Biomedical subjects

Y Soini

Publications and source records attributed to Y Soini.

At least 55 records · Page 3Linked to original sources

PubMed2000

Atypical bronchopulmonary carcinoids show a tendency toward increased apoptotic and proliferative activity.

BACKGROUND: Bronchopulmonary carcinoid tumors can be divided into typical and atypical carcinoids according to their histologic and clinical features. Atypical carcinoids tend to have less predictable biologic behavior and are associated with a worse prognosis than typical carcinoids. The authors examined apoptosis and the expression of apoptosis regulating proteins Bcl-2, Bax, Bak, and Mcl-1 in 21 typical and 10 atypical bronchopulmonary carcinoid tumors. To find features distinguishing the growth of these types of tumors, the expression of p53 protein and the proliferation marker Ki-67 were also investigated. Finally, the parameters were compared with clinical follow-up data. METHODS: Thirty-one bronchopulmonary carcinoid tumors were examined by using in situ 3'-end labeling of DNA (TUNEL) for apoptosis and immunohistochemical staining methods for Bcl-2, Bax, Bak, Mcl-1, p53, and Ki-67 in formalin fixed, paraffin embedded tissue specimens. RESULTS: The apoptotic indices (AIs) were low in general (mean 0.18%), but higher AIs (> 0.5%) were observed significantly more often in atypical than in typical carcinoids (P < 0.008) in association with shortened survival (P < 0. 008). No relation between apoptosis and Bcl-2, Bax, Bak, or Mcl-1 expression was found. Expression of p53 protein was detected in only three atypical carcinoids, which also had significantly higher AIs than p53 negative tumors (P < 0.03). Proliferation rates measured by Ki-67 index were unusually low; the highest proliferation rates were observed in atypical carcinoids. There was a positive correlation between AI and Ki-67 indices (P < 0.01). CONCLUSIONS: This study suggests that the extent of apoptosis in bronchopulmonary carcinoid tumors is low. This, together with a low proliferation rate and an apparent absence of p53 mutation, enables a benign growth pattern. Some atypical carcinoids with enhanced apoptosis are associated with shortened survival, clearly deviating from typical carcinoids.

Apoptosis↗

PubMed2000

Manganese superoxide dismutase as a diagnostic marker for malignant pleural mesothelioma.

Although several immunohistochemical markers are available, differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura is difficult. We have found that the immunoreactivity of manganese superoxide dismutase (MnSOD), an important antioxidant enzyme, is high in mesothelioma compared to healthy pleural mesothelium. The aim of the present study was to investigate whether MnSOD can be used in the differential diagnosis of malignant mesothelioma and metastatic adenocarcinoma of the pleura. MnSOD expression was assessed by using immunohistochemistry in biopsies of malignant mesothelioma (n = 35) and metastatic adenocarcinoma of the pleura (n = 21). MnSOD immunoreactivity was assessed semiquantitatively with and without microwave pretreatment. Fifteen of the 35 malignant mesotheliomas showed moderate or strong MnSOD expression without and 23 with microwave pretreatment, the corresponding figures for metastatic adenocarcinoma of the pleura being 1 and 2 out of 21 (P = 0.002 and P < 0.001, respectively by Fisher's exact test). Only mesothelioma biopsies showed strong MnSOD reactivity, and it was never negative in mesothelioma, whereas one-third of the adenocarcinomas showed no MnSOD reactivity. In conclusion, MnSOD immunoreactivity can, combined with other markers, aid the differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma of the pleura.

Adenocarcinoma↗

PubMed2000

Prognostic factors in tongue cancer - relative importance of demographic, clinical and histopathological factors.

