Does lactoferrin behave as an immunohistochemical oncofetal marker in bone and cartilage human neoplasms?

By immunohistochemistry, lactoferrin (LF) has been extensively investigated in human neoplastic tissues; moreover, LF is able to promote bone growth in a murine model. Until now, no systematic studies on human osteocartilagineous fetal samples have been performed in comparison to corresponding neoplastic specimens to verify if LF may represent an oncofetal marker in this field of pathology. By a monoclonal antibody (clone 1A1; Biodesign International; w.d. 1:75) the distribution pattern of LF in bones of 25 human fetal tissues (8-34 gestation weeks), 10 adults (47-82 years) and 30 cartilage as well as 27 bone tumours (9-76 years) was analyzed. LF was encountered in 23/57 cases of osteocartilagineous tumors and namely in 10/10 giant cell tumours, 5/7 osteoid osteomas, 3/3 chondroblastomas, 3/3 chondromyxoid fibromas, 1/1 myeloma, 1/1 adamantinoma. No LF immunoexpression was detected in osteosarcomas, chondrosarcomas, ossifying fibromas, osteochondroma and enchondromas. In embryo-fetal tissues, LF immunoreactivity was localized in mesenchymal cells as well as in chondroblasts at the 8th gestational week and in immature osteocytes and osteoblasts up to the 18th gestation week, with a considerable decrease by the 24th week. No LF expression was found in any bone district since the 30th and up to the 34th week of gestation as well as in corresponding adult samples. Our findings indicate a role for LF as a bone growth regulator in the early phases of the human endochondral ossification, although the hypothesis of LF as oncofetal marker appears questionable in bone tumours.

[Acute abdomen for perforated gastrointestinal stromal tumor (GIST). A case report]. / Addome acuto da GIST perforato del digiuno. Contributo clinico.

The authors report on a case of voluminous perforated gastrointestinal stromal tumor (GIST) of small intestine and make a review to the light of most recent clinicopathologic advancements. The first clinical manifestation as acute abdomen due to their perforation extremely rare. Gastrointestinal stromal tumor (GIST) represent a rare group of multiform tumors with various biological behaviour. Were identified in the past as leiomyomas, leiomyosarcomas or leiomyoblastomas, has been reclassified on immunochemical features, with a positive expression of Kit (CD117 antigen). Traditionally the prognostic factors of these tumour are: mitotic rate, tumor size and anatomic site. The complete surgical resection and use of imatinib mesylate (Gleevec) are the best available approach.

Lactoferrin immuno-expression in human normal and neoplastic bone tissue.

Lactoferrin (Lf) expression was investigated by using a Lf monoclonal antibody in 50 formalin-fixed and paraffin-embedded human bone tumours [10 giant cell tumours (GCTs), 7 osteoid osteomas, 6 ossifying fibromas, 19 enchondromas, 2 chondroblastomas, 2 chondrosarcomas, 2 chondroblastic osteosarcomas, 1 myeloma and 1 adamantinoma] as well as in 8 samples of adult and foetal human normal bone specimens. In addition, the immunohistochemical expression of the estrogen receptor (ER), progesterone receptor (PR) and Ki-67 antigen was analysed on parallel sections from the same specimens. Quantification of Lf immunoreactivity was performed by using an Intensity Distribution (ID) score. Lf immuno-expression with a variable ID score was encountered in 19/50 tumours and specifically in 10/10 GCTs, in 5/7 osteoid osteomas, in 2/2 chondroblastomas as well as in the adamantinoma and in the myeloma. With reference to normal bone samples, Lf was expressed by the osteoblasts only in the foetal bone. No immunoreactivity for ER and PR was encountered in all neoplastic samples, and no correlation was found between Lf and sex steroid hormone receptor (ER and PR) immuno-expression. Even more, no association was evidenced between Lf immuno-reactivity and the growth fraction of the tumours, reflected by the Ki-67 labelling index. Lf expression in the osteoblastic lineage of bone-forming tumours, together with its presence in the osteoblasts of foetal bone, requires further investigations, although it cannot be ruled out that Lf might be involved in the bone formation in humans, similarly to what has been demonstrated in other species.

Endoglin (CD105) immuno-expression in human foetal and neonatal lungs.

Endoglin is a 180 KDa glycoprotein mainly expressed on endothelial cells of newly formed vessels. Its expression is increased by the hypoxia inducible factor 1 (HIF-1), a potent stimulator of VEGF expression. The relative hypoxic environment in which foetal lung develops favours HIF-1 dependent gene expression, including the endoglin and VEGF ones. Herein, we analysed endoglin immunoexpression in the human neonatal and foetal lung throughout gestation. Lungs from 18 foetuses (9-41 weeks), 7 preterm and 2 term infants were submitted to the immunohistochemical study. A slight immunostaining was found in some mesenchymal aggregates in the lungs of foetuses at the first trimester of pregnancy. At mid gestation, endoglin was evidenced in peri-tubular mesenchymal stem cells or in peri-canalicular vessels and in the endothelia of peri-bronchial vessels; by contrast, no immunoreaction was observed in case of Down syndrome or in a foetus with cardiac malformations. At late gestation and in preterm infants, endoglin antibody labelled endothelia of the alveolar capillaries and of peri-bronchial vessels. In case of alveolar capillary dysplasia (ACD) or macrosomy associated with maternal diabetes, endoglin expression was restricted to peri-bronchial vessels; no immunoreaction was encountered in foetuses with IUGR (intra-uterine growth restriction) or massive pulmonary haemorrhage. Lungs of term infants both displayed atelectasis; there was no evidence of endoglin immunoexpression in one case, whereby only the endothelia of peri-bronchial vessels were stained in the other. Our study suggests that lung vasculogenesis endures throughout gestation. Absence of endoglin staining in some pathologic conditions may reflect lung vasculogenesis disorders; nonetheless, since each pathologic state is represented by a single case in our cohort, further studies are required to clarify this issue.

