinoma cell lines. Patients and Methods: A total of 86 patients diagnosed with esophageal carcinoma were included in the study and their tumors were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Further, a total of nine esophageal carcinoma cell lines were investigated for their expression of EGFR, LRIG1, −2 and −3 by quantitative RT‐PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay. Results: Survival analysis using Kaplan‐Meir analysis showed that the staining intensities of EGFR and LRIG2 were significantly associated with short survival (p=0.025 and p=0.03, respectively), whereas the extent of staining of LRIG1 was associated with long survival (p= 0.045). Chemosensitivity studies demonstrated a significant correlation between LRIG1 expression levels and sensitivity to cisplatin (r=−0.74), docetaxel (r=−0.69) and vinorelbine (r=−0.82) in the investigated esophageal carcinoma cell lines. Conclusion: In the present study, the expression of EGFR and LRIG2 correlated negatively, whereas LRIG1 correlated positively, with survival of the esophageal carcinoma patients. Furthermore, a correlation between LRIG1 expression and chemosensitivity was observed, indicating a possible role in chemoresistance. The functions of LRIG1 and −2 and their connection with EGFR warrants further investigation. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A42.