The incidence of and mortality from squamous cell carcinoma (SCC) of the tongue have increased during the recent decades in the Western world. Much effort has been made to predict tumour behaviour, but we still lack specific prognostic indicators. The aim of our study was to evaluate the relative importance of the known demographic, clinical and histological factors in a homogeneous population-based group of patients with SCC of the mobile tongue. The demographic and clinical factors were reviewed retrospectively from primary and tertiary care patient files. Histological prognostic factors were determined from pre-treatment biopsies. The TNM stage was found to be the most important prognostic factor. In particular, local spread outside the tongue rather than spread to regional lymph nodes was related to poor prognosis. Several demographic and histopathological factors were closely related to TNM stage. When the cases were divided into stage I-II carcinomas and stage III-IV carcinomas, it appeared that the patient's older age (> 65 years), a high malignancy score and an absence of overexpressed p53 protein were associated with a poorer prognosis in stage I-II carcinomas. Such cases may require more aggressive treatment. Among patients with stage III-IV carcinomas, heavy use of alcohol was significantly associated with a poor disease-specific survival time.

Adult↗

PubMed2000

Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma.

In this study we investigated the immunohistochemical expression of inducible nitric oxide synthase (iNOS) in a set of normal pleural mesothelial tissues, malignant mesotheliomas, mesothelioma cell lines and metastatic pleural adenocarcinomas. Furthermore, the expression of mRNA was assessed in four malignant mesothelioma cell lines in culture. Apoptosis and vascular density in malignant mesotheliomas was assessed by the TUNEL method and by immunohistochemistry with an antibody against FVIII-related antigen. Immunohistochemically mesothelial cells in non-neoplastic healthy pleural tissues were mostly negative for iNOS. Positivity for iNOS was observed in 28/38 (74%) and 24/25 (96%) of malignant mesotheliomas and metastatic pleural adenocarcinomas, respectively. Epithelial and mixed mesotheliomas expressed more often strong iNOS immunoreactivity compared to the sarcomatoid subtype (P = 0.023). Moreover, metastatic adenocarcinomas expressed more often iNOS positivity than mesotheliomas (P = 0.021). Experiments with the cell lines confirmed that malignant mesothelioma cells are capable of synthesizing iNOS. No significant association was found between iNOS expression and apoptosis or vascular density in malignant mesotheliomas. The higher expression of iNOS in the epithelial subtype of mesothelioma and pleural metastatic adenocarcinoma might be due to an increased sensitivity of these cell types to cytokine-mediated iNOS upregulation. The strong expression of iNOS suggests a putative role for NO in the growth and progression of these tumours.

Adenocarcinoma↗

PubMed2000

Increased amount of type III pN-collagen in human abdominal aortic aneurysms: evidence for impaired type III collagen fibrillogenesis.

PURPOSE: This study aimed to characterize the distribution of structural domains of type I and III collagens in the wall of abdominal aortic aneurysms (AAAs), by the use of undilated atherosclerotic aortas (aortoiliac occlusive disease [AOD]) and healthy abdominal aortas as controls. METHODS: Immunohistochemical staining was applied with antibodies for the aminoterminal propeptides of type I (PINP) and type III (PIIINP) procollagens, which represent newly synthesized type I and III pN-collagens. In addition, an antibody against the aminoterminal telopeptide of type III collagen (IIINTP) was used as a means of detecting maturely cross-linked type III collagen fibrils. RESULTS: The newly synthesized type III procollagen detected by means of PIIINP staining was concentrated in the media in aneurysmal aortas, whereas type I pN-collagen was localized in the intima in both AAAs and AODs. The healthy aortas showed no immunoreactivity for either PIIINP or PINP. The cross-linked type III collagen, detected by means of IIINTP staining, stained transmurally in all study groups, but appeared more abundant in the media in AAAs. CONCLUSION: Our results strongly suggest that the metabolism of type III collagen is enhanced in AAAs. Intensive type III pN-collagen staining was present mainly in the media layer in AAAs, suggesting a role of type III collagen in aneurysm formation, whereas type I pN-collagen was present in the intima in both AAAs and AODs, suggesting that type I collagen synthesis is a fibroproliferative response related to the atherosclerotic process. The increased type III pN-collagen in AAAs may result in impaired fibril formation and, thus, in decreased tensile strength of aneurysmal tissue.

