Localizing and photosensitizing mechanism by tetra(3-hydroxyphenyl)porphin in vivo on human malignant melanoma xenografts in athymic nude mice

Observations on time-dependent localization of tetra(3-hydroxyphenyl)porphin (3-THPP) in human malignant melanoma transplanted to athymic nude mice from 1 to 120 h after intraperitoneal (i.p.) 10 mg kg^–1 b.w. administration were made by means of fluorescence microscopy. Fluorescence was found on the membrane of the melanoma cells and in the cytoplasm with a peak fluorescence intensity at 24 h post-injection of 3-THPP. The growth of the tumour cells was obviously inhibited at an early stage after PCT. Morphological changes of the tumour at various intervals after treatment by PCT with 3-THPP were also observed. Diffuse degeneration of the tumour cells with swelling of mitochondria and endoplasmic reticulum, heterochromatin aggregation and margination, etc., and subsequently diffuse necrosis with little or no the background of tumorous vascular response were found at an early stage after PCT. On the other hand, it was also observed that the necrosis of the melanoma areas was caused as a consequence of tumorous vascular injury at a later stage after PCT. Thus, two tumoricidal processes caused by PCT with 3-THPP were seen: a direct phototoxic action on tumour cells at an early stage after PCT and an indirect effect secondary to tumorous vascular injury at a later period after PCT.     

Histological findings in erosive prepyloric changes

To study the histology of erosive prepyloric changes (EPC), 5 bioptic specimens per examination were obtained from the prepyloric mucosa during 161 upper endoscopies in persons with and without EPC. The macroscopic erosions of EPC grade 3 were histologically verified in 88% of the cases. Histologically diagnosed erosions were always accompanied by an element of acute inflammation. The incidence of acute inflammation increased with increasing grades of EPC, from 5% in grade 0 and 1, through 26% in grade 2, to 96% in grade 3. The incidence of chronic inflammation was 0 in grade 0, 50% in grade 1, 46% in grade 2, and 90% in grade 3. On the whole, gastritis was found in 98% of the cases with EPC grade 3, as compared with approximately 50% in grades 2 and 1. Fibrosis was diagnosed in all the cases. The mean thickness of the foveolar layer increased with increasing grades of EPC, the values being significantly higher in grades 2 and 3 than in grade 0, with, however, considerable overlapping between groups. Cimetidine was found to have no effect on the histological features of chronic/acute inflammation and erosion.     

Expression of bcl-6 and CD10 protein is associated with longer overall survival and time to treatment failure in follicular lymphoma

Follicular lymphomas (FLs) are a heterogeneous group of tumors, but prognostic factors are evaluated insufficiently in this common hematologic neoplasm. While bcl-6 and CD10 are expressed characteristically in FLs, their significance for biologic behavior of FL has not been studied previously. Samples from 73 patients with FL and clinical follow-up from 7 to 231 months were evaluated by immunohistochemical analysis. Patients with high levels of bcl-6 expression had favorable overall survival (OS) (P = .003), disease-specific survival (DSS) (P = .033), and time to treatment failure (P = .003) compared with patients with low levels of bcl-6 expression. Multivariate analysis showed that the results for OS, DSS, and time to treatment failure were independent of the international prognostic index. Patients with CD10+ FLs also had longer OS (P = .001), DSS (P = .007), and time to treatment failure (P = .004), and grade 1 FL was associated with better OS (P = .01) and a statistical trend for longer DSS (P = .05) and time to treatment failure (P = .05), but these results were not independent of bcl-6 expression or the international prognostic index in multivariate analysis.     

Pregnancy and breast cancer: a population-based study

The incidence of pregnancy-associated breast cancer, i.e. during pregnancy and lactation, and of pregnancy subsequent to a breast-cancer diagnosis will increase as more women choose childbearing at a later age. Few larger series are published on pregnancy-associated breast cancer. In a population-based study, we evaluated the outcome and prognostic factors in 173 breast-cancer patients. One hundred and twenty-two patients had pregnancy-associated breast cancer (20 coincident with pregnancy and 102 during lactation) and 51 patients had pregnancy subsequent to breast cancer. The median follow-up time was 151 months. Histopathological parameters and immunoreactivity for oestrogen and progesterone receptors c-erbB-2 and c-erbB-4 were studied. All three groups had tumours with high histological grade, low frequency of hormone receptors and high expression of c-erbB-2. The pregnancy and lactation groups were near identical with regard to all histopathological parameters and outcome. In the two pregnancy-associated breast-cancer groups, tumours were significantly larger, with more extensive lymph-node involvement. For node-negative tumours the respective 5- and 10-year survival rates were 62% and 50% in the pregnancy group and 60% and 50% in the lactation group. For node-positive tumours, respective 5- and 10-year survival rates were 50% and 34% in the pregnancy group and 50% and 33% in the lactation group. In the subsequent group, overall survival was high in both node-negative and -positive groups, with 5- and 10-year survival rates of 80% and 73% and 86% and 76%, respectively. Tumour size, lymph-node status, histological grade, progesterone receptor, oestrogen receptor and c-erbB-2 were significant prognostic factors in the pregnancy-associated breast-cancer patients.     

