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The classification of poorly differentiated carcinomas involving the renal medullary/sinus region might be challenging on conventional histomorphologic grounds alone. However, delineation of high-grade renal cell carcinomas such as collecting duct (Bellini) carcinoma from urothelial cell carcinoma of the renal pelvis is critical, as it conveys important therapeutic implications. We assessed the so far neglected differential diagnostic role of protein gene product 9.5, a neuropeptide involved in intracellular proteolysis, in terms of differentiating invasive urothelial cell carcinomas of the renal pelvis from high-grade renal cell carcinomas infiltrating the renal medullary/sinus region. To this aim, 21 invasive urothelial cell carcinomas of the renal pelvis and 27 high-grade renal cell carcinomas (8 renal cell carcinomas with sarcomatoid dedifferentiation and 5 type 1 and 7 type 2 papillary renal cell carcinomas as well as 7 collecting duct carcinomas) were stained with antibodies directed against protein gene product 9.5, CD10, vimentin, CEA, p63, CK5/6, CK7, CK20, PAX2, PAX8, CD117 (c-Kit), AE1/3, α-methyl CoA racemase, actin, and desmin. Briefly, strong protein gene product 9.5 expression was observed in 6 (86%) of 7 collecting duct carcinomas, 8 (67%) of 12 papillary renal cell carcinomas, and 2 (25%) of 8 renal cell carcinomas with sarcomatoid dedifferentiation. Conversely, none of the 21 urothelial cell carcinomas investigated showed protein gene product 9.5 expression. Our findings suggest that protein gene product 9.5, particularly if used in conjunction with p63 and CK5/6, might be helpful in differentiating high-grade renal cell carcinomas from urothelial cell carcinomas of the renal pelvis, whereas its specificity with respect to the histologic subtyping of renal cell carcinomas seems to be low. However, because of the limited number of study cases enrolled in our investigation, our findings need to be validated in the future., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The family of the poly(adenosine diphosphate-ribose) polymerase (PARP) proteins is directly involved in genomic stability, DNA repair, and apoptosis by DNA damage. In this study, we evaluated the role of PARP-1 in melanoma and its prognostic importance. We studied by immunohistochemistry and Western blot analysis PARP-1 expression in a selected series of 80 primary melanoma of the head and neck region. The results were correlated with tumor thickness and patient's outcome. A follow-up of at least 3 years was available. Fifteen cases of benign melanocytic nevi were used as controls. Normal melanocytes showed only scattered, focal nuclear positivity and were considered as negative for PARP-1 expression by immunohistochemistry (score, 0). Thirty cases of melanoma (37.5%) showed nuclear expression of PARP-1 in both radial and vertical growth phases. Western blot analysis showed the presence of a high signal for full-length PARP-1 only in the cases with high immunohistochemical (nuclear) expression of protein (score, ++/+++) in both radial and vertical growth phase. A significant correlation was present between PARP-1 expression in vertical growth phase and the thickness of tumor lesion (P = .014); all but one tumor measuring less than 0.75 mm showed no or low PARP-1 expression. No correlation was found between PARP-1 expression in radial growth phase and tumor thickness (P = .38, data not shown). These data suggest that PARP-1 overexpression is a potential novel molecular marker of aggressive cutaneous malignant melanoma and a direct correlation between PARP-1-mediated inhibition of the apoptosis and biologic behavior of cutaneous malignant melanoma.

The rare condition of women with erythrocytosis and a concurrent myomatous uterus has been classified as "myomatous erythrocytosis syndrome". Substantial myoma size has been noted as a common denominator in this condition in which recent evidence have confirmed erythropoietin (Epo) production by myoma tissues themselves. Apart from its primary endocrine role in controlling erythropoiesis, Epo has been demonstrated to mediate several cellular processes such as angiogenesis, mitogenesis, and inhibition of apoptosis by autocrine and paracrine mechanisms. Recently, Epo and its receptor (Epo-R) have been shown to be involved in the growth, viability, and angiogenesis of several malignant tumors including human female reproductive organ malignancies. In this paper, we researched on Epo and, as a first in the literature, Epo-R immunoexpression in a large uterine myoma of a term pregnant patient suffering from the myomatous erythrocytosis syndrome. Eight nongravidic leiomyomas and 8 gravidic leiomyomas were used as control group samples. Apart from confirming Epo production by myoma smooth muscle cells in the myomatous erythrocytosis syndrome, we reveal in this pathologic condition a characteristic strong Epo-R expression in myoma endothelial cells and a weak and sporadic Epo-R expression in myoma smooth muscle cells. The striking presence of Epo-R within myoma tissues in the case of the myomatous erythrocytosis syndrome allows us to speculate that myoma Epo production, besides determining erythrocytosis through systemic effects, may contribute, acting by autocrine and paracrine mechanisms, in determining the large myoma size almost always observed in this condition. Finally, we confirm a less but specific immunostaining for Epo in uterine myomas of patients without erythrocytosis and, as a first in the literature, we prove a weak and sporadic Epo-R expression in these lesions. These last results may contribute to knowledge of the yet unclear etiopathogenesis of the most common human gynecologic neoplasm.