Aged↗

PubMed2000

Localization of MT1-MMP, TIMP-1, TIMP-2, and TIMP-3 messenger RNA in normal, hyperplastic, and neoplastic endometrium. Enhanced expression by endometrial adenocarcinomas is associated with low differentiation.

We studied membrane-type matrix metalloproteinase-1 (MT1-MMP), tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, and TIMP-3 messenger RNA (mRNA) using in situ hybridization to elucidate their temporal and spatial expression patterns in normal, hyperplastic, and neoplastic endometrium. All mRNAs studied were expressed weakly in proliferating endometrium but were induced strongly in late secretory endometrium except MT1-MMP. Endometrial hyperplasia samples did not show increased MT1-MMP or TIMP mRNA expression, indicating that the overall expression patterns in hyperplasia are comparable to those in proliferating endometrium under estrogen effect and that synthesis of extracellular matrix proteins, rather than degradation, predominates in this condition. Exceptionally, stromal cells in areas of desquamation were seen to express focally intense MT1-MMP mRNA in hyperplasia samples. All mRNAs investigated were expressed increasingly in endometrial adenocarcinomas, especially in less differentiated carcinomas. Furthermore, gelatin zymography revealed higher functional degradative activities in carcinoma tissues than in normal endometrium. Our results indicate that MT1-MMP expression, together with that of TIMPs, is involved most notably in normal endometrium under progesterone effect and, without being connected to cyclic hormonal levels, has an important role in the invasive growth of endometrial adenocarcinomas.

Adenocarcinoma↗

PubMed2000

Tenascin mRNA expression at the foci of recent injury in usual interstitial pneumonia.

To elucidate which cells are synthesizing tenascin in usual interstitial pneumonia (UIP) we have analyzed thoracoscopic or open lung biopsies from 30 patients with UIP by mRNA in situ hybridization, using (35)S-labeled tenascin RNA probes. The phenotype of the cells expressing tenascin mRNA was confirmed by immunohistochemical stainings of serial sections with antibodies against alpha-smooth muscle actin and human cytokeratin. The results demonstrate that tenascin is expressed at the foci of recent lesions consisting of intralumenal or incorporating loose fibrotic buds. The cells expressing tenascin mRNA were located in and underneath the newly formed epithelium. Immunohistochemical stainings showed that the cells in the newly formed epithelium were strongly cytokeratin positive, and thus evidently regenerating type 2 pneumocytes, while the cells underneath the newly formed epithelium were alpha-smooth muscle actin positive and apparently myofibroblasts. Tenascin mRNA expression was clearly stronger and more frequent in myofibroblasts than in type 2 pneumocytes, however. Weak tenascin mRNA expression was also found in metaplastic bronchiolar-type epithelium and alveolar macrophages. Our results are thus in good agreement with the previous studies showing that tenascin is actively synthesized at the early fibrotic lesions in UIP. Furthermore, results demonstrate that the interaction between the epithelium and the underlying connective tissue plays a significant role in tenascin synthesis and that myofibroblasts are mainly responsible for its synthesis in fibroblastic foci of UIP.

Adult↗

PubMed2000

Tenascin expression and distribution in pleural inflammatory and fibrotic diseases.

