Chondrosarcoma of the Chest Wall: A Single Institution Review of 50 Cases.

INTRODUCTION: Chondrosarcoma (CS) is most common primary osseous tumor of the chest wall. The aim of this study was to report results from surgical procedures and evaluate clinical factors predicting survival of patients with chest wall CSs treated in a single tertiary sarcoma center. MATERIALS AND METHODS: Fifty patients with primary CS located in the ribs and sternum were included. Details of the clinical data and oncological outcomes, including local recurrence (LR) and disease-specific survival (DSS), were collected. RESULTS: The tumor was primarily originated in the sternum in 6 patients (12.5%) and in ribs 2 to 11 in the remaining patients. Specimens were histologically graded 1 in 13 patients (26%), 2 in 28 (56%), 3 in 8 (16%), and 1 (2%) as mesenchymal grade 3 CS. R0 margins were obtained in all cases. Reconstruction was warranted in 47 (94%) cases. Local recurrence developed in 3 (6%) patients, and the median time to LR was 17 (range, 16-68) months. Eight (16%) patients developed metastasis. Increasing tumor volume was a statistically significant factor for reduction of DSS. CONCLUSIONS: Chondrosarcoma of the chest wall can be treated effectively with clear margins, resulting in lower LR rate and higher DSS than CS of the extremities and pelvis. Metastasis of the chest wall mostly occurs in high-grade tumors, and the locations of the metastases differ greatly from those observed in CS of the extremities and pelvis. Metastases are commonly extrapulmonary, indicating the need for postoperative follow-up with multiple imaging modalities to monitor recurrence and metastases.

Immunohistochemical Glucagon-like Peptide-1 Receptor Expression in Human Insulinomas.

Insulinomas are rare functional pancreatic neuroendocrine tumours, which metastasize in 10% of cases. As predicting the prognosis can be challenging, there is a need for the determination of clinicopathological factors associated with metastatic potential. The aim of this study is to evaluate the glucagon-like peptide-1 receptor (GLP-1R) expression in insulinomas and to analyse its association with clinicopathological features and patient outcome. This retrospective study involves pancreatic tumour tissue samples from fifty-two insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with a monoclonal GLP-1R antibody. Forty-eight of the forty-nine (98%) non-metastatic tumours expressed GLP-1R, while one non-metastatic, multiple endocrine neoplasia type 1 (MEN1)-related tumour and all three of the metastatic tumours lacked GLP-1R expression. The lack of GLP-1R expression was associated with impaired overall survival, larger tumour diameter, higher Ki-67 PI and weaker insulin staining. Somatostatin receptor 1-5 expression did not differ between GLP-1R-positive and GLP-1R-negative insulinomas. In conclusion, the lack of GLP-1R expression is associated with metastatic disease and impaired survival in insulinoma patients. Thus, GLP-1R expression could be a useful biomarker in estimating the metastatic potential of the tumour and the prognosis of surgically treated patients.

Single centre 30-year experience in treating retroperitoneal liposarcomas.

BACKGROUND AND OBJECTIVES: Liposarcomas form a diverse group of tumors that represent the majority of retroperitoneal soft tissue sarcomas. Radical excision of these retroperitoneal liposarcomas is often challenging due to their large size and proximity to visceral organs and major vessels. Here we present the 30-year experience of our multidisciplinary sarcoma team in the treatment of these tumors and analysis of factors influencing survival. METHODS: Patients with retroperitoneal liposarcomas treated in Helsinki University Hospital from 1987 to 2017 were reviewed. Local recurrence-free survival, metastases-free survival, and disease-specific survival were assessed with Kaplan-Meier analysis, and factors influencing survival were evaluated with Cox regression. RESULTS: A total of 107 patients were identified. The median follow-up time was 5.4 years (interquartile range: 2.2-8.8 years). Local recurrence developed in 72% and metastases in 15% during follow-up. The 5-year disease-free survival was 31% and disease-specific survival was 66%. The multifactorial analysis revealed histological type and grade as predictors of disease-specific survival (P < .01) while multifocality carried a poor prognosis for local recurrence (P = .02) and higher histological grade for metastases (P < .01). CONCLUSIONS: Retroperitoneal liposarcomas rarely metastasize but tend to recur locally. For tumors that have been resected with macroscopically clear margins, histological, type, and grade are significant predictors of survival.

