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Background. P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. Methods. By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). Results. In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. Conclusions. We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.

Objective. Upon binding with HGF, the thyrosine-kinase receptor c-met induces cell growth, scattering and morphogenic effects via the trasducers STAT3 and phosphorylated-STAT3, PI3K/Akt, Rho. HGF, c-met and STAT3 are expressed with very high frequency in papillary thyroid carcinomas (PTC), suggesting a role in PTC. Herein we first investigate the simultaneous expression of HGF, c-met, STAT3, phosphor-STAT3, PI3K, Akt and Rho in thyroid nodules. Design and methods. Using immunohistochemistry, we studied: 30 colloid nodules (CN), 18 hyperplastic nodules (HN), 20 follicular adenomas (FA), 15 oncocytic adenomas (OA), 20 PTC, 16 follicular carcinomas (FTC) and 6 anaplastic carcinomas (ATC). Results. All 7 proteins were expressed in 15% of FA (with HGF, PI3K and Rho stromal reactivity) and 25% of PTC, and the combination HGF/c-met/STAT3/ pSTAT3/PI3K was expressed by all PTC, each protein being expressed by tumor cells. In contrast, 13/16 FTC (81%) exhibited immunoreactivity for PI3K (both epithelial and stromal), and 100% of ATC was PI3K+ (both epithelial and stromal) and Rho+ (epithelial). Epithelial expression of PI3K correlated with the clinical behavior of histotypes and, within FTC, the proportion of PI3K+ cells correlated with both the clinical and pathological stage (r=0.95; p

TNM post-surgical staging is considered to be one of the most powerful prognosticators for colorectal carcinoma. Although patient survival mostly decreases concomitantly to stage increase, in a percentage of cases TNM stage appears only to express the anatomic extent of the neoplasia with no correlation with clinical outcome. Thus, the identification of additional prognostic markers for colorectal cancer is required. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that appears to play an important role in colorectal cancer progression. In order to evaluate whether NGAL expression may be considered as a predictor of colorectal cancer progression, we analyzed its correlation with clinicopathological characteristics, as well as with patient progression-free survival in a series of surgically resected colorectal carcinomas. A variable NGAL immunoexpression was found in 24 out of the 64 analyzed cases. When only the positive cases were considered, a significant association was found between a high NGAL expression and the presence of distant metastases or high tumor stage. In addition, the presence of NGAL was a significant negative prognostic marker correlated with a shorter progression-free survival in stage I colorectal carcinoma, but not in the remaining TNM stages. If our findings are confirmed in more extensive analyses on stage I colorectal carcinoma, NGAL assessment may be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.

Caveolin-1 (cav-1) has been proposed as an immunohistochemical marker able to distinguish astroglial from oligodendroglial tumors. In addition, it has been suggested that the reduction of caveolin-1 expression in glioblastoma cells increases their proliferative and invasive potential. Accordingly, the present study investigates caveolin-1 immunoexpression and correlation with the 1p/19q status, histologic grade, proliferation index, epidermal growth factor receptor, and p53 expression in a series of 73 diffuse gliomas. A membranous and cytoplasmic immunolabeling for caveolin-1 was detected in neoplastic cells of 60% of cases. No significant differences in terms of caveolin-1 expression were observed between astrocytomas, oligodendrogliomas, and oligoastrocytomas. In addition, caveolin-1 expression was not correlated with 1p/19q status in oligodendrogliomas and mixed oligoastrocytomas. Caveolin-1 was expressed in most high-grade (World Health Organization III and IV) gliomas. Low caveolin-1 expression correlated with a higher Ki-67 labeling index and the absence of p53 overexpression in glioblastomas, and it was significantly associated with epidermal growth factor receptor overexpression in anaplastic astrocytomas. In conclusion, the present study indicates that caveolin-1 is not useful as diagnostic marker to differentiate grade II astrocytomas from oligodendrogliomas.

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 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, postmenopausal 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.

Müllerianosis is a term used to indicate lesions composed of an admixture of two or three types of müllerian-derivation glands in heterotopic sites. In this report we describe a case of spinal cord müllerianosis which occurred in a 42-year-old woman. The patient had suffered from catamenial lumbago and sciatica of three years duration before undergoing laminectomy of L2-L3 with excision of a polypoid mass that compressed nerve trunks. At histological examination, the lesion was composed of endocervical, endometrial and tubal glands within a smooth muscle nodule. These features were consistent with a diagnosis of müllerianosis. This is a very uncommon form of presentation of müllerianosis that must be correctly identified since patients can benefit from hormonal therapy.