We hypothesized that tenascin expression is increased in pleural inflammatory and fibrotic diseases and that its expression can be used as a marker of active pleural involvement. For this purpose we analyzed 71 histological samples of inflammatory and fibrotic pleura from patients with asbestos-induced pleural reaction (n = 6), postcardiac injury syndrome (n = 6), parapneumonic infection and/or empyema (n = 23), tuberculosis (n = 5, rheumatoid disease (n = 1), and fibrosis with inflammation of unknown etiology (n = 30). All 71 cases were studied by immunohistochemistry for tenascin. In 19 selected cases tenascin mRNA in situ hybridization was also performed. In every case, tenascin was increased by immunohistochemistry. Most prominent immunoreactivity was detected in areas of newly formed fibrosis. Increased tenascin mRNA expression by in situ hybridization was detected in the individual cells of the newly formed fibrosis underneath the fibrinous exudate. The tenascin mRNA-positive cells localized in areas in which by immunohistochemical studies the cells were positive for alpha-smooth muscle actin, desmin, and vimentin, suggesting a myofibroblast phenotype. Tenascin mRNA expression was also seen less frequently in areas in which some cells were positive for cytokeratin. These cells might represent mesothelial cells entrapped in the inflammatory lesion. Alternatively, they might represent fibroblast-type cells with aberrant cytokeratin expression. We conclude that in pleural inflammatory and fibrotic diseases tenascin immunoreactivity is increased and tenascin mRNA-positive cells localized mainly in the areas of myofibroblast- and, less often, mesothelial-type cells, suggesting that mainly myofibroblasts and, less commonly, also mesothelial cells might be responsible for tenascin expression in pleural inflammatory and fibrotic diseases. (J Histochem Cytochem 48:1257-1268, 2000)

Aged↗

PubMed2000

Apoptosis in gallbladder carcinomas and dysplasias, its relation to the expression of caspases 3, 6 and 8 and apoptosis regulating proteins bcl-2, mcl-1 and bax.

In this study we investigated apoptosis and the expression of caspases 3, 6 and 8 and bcl-2, mcl-1 and bax in 39 gallbladder carcinomas and 7 epithelial dysplasias. The average apoptotic index was 0.68 +/- 0.91%. The extent of apoptosis was higher in grade II-III than grade I tumours or epithelial dysplasias (p = 0.003). Also, tumours invading beyond serosa or into other organs (T3-T4) had a higher apoptotic index than other tumours (p = 0.05). Caspase 3 expression was found in 37 (95%) and caspase 6 and 8 expression each in 30 (77%) carcinomas. Their expression associated with each other and tended to increase along with the progression of the lesions. Bcl-2 expression was found in only 4 (10%) tumours. In contrast, mcl-1 positivity was found in 34 (87%) and bax positivity in all cases. The results show that apoptosis is increased along with progression of the neoplastic lesions of the gallbladder epithelium. Caspases 3, 6 and 8 are strongly expressed in gallbladder carcinomas suggesting that they contribute to the increased apoptosis observed in them. Of the bcl-2 family proteins, bcl-2 was expressed infrequently suggesting that it does not play any significant role in apoptosis inhibition in gallbladder tumours.

Caspase 3↗

PubMed2000

eNOS expression is associated with the estrogen and progesterone receptor status in invasive breast carcinoma.

In this study we investigated the immunohistochemical expression of eNOS and nNOS in 80 invasive breast carcinomas. Since NO is known to influence apoptosis and angiogenesis we also determined the apoptotic index of the tumor cells by the TUNEL method and tumor angiogenesis by immunostaining the sections with FVIII-related antigen and assessing the number of positively stained vessels. Respectively, 65% and 11% of the cases expressed cytoplasmic positivity for eNOS and nNOS. The mean apoptotic index of the tumors was 0.60%. eNOS or nNOS expression did not associate with the apoptotic index (p=0.36 and p=0.58, respectively). Cases with a positive estrogen or progesterone receptor status were significantly more often eNOS positive than receptor negative cases (p=0.012 and p=0.015, respectively). No association was found between the estrogen or progesterone receptor status and nNOS expression. Neither eNOS nor nNOS expression was associated with vascular density, tumor grade or the TNM status of the tumors. The results show that eNOS and nNOS are expressed in breast carcinomas possibly contributing to their NO synthesis. No association with apoptosis or angiogenesis was detected. eNOS expression was, however, associated with the positive estrogen and progesterone receptors status suggesting that its synthesis might be regulated by hormonal stimulation.

Apoptosis↗

PubMed2000

A high number of tumor-infiltrating lymphocytes are associated with a small tumor size, low tumor stage, and a favorable prognosis in operated small cell lung carcinoma.