TP53 mutations in prostatic cancer. Analysis of pre- and post-treatment archival formalin-fixed tumour tissue

The TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin-fixed pre-and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resistant. Six of the 34 (18 per cent) therapy-responding tumours and 19 of the 50 (38 per cent) hormone-resistant tumours showed p53 protein accumulation in the post-treatment specimen. Both pre- and post-treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5–8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-treatment samples, mutations were detected in three of the six patients with hormone-responsive tumours and in 11 of the 19 patients with hormone-resistant tumours. The three (100 per cent) patients with therapy-responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy-resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post-treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations were poorly differentiated compared with tumours without mutation (P<0·04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a ‘hotspot’ for mutation in the progression of the disease.     

Expression of CD44 in effusions of patients diagnosed with serous ovarian carcinoma – diagnostic and prognostic implications

CD44 is a family of cell adhesion molecules involved in a variety of cellular functions. The present study analysed the expression of two CD44 isoforms in serous effusions of patients diagnosed with ovarian carcinoma and corresponding primary and metastatic lesions. Fifty-eight effusions, 23 primary ovarian tumours, and 44 metastatic lesions were studied for protein expression of CD44s and v3-10 using immunohistochemistry. Results were correlated with clinical parameters. CD44v3-10 was seen in carcinoma cells in the majority of cases at all sites. Malignant effusions showed an up-regulation of CD44s compared to both primary tumours and metastatic solid lesions. Mesothelial cells frequently expressed CD44s, but were rarely immunoreactive for v3-10. CD44s immunoreactivity in cancer cells in effusions was significantly more often observed in patients with FIGO stage 3 than in stage 4 patients (P = 0.045). Staining results did not correlate with age, effusion site, metastatic site, tumour grade or residual tumour mass after initial surgery. Likewise, comparison of overall and disease-free survival with expression of the CD44 isoforms studied did not reveal any statistically significant associations. The up-regulation in CD44 levels in effusions, primarily in stage 3 disease, suggests that adhesion of ovarian carcinoma cells to mesothelium may be regulated at the level of CD44s expression, and provides further evidence of phenotypic alteration in the transition from primary tumour cell clones to effusions. The similar expression profile of CD44 in carcinoma cells in peritoneal and pleural effusions supports our previous observations and the hypothesis that carcinoma cells in peritoneal effusions are truly metastatic. This revised version was published online in July 2006 with corrections to the Cover Date.     

Type 1 protein tyrosine kinases in benign and malignant breast lesions

Aims : To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.  

Methods and results

Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.  

Conclusion

Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours.     

Solitary fibrous tumour of the thyroid: Clinicopathological,immunohistochemical and ultrastructural study of three cases

We describe three cases of solitary fibrous tumour (SFT) arising from thyroid stroma. Grossly, the tumours were clearly delimited but only partly encapsulated. The following histomorphological growth patterns were observed: bundles of cells in storiform configuration; non-structured bundles; prevalence of fibrous matrix; highly cellular, non-structured; prevalence of loose, non-structured extracellular substance; cellular proliferation and vascular spaces in a haemangiopericytic configuration and a lipomatous component. Immunohistochemical investigation demonstrated intense, diffuse vimentin positivity and focal, less intense actin positivity in all three cases. At electron microscopy we observed a primitive cell of mesenchymal type, with cytoplasm poor in organelles and rich in filaments; this cell sometimes presented differentiation characteristics. SFT is at present the most correct term for the lesions presented here despite some morphological characteristics which differ from cases reported in the literature.     

Hürthle cell and mitochondrion-rich papillary carcinomas of the thyroid gland: an ultrastructural and immunocytochemical study

Of 52 consecutive papillary carcinomas of the thyroid, the following cases were included in this study: one Hürthle cell papillary carcinoma, one papillary carcinoma with foci of Hürthle cells, and 10 cases of papillary carcinoma with abundant mitochondria (volumetric density of mitochondria greater than or equal to 20%). All cases were studied by light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and immunocytochemistry. Our results showed that papillary carcinomas mainly or exclusively composed of Hürthle cells are very rare; that Hürthle cell papillary carcinomas of the thyroid share the biologic characteristics and blend insidiously with the so-called mitochondrion-rich papillary carcinomas; that TEM and SEM can provide useful evidence for achieving the differential diagnosis between Hürthle cell and so-called mitochondrion-rich papillary carcinomas; and that immunocytochemical studies are useless in the aforementioned differential diagnosis.