Estrogen receptor beta expression correlates with proliferation in desmoid tumors.

BACKGROUND AND OBJECTIVES: Estrogen receptor signaling and cyclin D1 have a major role in tumor cell proliferation in breast cancer. Desmoid tumors are rare neoplasms that may respond to endocrine treatment. The present study aimed to investigate the expression levels and the clinical relevance of estrogen receptor beta (ERß) and cyclin D1 in desmoid tumors. METHODS: This study consists of 83 patients with a surgically treated desmoid tumor. ERß and cyclin D1 expression was examined by immunohistochemistry in tissue microarrays. Cyclin A and Ki67 were studied in our previous work. RESULTS: Median ERß expression was 10.8%. ERß expression correlated with expression of the proliferation antigens Ki67 (rp = 0.35, P = 0.003), cyclin D1 (rp = 0.34, P = 0.004), and cyclin A (rp = 0.34, P = 0.004). ERß immunoexpression showed a trend towards predictive impact for recurrence as a continuous variable. Further explorative analysis indicated that very high ERß expression was related to high risk of relapse (hazard ratio [HR] 2.6; P = 0.02). Median cyclin D1 expression was 15.6%. High cyclin D1 expression was associated with high Ki67 and cyclin A expression. Cyclin D1 was not associated with time to recurrence. CONCLUSIONS: ERß and cyclin D1 immunopositivity correlated with high proliferation in desmoid tumors. High ERß expression might be predictive for postoperative recurrence.

High cyclin A expression, but not Ki67, is associated with early recurrence in desmoid tumors.

BACKGROUND AND OBJECTIVES: Desmoid tumors are soft-tissue tumors originating from myofibroblasts with a tendency to recur after surgery. High expression of proliferation markers is associated with shortened progression-free and/or overall survival in many neoplasms, including soft-tissue sarcomas. We investigated the prognostic role of cyclin A and Ki67 in desmoid tumors by immunohistochemistry. METHODS: The study included 76 patients with desmoid tumor operated at Helsinki University Hospital between 1987 and 2011. A tissue micro array (TMA) was constructed and the TMA sections were immunostained with cyclin A and Ki67 antibodies. A computer-assisted image analysis was performed. RESULTS: Cyclin A expression was evaluable in 74 and Ki67 in 70 patients. Cyclin A immunopositivity varied from 0% to 9.9%, with a mean of 1.9%. Cyclin A expression correlated significantly with Ki67. Cyclin A expression was associated with recurrence-free survival (HR 1.9, 95% CI = 1.1-3.2, P = .02), as were positive margin (HR 6.0, 95% CI = 1.6-22.5, P = .008) and extremity location (HR 5.3, 95% CI = 1.7-16.8, P = 0.005). Ki67 immunopositivity varied from 0.33% to 13.8%, with a mean of 4.6%, but had no significant prognostic impact (HR 1.1, P = .2). CONCLUSIONS: Our study indicates that cyclin A may be a new prognostic biomarker in surgically treated desmoid tumors.

Radiotherapy in desmoid tumors : Treatment response, local control, and analysis of local failures.

BACKGROUND: Desmoid tumors (aggressive fibromatosis) are rare soft tissue tumors which frequently recur after surgery. Desmoid tumors arise from musculoaponeurotic tissue in the extremities, head and neck, abdominal wall, or intra-abdominally. Our aim was to examine the outcome of radiotherapy of desmoid tumors in a single institution series. PATIENTS AND METHODS: We evaluated 41 patients with desmoid tumors treated with 49 radiotherapies between 1987 and 2012. Radiologic images for response evaluation were reassessed and responses to treatment registered according to RECIST criteria 1.1. For patients with local failures radiation dose distribution was determined in each local failure volume using image co-registration. Recurrences were classified as in-target, marginal, or out-of-target. Prognostic factors for radiotherapy treatment failure were evaluated. RESULTS: Radiotherapy doses varied from 20-63 Gy (median 50 Gy) with a median fraction size of 2 Gy. The objective response rate to definitive radiotherapy was 55% (12/22 patients). Median time to response was 14 months. A statistically significant dose-response relation for definitive and postoperative radiotherapy was observed both in univariate (p-value 0.002) and in multivariate analysis (p-value 0.02) adjusted for potential confounding factors. Surgery before radiotherapy or surgical margin had no significant effect on time to progression. Nine of 11 (82%) local failures were classified as marginal and two of 11 (18%) in-target. None of the recurrences occurred totally out-of-target. CONCLUSIONS: Radiotherapy is a valuable option for treating desmoid tumors. Radiotherapy dose appears to be significantly associated to local control.

Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by irreversible airflow limitation. Cigarette smoking represents the main risk factor, but the specific mechanisms of COPD are not completely understood. Our aim was to identify COPD-specific proteomic changes involved in disease onset and severity. A comparative proteomic analysis of 51 lung tissues from nonsmokers, smokers, smokers with mild to moderate (stage I-II) COPD, severe to very severe COPD (stage III-IV), and patients with α-1-antitrypsin deficiency (AATD) and idiopathic pulmonary fibrosis (IPF) was performed by cysteine-specific two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Selected COPD-specific changes were validated by immunoblotting and further by ELISA in 120 induced sputum and plasma samples from nonsmokers, smokers, and patients with COPD (stage I-III). Altogether 82 altered proteins were identified comprising COPD-, AATD-, and IPF-specific, overlapping, and unspecific changes. Cathepsin D (CTSD), dihydropyrimidinase-related protein 2 (DPYSL2), transglutaminase 2 (TGM2), and tripeptidyl-peptidase 1 (TPP1) were validated as COPD-specific. TGM2 was not associated with smoking and correlated with COPD severity in lung tissue. TGM2 levels in sputum and plasma were elevated in patients with COPD (stage II-III) and correlated with lung function. In conclusion, new proteins related to COPD onset and severity could be identified with TGM2 being a novel potential diagnostic and therapeutic target for COPD. Further studies in carefully characterized cohorts are required to validate the identified changes.

Overexpression of activin-A and -B in malignant mesothelioma - attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth.

Activin-A and activin-B, members of the TGF-ß superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cells in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth.

Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing.

BACKGROUND: Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM. METHODS: Exome sequencing was performed on DNA from 47 tumor tissues of MM (21) and LAC (26) patients, 27 of whom had been asbestos-exposed (18 MM, 9 LAC). In addition, 9 normal lung/blood samples of LAC were sequenced. Novel mutations identified from exome data were validated by amplicon-based deep sequencing. Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM. RESULTS: In asbestos-exposed MM patients, previously non-described NF2 frameshift mutation (one) and BAP1 mutations (four) were detected. Exome data mining revealed some genes potentially associated with asbestos exposure, such as MRPL1 and SDK1. BAP1 and COPG1 mutations were seen exclusively in MM. Pathogenic KRAS mutations were common in LAC patients (42 %), both in non-exposed (n = 5) and exposed patients (n = 6). Pathogenic BRAF mutations were found in two LACs. CONCLUSION: BAP1 mutations occurred in asbestos-exposed MM. MRPL1, SDK1, SEMA5B, and INPP4A could possibly serve as candidate genes for alterations associated with asbestos exposure. KRAS mutations in LAC were not associated with asbestos exposure.

Driver gene mutations of non-small-cell lung cancer are rare in primary carcinoids of the lung: NGS study by ion Torrent.

Lung carcinoids are rare neuroendocrine tumors of the lung. Very little is known about the genetic background of these tumors. We applied Ion Torrent Ampliseq next-generation technology to study hotspot mutations of 22 lung cancer-related genes from typical and atypical lung carcinoid tumors. DNA isolated from 25 formalin-fixed, paraffin-embedded carcinoid tumors were amplified to prepare barcoded libraries covering 507 mutations included in 90 amplicons. The libraries were pooled, purified, enriched, and sequenced on ion personal genome machine. The sequences were aligned and checked for known and novel variations using Torrent Suite Software v.4.0.2. One out of 25 patients had mutations in the targeted regions sequenced. This patient had mutations in BRAF, SMAD4, PIK3CA, and KRAS. All these mutations were confirmed as somatic and are previously known mutations. In summary, mutations in genes commonly mutated in non-small-cell lung cancer are not common in lung carcinoids.

ALK fusion and its association with other driver gene mutations in Finnish non-small cell lung cancer patients.