Tumor-infiltrating lymphocytes, apoptosis, and angiogenesis have a pivotal role in tumor growth control. This study was undertaken to analyze the associations of these factors and their role in the prognosis, defined as survival time, of 56 patients operated on for small cell lung carcinoma (SCLC). Immunohistochemically detected T cells and macrophages were the most abundant tumor-infiltrating lymphocytes in SCLC, whereas the number of B cells was small. There was a trend in the number of intratumoral cytotoxic/suppressor CD8 cells that were associated with the extent of apoptotic bodies in SCLC, as measured by in situ 3'-end labeling of apoptotic DNA. A high number of intratumoral T cells and CD8 cells were associated significantly with a low tumor size (<3 cm) and low tumor stage (stages I-II). A high number of intratumoral macrophages were associated with a low tumor stage and angiogenesis, as measured by microvessel density. A high number of T cells, CD8 cells, and macrophages and a low tumor size (<3 cm) were prognostic markers predicting favorable survival time of the patients with SCLC.

Adult↗

PubMed2000

Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas.

In this investigation, we studied the expression of inducible nitric oxide synthase (iNOS) and its association to apoptosis and angiogenesis in 43 in situ and 68 invasive breast carcinomas. Its expression was studied immunohistochemically using a polyclonal iNOS antibody, and the staining was evaluated both in tumor and stromal cells. Apoptosis was detected by 3' end labeling of fragmented DNA (terminal deoxynucleotidyl transferase-mediated nick end labeling method). Vascularization was detected immunohistochemically using an antibody to the FVIII-related antigen, and calculated microvessel densities were determined. In addition to strong iNOS expression in stromal cells, iNOS positivity was observed in tumor cells in 46.5% of in situ and 58.8% of invasive carcinomas. In invasive carcinomas, there were more cases with iNOS positivity both in tumor and stromal cells compared to in situ carcinomas (0.007). The proportion of cases with iNOS-positive tumor cells increased in in situ carcinomas from grade I to III (20.0%, 46.2%, and 73.3%). In invasive ductal carcinomas, there were more cases with iNOS-positive tumor cells than with in situ carcinomas (P = 0.04). Carcinomas with both iNOS-positive tumor and stromal cells had a higher apoptotic index (P = 0.02) and a higher calculated microvessel densities index (P = 0.02). A high number of iNOS-positive stromal cells associated with metastatic disease (P = 0.05). The results show that breast carcinoma cells, in addition to stromal cells, express iNOS and are capable of producing NO. Carcinomas with iNOS-positive tumor and stromal cells have a higher apoptotic indices and increased vascularization, suggesting that iNOS contributes to promotion of apoptosis and angiogenesis in breast carcinoma. The association of the number of iNOS-positive stromal cells with metastatic disease might be attributable to stimulation of angiogenesis, resulting in a higher vascular density and consequently a higher probability for tumor cells to invade.

Adenocarcinoma, Mucinous↗

PubMed2000

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in hepatocellular and pancreatic adenocarcinoma: implications for tumor progression and clinical prognosis.

In the present study, we used in situ hybridization to study 36 primary hepatocellular carcinomas (HCCs) and 35 pancreatic adenocarcinomas to analyze the expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP-9 mRNAs. In HCCs, MT1-MMP mRNA was mainly expressed by cancer cells and to a lesser extent by stromal cells. MMP-2 mRNA was expressed predominantly by cells of tumor stroma, whereas MMP-9 mRNA was seen mainly in neoplastic epithelial cells. In pancreatic adenocarcinomas, MT1-MMP and MMP-9 mRNA were seen at moderate levels both in cancer and in stromal cells, whereas MMP-2 mRNA was predominantly expressed by the tumor stroma. Antigens of MMP-2, MMP-9, and MT1-MMP immunolocalized to the neoplastic epithelium and to the stromal cells in both tumor types. In gelatin zymography, increased amounts of latent and active MMP-2 were found in tumor samples of HCC as compared with adjacent nontumorous liver tissue. On the other hand, the latent form of MMP-9 was found in almost equal amounts both in tumor and normal liver samples, but its active form was present only in HCC. Expression of MT1-MMP mRNA had a tendency to be associated with a lower degree of differentiation in HCC, but such association was not noticed in pancreatic tumors. Correlation to the clinical data showed that MT1-MMP expression had a strong statistical association with a poor outcome of patients (P < 0.01). A similar tendency was also observed in pancreatic adenocarcinomas, but the association did not reach statistical significance. MMP-2 and MMP-9 mRNA expression did not have significant correlation with prognosis. The results of this study support the previous suggestions of the importance of MT1-MMP for malignant growth and indicate that increased MT1-MMP mRNA expression by tumor cells in HCCs and pancreatic adenocarcinomas may have prognostic significance.