Expression of NA/1 symporter (NIS) in endometrial mucosa of fertile, sterile and post-menopausal women.

The expression of the Na/I Symporter (NIS) in the basolateral cell membrane of the thyroid follicular cells is responsible for the active accumulation of iodide within the thyroid gland and for the subsequent biosynthesis of thyroid hormones. However, several tissues, such as salivary glands, breast, stomach, colon, ovary and endometrium, express NIS even if they are unable to organify iodide. In order to investigate a possible role of NIS in the endometrium, we analyzed, by immunochemistry, the expression of NIS in 44 endometrial samples of 20 patients with primary unexplained infertility, 14 fertile women and 10 in postmenopausal. NIS immunostaining was detected in endometrial cells belonging to the majority of sterile, post-menopausal and fertile women. However, the sterile and post-menopausal patients showed a higher percentage of NIS reactive cells compared to the fertile women (60+/-21% and 57+/-18% vs 19+/-9%; p=0.0001). NIS immunostaining was localized on the membrane and cytoplasm of the endometrial cells. We could not find any correlation between endometrial thickness and NIS immunoexpression. Our results indicate that, in the absence of histological markers, a sterile endometrium can be recognized because of the high expressions of NIS. Moreover, NIS expressions, elevated in both sterile and menopause women, is not related to the estrogen levels, but it could be modulated by factors common to the two conditions. In conclusion, we speculate that NIS may play a role in the development of female sterility.

Immunohistochemical evidence of caveolin-1 expression in the human fetal and neonatal striated muscle and absence in the adult's.

BACKGROUND: Caveolin-1 (Cav-1) is a 22-kd protein, which exerts essential roles in the regulation of cell proliferation and in transmembrane transport processes. It is mainly expressed in adipocytes, smooth muscle, fibroblasts, and endothelial cells. Its expression in striated muscle fibers is controversial. Indeed, most authors have attributed Cav-1 detection in striated muscle to endothelial cells, adipocytes, and fibroblasts secretion. Nonetheless, recent in vitro studies have shown that Cav-1 is expressed in L6 myoblasts and maintained during the differentiation process. In view of this, and, because only one study has heretofore explored Cav-1 expression in human striated muscle, the aim of the present study was to evaluate and to compare Cav-1 immunohistochemical expression in the human striated muscles of fetus, newborn, and adult. DESIGN: Samples of skeletal muscles of different sites and of myocardium were taken at autopsy from 13 fetuses and 4 newborns and submitted to the immunohistochemical analysis for Cav-1 together with 10 samples of adult skeletal muscle. RESULTS: Myocardial fibers displayed a weak immunoreaction in all samples, from both the newborns and the fetuses, independently of the week of gestation. Conversely, skeletal muscle fibers were only labeled in specimens from fetuses at late gestation and from the newborns, whereas no immunoreaction was evidenced in muscles taken from fetuses at mid-gestation and in the adult samples. CONCLUSIONS: This novel and unexpected pattern of Cav-1 expression in human skeletal muscle suggests a role for Cav-1 in terminal differentiation processes, which need to be clarified by further studies.

5-Lipoxygenase is coexpressed with Cox-2 in sporadic colorectal cancer: a correlation with advanced stage.

PURPOSE: It has been extensively documented that the cyclooxygenase inducible form and 15-lipoxygenase are implicated in colorectal carcinogenesis. Nonetheless, the role of other enzymes involved in the arachidonic acid metabolism, such as 5-lipoxygenase, in colorectal neoplasms has not been fully ascertained. This study was designed to evaluate 5-lipoxygenase expression in sporadic colorectal adenocarcinomas by using immunohistochemistry and to analyze its potential correlations with clinicopathologic parameters and with cyclooxygenase-2 expression. METHODS: Expression of 5-lipoxygenase and cyclooxygenase-2 were evaluated by immunohistochemistry in 50 surgically resected sporadic colorectal adenocarcinomas (28 male and 22 female patients age range, 47-88 (mean age, 69 +/- 8) years). The chi-squared and Spearman correlation tests were used to analyze correlations with clinicopathologic characteristics and to evaluate any relationships between expression of the two enzymes. P values <0.05 were considered statistically significant. RESULTS: 5-Lipooxygenase and cyclooxygenase-2 immunostaining was found in the cytoplasm of neoplastic cells in 41 (82 percent) and in 43 cases (86 percent), respectively. Spearman correlation test demonstrated a positive correlation in the expression of the two enzymes. A statistically significant correlation also was observed between 5-lipoxygenase expression and tumor stage and lymph node metastasis, whereas no significant correlations emerged regarding cyclooxygenase-2 expression and clinicopathologic parameters. CONCLUSIONS: Our study demonstrates that 5-lipoxygenase is expressed in colorectal adenocarcinomas in association with cyclooxygenase-2 expression. Moreover, an elevated expression of this enzyme seems to be significantly correlated with tumor aggressiveness. Further studies would clarify the need for target therapies inhibiting both metabolic pathways in such tumors.

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.