Screening of anaplastic lymphoma tyrosine kinase (ALK) gene fusions in non-small cell lung cancer (NSCLC) patients enables the identification of the patients likely to benefit from ALK-targeted therapy. Our aim was to assess the prevalence of ALK fusion in Finnish NSCLC patients, which has not been reported earlier, and to study the presence of ALK fusion in relation to clinicopathological characteristics and other driver gene mutations. A total of 469 formalin-fixed paraffin-embedded tumor tissue specimens from Finnish NSCLC patients were screened for ALK fusion by immunohistochemistry (IHC). For confirmation of IHC results, fluorescence in situ hybridization (FISH) was conducted for 171 specimens. Next-generation sequencing was performed for all ALK-positive specimens to characterize the association of ALK fusion with mutations in targeted regions of 22 driver genes. Of the 469 tumors screened, 11 (2.3%) harbored an ALK fusion, including nine adenocarcinomas and two large cell carcinomas. The IHC results for all 11 ALK-positive and 160 random ALK-negative specimens were confirmed by FISH. ALK fusion was significantly associated with never/ex-light smoking history (P<0.001) and younger age (P=0.004). Seven ALK-positive tumors showed additional mutations; three in MET, one in MET and CTNNB1, two in TP53, and one in PIK3CA. Our results show that ALK fusion is an infrequent alteration in Finnish NSCLC patients. Although the majority of ALK-positive cases were adenocarcinomas, the fusion was also seen in large cell carcinomas. Further studies are needed to elucidate the clinical significance of the coexistence of ALK fusion with MET, TP53, CTNNB1, and PIK3CA mutations.

Upregulation of activin-B and follistatin in pulmonary fibrosis - a translational study using human biopsies and a specific inhibitor in mouse fibrosis models.

BACKGROUND: Activins are members of the TGF-ß superfamily of growth factors. First, we identified by expression array screening that activin-B and follistatin are upregulated in human idiopathic pulmonary fibrosis (IPF). Next, we wanted to clarify their specific role in lung fibrosis formation. METHODS: We used specific antibodies for activin-A and -B subunits and follistatin to measure and localize their levels in idiopathic pulmonary fibrosis and control lung biopsies. To inhibit activin signaling, we used soluble activin type IIB receptor fused to the Fc portion of human IgG1 (sActRIIB-Fc) in two different mouse models of pulmonary fibrosis. RESULTS: Activin-B and follistatin mRNA levels were elevated in the human IPF lung. Immunoreactivity to activin-A, -B and follistatin localized predominantly to the hyperplastic, activated alveolar epithelium, but was also seen in inflammatory cells. Mice treated with sActRIIB-Fc showed increased skeletal muscle mass and a clear reduction in alveolar cell counts in bronchoalveolar lavage fluid, but no significant antifibrotic effect in the lung was observed. CONCLUSIONS: The upregulation of activin-B and follistatin in IPF is a novel finding. Our results indicate that activin inhibition is not an efficient tool for antifibrotic therapy, but could be useful in reducing alveolar cellular response to injury. Activin-B and follistatin levels may be useful as biomarkers of IPF.

Mutated ephrin receptor genes in non-small cell lung carcinoma and their occurrence with driver mutations-targeted resequencing study on formalin-fixed, paraffin-embedded tumor material of 81 patients.

Non-small cell lung carcinoma (NSCLC) is the most common subtype of lung cancer. The oncogenic potential of receptor tyrosine kinases (RTKs) is widely known and they are potential targets for tailored therapy. Ephrin receptors (Ephs) form the largest group of RTKs. Nevertheless, Ephs are not widely studied in NSCLC so far. The aim of our study was to investigate novel mutations of Eph genes (EPHA1-8, EPHB1-4, EPHB6) and their association with clinically relevant mutations in BRAF, EML4-ALK, EGFR, INSR, KDR, KRAS, MET, PDGFRA, PDGFRB, PIK3, PTEN, RET, and TP53 in NSCLC patients. Targeted resequencing was conducted on 81 formalin-fixed, paraffin-embedded NSCLC tumor specimens. We analyzed missense and nonsense mutations harbored in the coding regions of the selected genes. We found 18 novel mutations of Ephs in 20% (16 of 81) of the patients. Nearly half of these mutations occurred in the protein kinase domain. The mutations were not mutually exclusive with other clinically relevant mutations. Our study shows that Ephs are frequently mutated in NSCLC patients, and occur together with other known mutations relevant to the pathogenicity of NSCLC.