Adenocarcinoma↗

PubMed1999

Germ-line TP53 mutations in Finnish cancer families exhibiting features of the Li-Fraumeni syndrome and negative for BRCA1 and BRCA2.

Mutations in BRCA1 and BRCA2 account for a large portion of the inherited predisposition to breast and ovarian cancer. It was recently discovered that mutations in these two genes are less common in the Finnish population than expected. Because the genetic background of breast cancer, in particular, is largely obscure, it became necessary to search for mutations in other susceptibility genes. Because seven of our BRCA1 and BRCA2 mutation-negative families fulfilled the criteria of either Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL), we decided to screen them for germ-line TP53 mutations in exons 5-8 using a dual-temperature single-strand conformation polymorphism assay (SSCP). Two missense mutations (Asn235Ser and Tyr220Cys) were identified. The clinical significance of these findings was evaluated by comparison to previously reported germ-line TP53 mutation data, and by using the tumor loss of heterozygosity (LOH) analysis. In addition, an immunohistochemical analysis of tumor specimens from mutation-positive individuals was performed. Our results suggest that the observed missense mutations confer susceptibility to cancer, and that germ-line TP53 mutations would therefore explain an additional fraction of hereditary breast cancer in Finland.

BRCA2 Protein↗

PubMed1999

Expression of the laminin gamma2 chain in different histological types of lung carcinoma. A study by immunohistochemistry and in situ hybridization.

Sixty-four malignant lung tumours and 12 of their regional lymph node metastases were analysed for expression of the laminin gamma2 chain by immunohistochemistry and in situ hybridization. Expression of the laminin gamma2 chain was strongest in squamous cell carcinomas, followed by adenocarcinomas and large cell carcinomas. Positive cells, except for large cell carcinomas, were located at the epithelial-stromal interface of tumour clusters. An important exception was small cell lung carcinoma, with only a low level of laminin gamma2 chain expression. Apart from tumour type, this may reflect the relatively scanty fibrous stroma in these tumours and supports previous observations that small cell lung carcinoma cells, contrary to other types, lack surface expression of alpha(6)beta(4) integrin, the specific laminin-5 binding receptor. In frozen sections, immunohistochemistry showed linear basement membranes around tumour clusters in squamous cell carcinomas and adenocarcinomas. This shows that carcinoma cells are capable of heavy deposition of the laminin gamma2 chain around tumour clusters and suggests that a laminin gamma2 chain-containing substrate may be of significance for the spread and growth of malignant tumours.

