Maddalena Grosso

PLEUROPULMONARY BLASTOMA: LONG-TERM SURVIVAL AND LITERATURE REVIEW

BACKGROUND AND PROCEDURE Pleuropulmonary blastoma (PPB) identifies different types of pulmonary tumors in the pediatric age. It is extremely uncommon and is known to have a very poor prognosis, with only few cases surviving after 10 years follow-up. Our experience with such a patient and long-term follow-up (12 years) is therefore of interest. She was a 2-year-old girl admitted with a history of respiratory distress and underwent a left thoracotomy. The tumor was removed and after 1 month a polychemotherapy course was started using dactinomycin and vincristine for 6 months. The patient remains disease-free 12 years after the operation. CONCLUSIONS The biologic behavior of the tumor is considered unpredictable, and for this reason much effort has been expended in trying to identify prognostic factors. The preoperative size of the mass (size <5 cm) in our patient, its complete excision, and the histologic aspects might be helpful in identifying favorable prognostic factors.

Hep Par 1 in gastric and bowel carcinomas: an immunohistochemical study

Aims: Hep Par 1 has been described as a specific marker of hepatocellular differentiation and its immunohistochemical use has been suggested as a helpful tool for hepatocellular carcinoma (HCC) diagnosis. Most metastatic liver tumours come from the gastrointestinal tract and usually can be distinguished from HCC only through histology. We evaluated by immunohistochemistry the specificity of Hep Par 1, studying the presence of the epitope that reacts with Hep Par 1 in primary gastric and colorectal cancers. Methods: A series of 39 cases of primary gastric and 18 cases of colorectal carcinoma were selected. Twenty‐six of the 39 gastric carcinomas were of the intestinal type, six of the diffuse type, three of the mixed type and five had hepatoid differentiation. Two of the 18 colorectal adenocarcinomas were well differentiated, 14 moderately differentiated, one poorly differentiated and one was of the mucinous type. Five‐ w m sections were stained by immunohistochemistry using Hep Par 1 as primary antibody. Results: Immunohistochemical staining was observed in 26 gastric carcinomas (69%) and nine large bowel carcinomas (50%). Fifteen of the 26 positive‐stained gastric cancers were of intestinal type, four of diffuse type and two of mixed type cases. All of the five hepatoid type cases stained positively. Two of the nine positively stained colorectal cancers were well differentiated, six were moderately differentiated and one was a mucinous type adenocarcinoma. The staining pattern was cytoplasmic and granular as described in benign and malignant hepatocytes. The percentage of immunostained cells was graded as follows: 0 (no staining); 1 (> 0‐5%); 2 (> 5‐50%); 3 (> 50%). Of the 26 positive gastric tumours, 13 showed a staining score of 1, eight scored 2, and five scored 3. Four of the nine positive intestinal carcinomas showed a staining score of 1, and five scored 2. Conclusions: Our results show that Hep Par 1 is a highly sensitive marker of hepatocellular differentiation as demonstrated by the expression in gastric tumours with hepatoid histotype. However, the frequent reaction with neoplastic cells of gastric and bowel carcinomas shows a low grade of specificity of this antibody.

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.

5-Lipoxygenase is Coexpressed with Cox-2 in Sporadic Colorectal Cancer: A Correlation with Advanced Stage

PurposeIt 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.MethodsExpression 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.Results5-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.ConclusionsOur 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.

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.

The immunoexpression of Tn, sialyl-Tn and T antigens in chronic active gastritis in relation to Helicobacter pylori infection

Summary The simple mucin‐type carbohydrate antigens Tn, sialyl‐Tn and T represent the mucin core oligosaccharide structures that are produced in the initial steps of mucin biosynthetic pathway. Utilising monoclonal antibodies anti‐Tn antigen, anti‐sialyl‐Tn antigen and anti‐T antigen, we have investigated the expression of the simple mucin‐type carbohydrate antigens in 47 biopsy specimens of antral mucosa with chronic active gastritis, 25 of which had Helicobacter pylori infection. The Tn immunoreactivity, localised at the supranuclear region of surface and glandular mucous cells, was observed in all samples, independently from H. pylori status. The sialyl‐Tn antigen, mainly localised in the cytoplasm of glandular mucous cells and in goblet cells vacuoles, was seen in 56% of the cases with H. pylori infection and in 41% of the cases in the H. pylori ‐negative group. In addition, the T antigen was found in the cytoplasm of surface and glandular mucous cells in 16% of the H. pylori ‐positive group, whereas the percentage of positive cases was reduced to 5% in H. pylori ‐negative patients, with an exclusive localisation in the cytoplasm of glandular mucous cells; after neuraminidase treatment, the percentage of T antigenpositive cases was increased to 28% in H. pylori ‐positive cases and to 27% in negative cases. No significant relationships between H. pylori infection and Tn, sialyl‐Tn or T antigen immunoexpression were encountered in our cases. Therefore, we maintain that the inflammatory infiltrate may itself play an important role in the expression of simple mucin‐type carbohydrate antigens in chronic active antral gastritis.