The unopposed estrogen effect is the main cause of leiomyoma growth and is at the basis of the clinical use of gonadotropin-releasing hormone (GnRH) agonists. Platelet-derived growth factor (PDGF) has been indicated as the main growth factor involved, in vitro in the proliferation response of leiomyoma smooth muscle cells to estrogen stimulation. The aim of this article is to evaluate the mitogenic action of PDGF in vivo by studying the relationship between PDGF expression in leiomyomas and post-GnRH analogue treatment changes in uterine volume. Thirty-nine patients suffering from uterine leiomyomas were treated with leuprorelin acetate depot 3.75 mg for three cycles; 31 untreated patients were enrolled as control group. Uterine volume was determined twice by ultrasonography in each patient, the first time at admission and the second time after treatment in the study group and after 3 months in the control group. The change in the uterine volume was then evaluated. Patients underwent surgery, and PDGF immunohistochemical detection was performed on the obtained fibroid samples. Uterine volume decreased significantly after treatment, whereas just a poor modification was found in the controls. The decrease in the uterine volume was found to be statistically related to PDGF expression. Thus PDGF levels decreased in treated patients as compared with controls. The decreased PDGF production in leiomyomas after GnRH analogue treatment and the relationship between decreased PDGF expression and greater shrink age in uterine volume suggest that PDGF might have a mitogenic action on leiomyomas in vivo., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 25 oral squamous cell carcinoma (SCC) was investigated. The average age of the patients was 62.04 years (range, 27 to 81 years), with a sex ratio (M/F) of 23:2. The follow-up mean time was 2.24 years (range, 8 months to 8 years from surgery). Immunohistochemistry for PCNA, bcl-2, bcl-1, and bax proteins was carried out on 5-microm serial sections from formalin-fixed, paraffin-embedded tissue. The findings were compared with clinicopathologic data and with follow-up. The statistical evaluation of the results of the current study suggests that the low positivity for PCNA with a high positivity for bcl-2 protein are related to a better clinical behavior of the tumors. By converse, a high expression of PCNA, bax, and bcl-1 appears to correlate with a worse prognosis. All of our cases of SCC showed the presence of aneuploid populations, which was not correlated with the clinicopathologic parameters or with the overexpression of bcl-1, bcl-2, bax, and PCNA. Therefore, the aneuploidy per se did not predict the clinical evolution for the single cases of cancers. Nevertheless, once the parameters considered for the evaluation of DNA were examined in detail, it appeared that some of them, individually or combined with each other or with the expression of bcl-1, bcl-2, and bax, gained statistical significance in predicting the clinical evolution of SCC of our series. Particularly, high values of 2cDI and DNA-MG and the absence or reduction of the euploid population were associated with a short interval between surgery and recurrence or death, and this significance persisted when the simultaneous presence of overexpression of bcl-1 was considered.

Basal cell carcinoma (BCC) is currently the most common cutaneous cancer found in humans. Although it generally shows a relatively benign course (BCC1), some cases of BCCs show "aggressive" behavior, rapidly infiltrating deeper structures, or metastasizing (BCC2). Until now, the traditional histological diagnostic criteria have failed to discriminate unequivocally between BCC1 and BCC2. Therefore, there is still a need to find reliable prognostic indicators that correlate with outcome and may detect patients at high risk for BCC recurrence, or metastasis and death. Recent studies have suggested that there is a significant correlation between tumor angiogenesis, expressed as the microvessel density within and toward a tumor, tumor aggressiveness, and the overall survival of patients with solid tumors. In this study, the authors examined the angiogenic rate in human cutaneous BCCs, to establish if it correlates with their biological behavior. Vessels were highlighted by immunocytochemical staining for FVIII-related antigen in formalin-fixed, paraffin-embedded tissues. All BCC2 samples of this series showed a significantly higher microvessel count than did BCC1. The existence of a significant discrepancy between the neovascularization in BCC1 and BCC2 suggests that the angiogenetic process may be an important step in the acquisition of the aggressive (malignant) phenotype in human. BCCs. The findings of the present study seem to establish a correlation between tumor vascularization and clinicobiological parameters of aggressiveness in BCC. Considering the emerging studies on the possible clinical use of substances interfering with the angiogenetic process, it is possible that the local therapy for BCCs could become less destructive, with consequent improvement in the quality of life of these patients, apart from the prolongation of the overall survival. From this view-point, the assay of microvessel density might be helpful in selecting patients with cutaneous BCCs at high risk for recurrence or metastasis, who could benefit ab initio from additional therapies and closer follow-up.