S-100A1 is a reliable marker in distinguishing nephrogenic adenoma from prostatic adenocarcinoma.
ABSTRACT 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.
- SourceAvailable from: Pablo Moscato[Show abstract] [Hide abstract]
ABSTRACT: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.PLoS ONE 08/2010; 5(8):e12262. DOI:10.1371/journal.pone.0012262 · 3.53 Impact Factor
Chapter: Prostate Gland[Show abstract] [Hide abstract]
ABSTRACT: This chapter provides a practical overview of frequently used markers in the diagnosis and differential diagnosis of both common and rare neoplasms of prostate gland with a specific focus on adenocarcinoma and its mimickers. The chapter contains 41 questions; each question is addressed with a table, concise note, and representative pictures if applicable. In addition to the literature review, the authors have included their own experience and tested numerous antibodies reported in the literature. The most effective diagnostic panels of antibodies have been recommended for many entities, such as CK7, PAX2, and MUC6 being suggested as the best diagnostic panel for distinguishing seminal vesicles from prostatic ductal adenocarcinoma and high-grade prostatic intraepithelial neoplasia. Furthermore, immunophenotypes of normal prostate and seminal vesicles have been described, which tend to be neglected in the literature. KeywordsProstatic adenocarcinoma-P504S (AMACR)-PSA-PAX2-PIN4 (triple stain)Handbook of Practical Immunohistochemistry, 06/2011: pages 299-319;
- [Show abstract] [Hide abstract]
ABSTRACT: Nephrogenic adenoma (NA) is an uncommon and intriguing lesion in the urinary tract. The pathogenesis of NA is not entirely clear. NA was considered to be a metaplastic process of the urothelium in response to chronic irritation of the urinary tract. However, recent evidence has shown that NA is not a metaplastic lesion but rather a proliferation of exfoliated and implanted renal epithelial cells in the urinary tract. Histologically, NAs exhibit, singly or in combination, tubules, small papillae, and microcystic structures lined by cells with little cytological atypia and focal hobnail changes. Solid formations and compressed spindled cells within a fibromyxoid background are rarely observed. Differential diagnosis includes, but is not limited to, malignant neoplasms occurring at the same sites, in particular urothelial carcinoma with deceptively bland morphology (with small tubules, microcystic and nested variants), prostatic adenocarcinoma, and clear cell adenocarcinoma. Immunohistochemical studies with antibodies targeting members of the paired box gene family (PAX2 and/or PAX8) in NAs may be helpful in the differential diagnosis of urothelial lesions and prostatic adenocarcinoma. NAs are most likely to be confused with clear cell adenocarcinoma, especially in small biopsy specimens. This is confounded by both lesions being frequently positive for PAX2, PAX8, and CK7 and not infrequently positive for p504S (α-methylacyl-CoA-racemase, AMACR) by immunohistochemistry. Recognition of its characteristic morphological patterns and awareness of its unusual architectural and cytological features are important in making the diagnosis of NA and distinguishing this lesion from its mimickers.International Journal of Surgical Pathology 03/2012; 20(2):123-31. DOI:10.1177/1066896912439095 · 0.96 Impact Factor