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

BackgroundCaveolin-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. DesignSamples 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. ResultsMyocardial 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. ConclusionsThis 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.

Chromophobe renal cell carcinoma in pregnancy: case report and review of the literature.

A 25-years old gravida 2, para 1001, came to our clinic in November 1998 at 10 weeks’ gestation because of a palpable mass in her left flank. Laboratory tests were normal and hematuria was not present. A sonogram, performed at admission, showed a 145¿137 mm complex mass under the spleen that prevented the study of the left kidney; annex and embryo (CRL 20 mm) were normal. Magnetic resonance imaging (T1-weighted with fat suppression) showed the presence of a 140¿180¿150 mm homogeneous mass, with clear outline, infiltrating the left kidney and displacing upward, without infiltration, the tail of pancreas (Fig. 1); no metastasis was demonstrated. The patient was transferred to the general surgical department and submitted to left radical nephrectomy with lymphadenectomy. At macroscopic examination (Fig. 2) the volume of left kidney appeared remarkably enlarged (180¿140 mm), with irregular surface, some hemorrhagic areas and solid consistency to the knife. The histological examination (Figs. 3, 4), performed on 5 micron sections included in paraffin and hematoxylin-eosin staining, demonstrated a compact architecture with poligonal cells of variable dimensions with evident cytoplasmatic mem-

Clear cell colorectal carcinoma: a case report with analysis of neo-angiogenesis

Dear Editor: Clear cell colorectal carcinoma is a rare oncological entity with only ten cases reported in the literature up to now. It generally affects elderly men and it is preferentially located in the left colon. In the present paper, we describe an additional case of this rare tumour. A 71-year-old womanwas admitted to our hospital because of tenesmus and lower abdominal pain. Her past clinical history included a surgical operation for meningioma, performed a year previously. Her family history was negative for both colorectal cancer and polyposis syndromes. Colonoscopy revealed the presence of a polypoid mass 3 cm in size located in the sigmoid colon. Abdominal ecography and computed tomographic scan found no abnormal findings in the liver, kidneys, genital tract, and ovaries. The patient underwent a low anterior resection and was discharged in good health. No recurrences developed during a 4-month follow-up. The gross examination of the surgical specimen disclosed a polypoid, ulcerated neoplasm. The sample was formalin fixed and paraffin embedded for the subsequent microscopic evaluation. The histological examination by haematoxylin and eosin staining revealed a tumour composed of cells with a clear cytoplasm, which were arranged in a tubuloglandular pattern and cribriform structures. The tumour involved the mucosa and infiltrated through the muscularis propria of the colonic wall. Numerous foci of necrosis were observed, whereas no peri-tumoural inflammatory infiltrate was evident. One of the 13 regional lymph nodes showed metastatic growth. The histological characteristics of the nodal metastasis were the same as those of the primary lesion. Periodic acid-Schiff, Alcian blue pH 2.5 and oil red O were not reactive. At the immunohistochemical assays, the neoplastic cells were positive for CDX2 (Dako Cytomation, Glostrup, Denmark), carcinoembryonic antigen (Dako Cytomation, Glostrup, Denmark) and cytokeratin 20 (Dako Cytomation, Glostrup, Denmark) and negative for cytokeratin 7 (Dako Cytomation, Glostrup, Denmark), vimentin (Dako Cytomation, Glostrup, Denmark) and CD10 (Dako Cytomation, Glostrup, Denmark), in line with their colonic derivation. A Ki-67 (Dako Cytomation, Glostrup, Denmark) staining was found in the nuclei of 30% of neoplastic cells. In an attempt to study the biological behaviour of this rare tumour, we also evaluated its microvessel density (MVD) through the immunohistochemical assessment of CD105 (Dako Cytomation, Glostrup, Denmark) and analysed the immunoexpression of the vascular endothelial growth factor (VEGF; Santa Cruz Biotechnology, Santa Cruz, CA, USA) and of the pro-angiogenic factor angiogenin I (Santa Cruz Biotechnology, Santa Cruz, CA, USA). A low MVD (ten microvessels per square millimetre) and a low VEGF (stained cells <20% of neoplastic cells) expression were found in this tumour. In addition, no staining for angiogenin I was evidenced in the neoplastic cells of this clear cell colorectal adenocarcinoma. Primary clear cell colorectal adenocarcinoma is a very rare entity, with only a few cases described so far. The adenoma–carcinoma sequence recognised for colorectal tumours seems also to be valid for colorectal clear cell Int J Colorectal Dis (2009) 24:1351–1352 DOI 10.1007/s00384-009-0716-0