Adenocarcinoma↗

PubMed1999

Apoptotic activity is increased in the newly formed fibromyxoid connective tissue in bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP) are clinically and histologically distinguishable interstitial lung diseases both sharing the presence of the newly formed fibromyxoid connective tissue as a histologic feature. In BOOP the newly formed connective tissue is susceptible to even complete reversal, but in UIP it participates in the remodeling of the pulmonary tissue. In this study we have tested the hypothesis that the apoptotic activity in the fibromyxoid lesions is higher in BOOP than in UIP. Apoptotic activity in cells of the newly formed connective tissue in BOOP and UIP was visualized by TUNEL. Apoptosis-regulating proteins bcl-2, mcl-1, and bax were visualized by immunohistochemistry. The number of the apoptotic events was given as an apoptotic index giving the percentage of the apoptotic cells and bodies of the total cell number. Our results show that the apoptotic activity is clearly higher in the fibromyxoid lesions of BOOP (mean, 0.7; S.D., +/-0.51) compared with those of UIP (mean, 0. 13; S.D., +/-0.14, p < 0.003). The results thus suggest that apoptosis has an important role in the resolution process of the newly formed connective tissue in BOOP. The low level of apoptosis in UIP could, on the other hand, suggest that a decreased apoptosis in cells of the fibromyxoid stroma might pathogenetically relate to a decreased resolution of these lesions in UIP. No significant difference was found in the expression of bcl-2, mcl-1, and bax in BOOP and in UIP, suggesting that regulation of apoptosis might partly bypass the influence of these proteins.

Apoptosis↗

PubMed1999

Intraluminal fibromyxoid lesions in bronchiolitis obliterans organizing pneumonia are highly capillarized.

Bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP; ie, cryptogenic fibrosing alveolitis of mural type, CFA) are clinically and histologically distinguishable interstitial lung diseases. Both contain intraluminal lesions of newly formed fibromyxoid connective tissue. In BOOP, the fibromyxoid lesions are susceptible to complete reversal, but in UIP they are supposed to participate in the remodeling of the interstitium. Our hypothesis was that capillarization of the intraluminal fibromyxoid lesions is more frequent in BOOP compared with UIP. In this study, we stained diagnostic thoracoscopic or open lung biopsy specimens of patients with BOOP (n = 9) and UIP (n = 10) with antibodies against human laminin, von Willebrand factor, and CD34 to reveal the microvasculature of intraluminal fibromyxoid lesions. Our results show that in BOOP there is abundant capillarization in the newly formed intraluminal fibromyxoid lesions often reminiscent of granulation tissue. The mean number of capillaries per area unit (mm2) was 107 +/- SD 74 in samples stained for laminin, 103 +/- SD 46 for von Willebrand factor, and 63 +/- SD 36 for CD34. In marked contrast, in UIP, the corresponding accounts were significantly lower, being 14 +/- SD 15 for laminin (P < .003), 11 +/- SD 14 for von Willebrand factor (P < .001) and 6 +/- SD 6 for CD34 (P < .001). The intraobserver (P < .001) and interobserver correlations (P < .002) were highly significant, showing that our results are reproducible. We conclude that the content and nature of the newly formed intraluminal connective tissue, for example, in the form of vascular growth factors, are different in BOOP and in UIP, and this partly leads to the different clinical course of these diseases.

Adult↗

PubMed1999

Tumour infiltrating lymphocytes in relation to tumour angiogenesis, apoptosis and prognosis in patients with large cell lung carcinoma.

Immune escape of tumour infiltrating lymphocytes (TILs), angiogenesis and apoptosis are important factors that contribute to tumour growth. In the present study immunohistochemical methods were used to investigate the relationships of these factors and their role in the prognosis of 38 patients operated on for a large cell lung carcinoma (LCLC). T cells and macrophages were most commonly found TILs in LCLC while the number of intratumoural B cells was small. A high number of intratumoural macrophages associated with angiogenesis, as measured by microvessel density (MD). TILs were not associated with the extent of apoptosis in LCLC, as measured by in situ 3'-end labelling of apoptotic DNA. The high number of intratumoural macrophages and B cells was a prognostic marker showing a better survival time of the patients with LCLC. Furthermore, a high number of intratumoural macrophages was significantly associated with longer disease free survival and low tumour stage of the patients with LCLC. A high number of intratumoural B cells and macrophages was associated with a small tumour size suggesting that both B cells and macrophages are important TILs limiting the growth of LCLC. Instead, T cells were not associated with survival or with the size or stage of the tumour suggesting that cytotoxic T cells are less important mediators of tumour host interaction in LCLC than B cells and macrophages.

Adult↗