Comparison of targeted next-generation sequencing (NGS) and real-time PCR in the detection of EGFR, KRAS, and BRAF mutations on formalin-fixed, paraffin-embedded tumor material of non-small cell lung carcinoma-superiority of NGS.

The development of tyrosine kinase inhibitor treatments has made it important to test cancer patients for clinically significant gene mutations that influence the benefit of treatment. Targeted next-generation sequencing (NGS) provides a promising method for diagnostic purposes by enabling the simultaneous detection of multiple mutations in various genes in a single test. The aim of our study was to screen EGFR, KRAS, and BRAF mutations by targeted NGS and commonly used real-time polymerase chain reaction (PCR) methods to evaluate the feasibility of targeted NGS for the detection of the mutations. Furthermore, we aimed to identify potential novel mutations by targeted NGS. We analyzed formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens from 81 non-small cell lung carcinoma patients. We observed a significant concordance (from 96.3 to 100%) of the EGFR, KRAS, and BRAF mutation detection results between targeted NGS and real-time PCR. Moreover, targeted NGS revealed seven nonsynonymous single-nucleotide variations and one insertion-deletion variation in EGFR not detectable by the real-time PCR methods. The potential clinical significance of these variants requires elucidation in future studies. Our results support the use of targeted NGS in the screening of EGFR, KRAS, and BRAF mutations in FFPE tissue material.

Data-driven information retrieval in heterogeneous collections of transcriptomics data links SIM2s to malignant pleural mesothelioma.

MOTIVATION: Genome-wide measurement of transcript levels is an ubiquitous tool in biomedical research. As experimental data continues to be deposited in public databases, it is becoming important to develop search engines that enable the retrieval of relevant studies given a query study. While retrieval systems based on meta-data already exist, data-driven approaches that retrieve studies based on similarities in the expression data itself have a greater potential of uncovering novel biological insights. RESULTS: We propose an information retrieval method based on differential expression. Our method deals with arbitrary experimental designs and performs competitively with alternative approaches, while making the search results interpretable in terms of differential expression patterns. We show that our model yields meaningful connections between biological conditions from different studies. Finally, we validate a previously unknown connection between malignant pleural mesothelioma and SIM2s suggested by our method, via real-time polymerase chain reaction in an independent set of mesothelioma samples. AVAILABILITY: Supplementary data and source code are available from http://www.ebi.ac.uk/fg/research/rex.

Immunohistochemical somatostatin receptor expression in insulinomas.

Insulinomas are rare pancreatic neuroendocrine tumours. Most patients can be cured with surgery, but patients with a metastatic disease show impaired survival. The aim of this study was to evaluate somatostatin receptor (SSTR) 1-5 expression in insulinomas and to correlate the expression profile with clinicopathological variables and with patient outcome. This retrospective study involved 52 insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with monoclonal SSTR1-5 antibodies. All the 52 tumours (49 non-metastatic, 3 metastatic) expressed at least one SSTR subtype. SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%), SSTR5 (6%) and SSTR4 (0%). SSTR3 expression was associated with a larger tumour size (median diameter 19 mm vs. 13 mm, p = 0.043), and SSTR3 and SSTR5 expression were associated with impaired overall survival [HR 3.532 (95% CI 1.106-11,277), p = 0.033, and HR 6.805 (95% CI 1.364-33.955), p = 0.019 respectively]. Most insulinomas express SSTR2, which may be utilized in diagnostic imaging, and in planning individualized treatment strategies for insulinoma patients. Further studies are needed to clarify the association between SSTR profile and overall survival.

Case report and review: Angiosarcoma with thrombocytopenia after total hip arthroplasty.

