M Contini

Ameloblastic fibro-odontoma. Case report and review of the literature *

Ameloblastic fibro-odontoma (AFO) is defined by the World Health Organization (WHO) as a neoplasm composed of proliferating odontogenic epithelium. It is a benign, slow-growing, expansive tumour that clinically appears as a well-encapsulated, benign lesion. Histologically, AFO has been classified as an ameloblastic fibroma or odontoma. Despite numerous efforts, however, there is still considerable confusion concerning the nature, the histology and the therapy of these lesions. This paper reports an additional case of a large AFO and reviews the relevant literature regarding the clinical and pathologic features of this lesion.

Tyrosine kinase receptor status in endometrial stromal sarcoma: an immunohistochemical and genetic-molecular analysis.

Endometrial stromal sarcomas (ESS) are rare uterine malignant mesenchymal neoplasms, which are currently treated by surgery, as effective adjuvant therapies have not yet been established. Tyrosine kinase inhibitors have rarely been applied in ESS therapy, with few reports describing imatinib responsivity. The aim of this study was to analyze the status of different tyrosine kinase receptors in an ESS series, in order to evaluate their potential role as molecular targets. Immunohistochemistry was performed for EGFR, c-KIT, PDGFR-&agr;, PDGFR-&bgr;, and ABL on 28 ESS. EGFR, PDGFR-&agr;, and PDGFR-&bgr; gene expression was investigated by real-time polymerase chain reaction (qRT-PCR) on selected cases. “Hot-spot” mutations were screened for on EGFR, c-KIT, PDGFR-&agr;, and PDGFR-&bgr; genes, by sequencing. All analysis was executed from formalin-fixed, paraffin-embedded specimens. Immunohistochemical overexpression of 2 or more tyrosine kinase receptors was observed in 18 of 28 tumors (64%), whereas only 5 tumors were consistently negative. Gene expression profiles were concordant with immunohistochemical overexpression in only 1 tumor, which displayed both high mRNA levels and specific immunoreactivity for PDGFR-&agr;, and PDGFR-&bgr;. No activating mutations were found on the tumors included in the study. This study confirms that TKRs expression is frequently observed in ESS. Considering that the responsiveness to tyrosine kinase inhibitors is known to be related to the presence of specific activating mutations or gene over-expression, which are not detectable in ESS, TKRs immunohistochemical over-expression alone should not be considered as a reliable marker for targeted therapies in ESS. Specific post-translational abnormalities, responsible for activation of TKRs, should be further investigated.

S-100A1 Is a Reliable Marker in Distinguishing Nephrogenic Adenoma From Prostatic Adenocarcinoma

Nephrogenic adenoma is a benign lesion that may occur at any site of the genitourinary tract, usually in association with previous urothelial injuries. Although its pathogenesis is still debated, recent studies seem to confirm its derivation from renal tubular epithelium, rather than from a metaplastic process of urothelium. In addition to its uncertain origin, there can be diagnostic difficulty in distinguishing nephrogenic adenoma from prostatic adenocarcinoma, particularly with lesions arising in the prostatic urethra. So far, immunohistochemical stains are often needed to make such a distinction, and several markers have been proposed, often with controversial results. S100A1 is a calcium binding protein that has been recently reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms. Alpha-methylacyl-CoA racemase (AMACR), a recently identified prostate cancer marker, has also been found to be expressed in renal tubules and in some renal epithelial neoplasms. In this study, we investigated the expression of S100A1 and AMACR in 18 nephrogenic adenomas and in 100 prostatic adenocarcinomas. A strong and distinct cytoplasmic or nucleocytoplasmic staining of S100A1 was found in 17 out of 18 cases of nephrogenic adenoma (94%), but never in prostatic adenocarcinoma. In contrast, AMACR expression was detected in 14 of 18 nephrogenic adenomas (78%) and in 96 of 100 prostatic adenocarcinomas (96%). We conclude that (1) S100A1 is a specific and sensitive immunohistochemical marker to differentiate nephrogenic adenoma from prostatic adenocarcinoma; (2) AMACR immunostaining does not seem to be a useful marker in distinguishing between these 2 lesions; (3) given that both S100A1 and AMACR have been reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms, our findings confirm the histogenetic relationship between nephrogenic adenoma and renal tubular epithelium.

High sensitivity of reverse-hybridization methodology in the detection of KRAS mutations from formalin-fixed paraffin-embedded colorectal cancer samples.

Colorectal cancer is ranked the third most common cancer worldwide in terms of incidence and the second in terms of mortality. Recent advances in therapeutic approaches to colorectal cancer have identified a potential role of anti-epidermal growth factor receptor (EGFR) targeted therapies as adjuvant treatment in advanced disease. New evidences showed that patients harboring KRAS mutations on codons 12 and 13 are not responsive to anti-EGFR monoclonal antibodies. Therefore, new mutational screening tools have been proposed to select patients who will benefit from anti-EGFR targeted therapy, reducing inappropriate, expensive treatments and unwarranted side effects. We evaluated the performance of a reverse-hybridization-based assay in the identification of the most frequent KRAS mutations on a series of 50 formalin-fixed, paraffin-embedded, advanced colorectal cancer specimens, in comparison with the direct gene sequencing technique. Thirty-two of the 50 cases (64%) showed KRAS single point mutations by reverse-hybridization technique. In particular, 93.8% of the mutations were reported on codon 12, whereas 6.2% of the mutations were reported on codon 13. Direct gene sequencing showed KRAS mutations on 28 of the 50 cases (56%) with 96.4% of the mutations on codon 12 and 3.6% on codon 13. Concordance between the assays was observed in 92% of the cases. Both reverse hybridization and gene sequencing methods have been shown to be suitable tests in detecting KRAS mutations from formalin-fixed, paraffin-embedded tumor specimens. In our experience, reverse-hybridization technique has been shown to be an effective and more sensitive assay for the identification of the most common KRAS mutations.