Vincenzo Nardini

FHIT and p53 gene abnormalities in bronchioloalveolar carcinomas. Correlations with clinicopathological data and K-ras mutations

Bronchioloalveolar carcinoma (BAC) is a particular type of adenocarcinoma of the lung which accounts for up to 9 per cent of pulmonary malignancies. The aetiology and pathogenesis of this unique neoplastic disease are still unclear. Three histological subtypes of BAC have been recognized: mucinous, non‐mucinous, and sclerosing. Of these, mucinous and sclerosing BAC have a worse prognosis than non‐mucinous tumours. The different morphological patterns and clinical outcomes of the subtypes of BAC suggest differences in their biological behaviour. Previous reports have shown that the mucinous form of BAC is characterized by constant mutations at codon 12 of the K‐ras gene, whereas the other two histotypes show a frequency of K‐ras mutations which is not different from that observed in conventional lung adenocarcinomas. The present study of a series of 51 BACs, previously investigated for K‐ras gene mutations, has evaluated the status of two other genes, p53 and FHIT, known to be frequently altered in non‐small cell lung cancer. Loss of heterozygosity at microsatellite‐containing loci located within the FHIT gene was observed in 22 (43 per cent) BACs. The distribution of FHIT gene abnormalities was not statistically different in the three histological subtypes. p53 mutations were present in 13 (32 per cent) non‐mucinous/sclerosing BACs, while no mutations were seen in mucinous tumours (P‐0·039). Correlations with clinicopathological parameters showed that p53 mutations in BACs are associated with more aggressive tumours. No correlations were observed between FHIT or K‐ras gene abnormalities and clinicopathological data. In conclusion, these results indicate that FHIT alterations are frequently involved in BAC tumourigenesis and that genetic changes in the p53 and K‐ras genes can distinguish between different histotypes of BAC.

Constitutive expression of cyclooxygenase-2 in the neuromuscular compartment of normal human colon

Abstract  Prostaglandins regulate various functions throughout the gastrointestinal system. Their biosynthesis depends on cyclooxygenase isoforms, named COX‐1 and COX‐2. The initial hypothesis that COX‐2 is an inducible enzyme has been challenged and its constitutive expression in the stomach has been established. In this study, an immunohistochemical analysis was performed to evaluate the distribution and cellular localization of COX‐2 in normal human colon. Colonic surgical specimens were processed for COX‐2, protein HuC/HuD, neurofilament, S‐100 protein and CD117/c‐kit immunodetection. COX‐2 protein was found to be constitutively expressed in the colonic wall: detectable amounts were localized in mucosal, submucosal and muscular layers, mainly in the neuromuscular compartment. In particular, COX‐2 was expressed in muscularis mucosae, submucosal ganglia, longitudinal muscle layer and myenteric ganglia, the neurons of which displayed different degrees of immunostaining. Intramuscular interstitial cells of Cajal, regarded as important sites for the regulation of enteric neuromuscular activity, were also partly COX‐2 immunoreactive. This study provides a detailed mapping of COX‐2 expression in human colon, and allows better understanding of the roles played by this isoenzyme in gut physiology.

Spermatogenesis in azoospermic, formerly cryptorchid men. Use of needle aspiration techniques.

OBJECTIVE To assess the use of testicular needle aspiration techniques to evaluate fertility potential in azoospermic, formerly cryptorchid men. STUDY DESIGN Fifteen consecutive adult azoospermic, formerly cryptorchid patients (eight unilateral and seven bilateral) were examined by needle aspiration techniques, fine (FNA) and large needle (LNAB) testicular aspiration biopsy, for cytologic and histologic analysis. Five of the 15 subsequently underwent surgical biopsy for attempted assisted fertilization. RESULTS Spermatozoa or spermatids were detected by FNA cytology or LNAB histology in one or both testicles in 87.5% of the unilateral and 28.6% of the bilaterally affected, formerly cryptorchid patients (P = .041, Fishers exact test). The addition of LNAB to FNA identified spermatids in one patient with unilateral cryptorchidism and only Sertoli cells on FNA cytology. Furthermore, LNAB differentiated testicles with the cytologic finding of only Sertoli cells into those with or without diffuse fibrosis. In the five patients in whom assisted fertilization was attempted, the needle aspiration techniques predicted the presence or absence of spermatozoa in the subsequent surgical biopsy. CONCLUSION The two needle aspiration techniques can be used to assess the fertility potential of azoospermic, formerly cryptorchid men and to select patients for assisted fertilization.