Total hip arthroplasty (THA) is a common treatment for osteoarthritis and is also performed for other conditions, such as secondary arthritis due to developmental dysplasia of the hip. Various THA types may be complicated by osteolysis and an inflammatory pseudotumor due to an adverse reaction to metal debris. Rarely, THA has been associated with malignant tumors, but their causality remains unclear. In this case report, we describe a female patient with developmental dysplasia of the hip. She had undergone left metal-on-polyethylene THA, acetabular revision of the THA, and left total knee arthroplasty. In addition, she had a history of dyslipidemia and telangiectasia of the eyes, anemia, hiatal hernia, and pleuritis. A THA-associated mass (suspected to be a pseudotumor) had been detected during a previous hospital admission due to pleuritis. She was hospitalized due to swelling in her left lower limb, fatigue, and bruises. A clinical examination revealed anemia, thrombocytopenia, and growth of the suspected pseudotumor. Within 6 weeks, she presented with bleeding of the oral mucosa, hemoptysis, melena, severe thrombocytopenia that did not respond to treatment, elevated D-dimer and C-reactive protein levels, severe pain, increased osteolysis, and fractures around the THA. Infection or malignancy was suspected, but two trocar biopsies suggested an inflammatory pseudotumor. Since her anemia and thrombocytopenia were considered to have been caused by an inflammatory process within the suspected pseudotumor, her suspected pseudotumor and all THA components were surgically removed. However, she developed severe alveolar hemorrhaging and hypoxia and died 2 weeks after her surgery. Histopathological analysis of her surgical and autopsy samples revealed highly malignant angiosarcoma. Although individual cases of malignancies associated with THA have been reported, the literature lacks a clear association between THA and increased cancer risk. Most pseudotumors are non-malignant. The patient's case presented in this report exemplifies the challenges to the differential diagnosis of a THA-associated pseudotumor and rare angiosarcoma. Atypically rapid tumor growth, severe osteolysis, and deterioration in the general wellbeing suggest a malignant disease.

Sputum proteomics identifies elevated PIGR levels in smokers and mild-to-moderate COPD.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality around the world. However, the exact mechanisms leading to COPD and its progression are still poorly understood. In this study, induced sputum was analyzed by cysteine-specific two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry to identify proteins involved in COPD pathogenesis. The comparison of nonsmokers, smokers, and smokers with moderate COPD revealed 15 changed proteins with the majority, including polymeric immunoglobulin receptor (PIGR), being elevated in smokers and subjects with COPD. PIGR, which is involved in specific immune defense and inflammation, was further studied in sputum, lung tissue, and plasma by Western blot, immunohistochemistry/image analysis, and/or ELISA. Sputum PIGR was characterized as glycosylated secretory component (SC). Lung PIGR was significantly elevated in the bronchial and alveolar epithelium of smokers and further increased in the alveolar area in mild to moderate COPD. Plasma PIGR was elevated in smokers and smokers with COPD compared to nonsmokers with significant correlation to obstruction. In conclusion, new proteins in smoking-related chronic inflammation and COPD could be identified, with SC/PIGR being one of the most prominent not only in the lung but also in circulating blood.

Soft tissue sarcoma - a population-based, nationwide study with special emphasis on local control.

BACKGROUND: A prospective diagnostics and treatment protocol for extremity and trunk wall soft tissue sarcoma (STS) was introduced by the Scandinavian Sarcoma Group in 1986 and it was also widely adopted in Finland. We have updated the protocol and made it more detailed at the Helsinki University Central Hospital. We retrospectively compared diagnostics and treatment of STS in a nationwide population-based material to this protocol with special emphasis on local control. METHODS: Data for 219 patients with an STS of extremity or trunk wall diagnosed during 1998-2001 was retrieved from the nationwide Finnish Cancer Registry. Histologic review was performed. Treatment centres were divided into high-, intermediate- and low-volume centres based on the number of patients with final surgery during the study period. RESULTS: Significantly more patients were operated with a preoperative histological or cytological diagnosis at high-volume centres. No preoperative diagnosis was a strong predictor for the patient to undergo more than one operation (p < 0.0001). Wide surgical margin was achieved more often at high-volume centres, but in all centre categories a considerable percentage of patients with inadequate surgical margin did not receive adjuvant radiation therapy. Local control at five years was 82% at high-volume centres, 61% at intermediate-volume centres treating highest percentage of deep tumours and 69% at low-volume centres (p = 0.046). Local control improved as the number of patients operated (surgical volume of the centre) increased. CONCLUSION: The present quality-control study is the first nationwide population-based study to assess diagnostics and treatment of STS. When referred to a specialised sarcoma centre even patients with inadequate surgery can achieve good local control. STS is a rare cancer and its treatment should be centralised in Finland, which has 5.4 million inhabitants and approximately 100 new STSs of extremities and trunk wall annually.