Presence of endothelin-1 in the normal and pathological human thyroid

An immunohistochemical study with two rabbit polyclonal antibodies I-AR76 and CA-08-351 against Endothelin-1 (ET-1) was performed in 133 human thyroid specimens: 5 normal thyroids, 30 multinodular goiters (15 toxic and 15 nontoxic), 20 Graves’ diseases, 5 Hashimoto’s thyroiditis, 26 adenomas (6 Hürthle cell, 16 toxic and 4 nontoxic), 30 classic papillary carcinomas, 3 minimally invasive follicular carcinomas, 1 widely invasive follicular carcinoma, 3 undifferentiated carcinomas and 10 medullary carcinoma. All normal thyroids, non toxic multinodular goiters and non toxic adenomas, 4 (66%) Hürthle cell adenomas, 3 (15%) Graves’ diseases, 1 (33%) case of minimally invasive follicular carcinoma showed rare follicular cells with weak cytoplasmic immunoreactivity. Many immunoreactive follicular cells, with or without oxyphilic changes, were observed in all specimens of Hashimoto’s disease, while the lymphocytic infiltrate was always negative. Twenty-seven (90%) classic papillary carcinomas were positive. Immunoreactivity was intra-cytoplasmic, weak in 14 cases and intense in 13. The cells of toxic adenoma and toxic multinodular goiter were negative, whereas the acellular stroma was intensely positive in both cases. Medullary and undifferentiated carcinomas were negative. These results show ET-1 immunoreactivity in normal and pathological human thyroids. In particular, the high content of this peptide in the thyroid papillary carcinoma suggests that ET-1, whose mitogenic role has recently been emphasized, could be involved in the growth of this tumor.

Drug addiction during pregnancy: Correlations between the placental health and the newborn's outcome – Elaboration of a predictive score

During pregnancy, drug addiction represents one of the most dangerous situations. Each drug can badly affect the fetal development and, when the pregnancy is over, the negative influence continues in the newborn which is exposed to many risks, in particular the withdrawal syndrome. Since it is difficult to predict the newborns outcome only on the basis of the kind of drug assumed by the mother during pregnancy, we propose the idea of a score based on the placentas state of health. The aim of the study is to correlate the placental score to the withdrawal symptoms graveness. Our retrospective study includes 35 newborns exposed in uterus to illegal and legal drugs. We used the Finnegans scoring system to quantify withdrawal symptoms and the placental score, based on the anatomopathological analysis, to assess the placentas health. The newborns included in our study have been divided into two groups depending on the result of the placental score (≤2 or ≥3). We found a significant statistical difference between the newborns whose placental score was low (≤2) and those whose score was high (≥3): the second group showed severe withdrawal symptoms for a longer time during the hospital stay (p = 0.014).

Sudden unexpected perinatal collapse and sudden unexpected early neonatal death

Acute neonatal events, ranging from mild episodes (characterised by collapse) to deadly episodes, are reported in literature more and more frequently. These events, which are defined as sudden unexpected perinatal collapse (SUPC) and sudden unexpected early neonatal death (SUEND) respectively, mainly occur in the first hours of life and usually affect infants from a first pregnancy who in most cases share the bed with their mothers. Due to the risks of severe neurological consequences or even death of the infant, it is essential for birth-centre staff to be adequately trained to ensure safe rooming-in.

P38.04: Indirect sonopraphic signs of fetal intracranial arteriovenous malformation

Objectives: The term macrocephaly signifies a head circumference (HC) that is more than 2 standard deviations above the mean or exceeds the 97th percentile. Benign familial macrocephaly is a dominantly or recessively inherited disorder in which the head size of otherwise normal newborn. In this study we report prenatal diagnosis of a benign familial macrocephaly case. Methods: The patient was a 20-year-old woman, gravida 1. She had an ultrasound examination at 11 weeks’ gestation. Ultrasound scanning at 18 weeks’ gestation showed a HC measurement above 97th percentile. Femoral length and abdomen circumference measurement were above 50th percentiles. Results: The serial scans demonstrated that HC had continued to growth above 97th percentile. Paternal HC was 62 cm (above 97th percentile) and family pedigree showed more than 14 other affected members with this disorder. At gestational age of 37+5 weeks, because of the large head size and premature rupture of membranes Cesarean section was performed and evaluation of the male infant at birth showed a HC 39 cm (above 98th percentile). No other physical abnormalities were detected. Follow-up evaluation by MRI and physical examination at 6 months of age showed a normal neurologic evaluation but persistent macrocephaly. Conclusion: In this disorder, serial measurement of HC demonstrates a proportional rather than an excessive rate of growth. In this condition, measurements of parental head size often reveal macrocephaly in one parent. This case report highlights the necessity of combining appropriate family history and serial measurement of HC for diagnosis of benign familial macrocephaly.