Imaging in situ breast carcinoma (with or without an invasive component) with technetium-99m pentavalent dimercaptosuccinic acid and technetium-99m 2-methoxy isobutyl isonitrile scintimammography

INTRODUCTION: The aim of the study was to retrospectively define specific features of the technetium-99m pentavalent dimercaptosuccinic acid ((99m)Tc-(V)DMSA) and technetium-99m 2-methoxy isobutyl isonitrile ((99m)Tc-Sestamibi [(99m)Tc-MIBI]) distribution in ductal breast carcinoma in situ and lobular breast carcinoma in situ (DCIS/LCIS), in relation to mammographic, histological and immunohistochemical parameters. MATERIALS AND METHODS: One hundred and two patients with suspicious palpation or mammographic findings were submitted preoperatively to scintimammography (a total of 72 patients with (99m)Tc-(V)DMSA and a total of 75 patients with (99m)Tc-Sestamibi, 45 patients receiving both radiotracers). Images were acquired at 10 min and 60 min, and were evaluated for a pattern of diffuse radiotracer accumulation. The tumor-to-background ratios were correlated (T-pair test) with mammographic, histological and immunohistochemical characteristics. RESULTS: Histology confirmed malignancy in 46/102 patients: 20/46 patients had DCIS/LCIS, with or without coexistent invasive lesions, and 26/46 patients had isolated invasive carcinomas. Diffuse (99m)Tc-(V)DMSA accumulation was noticed in 18/19 cases and (99m)Tc-Sestamibi in 6/13 DCIS/LCIS cases. Epithelial hyperplasia demonstrated a similar accumulation pattern. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value for each tracer were calculated. Solely for (99m)Tc-(V)DMSA, the tumor-to-background ratio was significantly higher at 60 min than at 10 min and the diffuse uptake was significantly associated with suspicious microcalcifications, with the cell proliferation index ≥ 40% and with c-erbB-2 ≥ 10%. CONCLUSION: (99m)Tc-(V)DMSA showed high sensitivity and (99m)Tc-Sestamibi showed high specificity in detecting in situ breast carcinoma ((99m)Tc-(V)DMSA especially in cases with increased cell proliferation), and these radiotracers could provide clinicians with preoperative information not always obtainable by mammography

C-erb-B-2 oncoprotein and epidermal growth factor receptor in human hepatocellular carcinoma: An immunohistochemical study

The aim of this study was to evaluate the irnmunohistochemical expression of epidermal growth factor (EGFR) and c-erb-B-2 oncoprotein in a series of 71 hepatocellular carcinomas as well as in the adjacent hepatic tissue and to assess any correlation with HBsAg expression. The total of the 71 hepatocellular carcinomas (HCCs) was classified into 17 low grade and 54 high grade cases with adjacent non-neoplastic liver parenchyma, observed in 14 and 28 cases respectively. Coexisting cirrhosis or fibrosis was noticed in the adjacent non-neoplastic parenchyma in 12 cases of low grade and 22 cases of high grade HCC. The immunohistochemical avidin-biotin-peroxidase complex (ABC) method was performed on formalin-fixed paraffin sections for the detection of EGFR, c-erb-B-2 oncoprotein and HBsAg using monoclonal antibodies. The expression of c-erb-B-2 was observed in 29.5% (21171) of the HCCs showing no statistically significant correlation with histological grade. The c-erb-B-2 was also detected in the adjacent non-neoplastic parenchyma in 7/14 low grade HCCs, and in 9/28 high grade HCCs. No statistically significant differences in c-erb-B-2 oncoprotein expression were observed between the HCCs and the adjacent non-neoplastic parenchyma. In addition, HBsAg was detected in 10142 examined cases of HCC with adjacent non-neoplastic parenchyma, while only 4 cases of HCCs were simultaneously positive for c-erb-B-2 and HBsAg. EGFR was detected in only 3171 cases of HCC, while the antigen was not detected at al1 in the adjacent non neoplastic parenchyma. HBsAg expression was not observed in any of the EGFR-positive HCCs. Our results suggest that both c-erb-B-2-oncoprotein and EGFR do not seem to be predorninantly involved in the transformation of hepatocytes to the malignant phenotype

Statins and prostate cancer: Molecular and clinical aspects

The field of the potential applications of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) beyond their unambiguous cardiovascular beneficial effects is steadily increasing. In this regard, statins have also been shown to possess anti-inflammatory, immunomodulatory, antioxidant and growth inhibitory properties. Regarding their role in carcinogenesis, both preclinical and clinical studies report conflicting results. Intriguingly, accumulating evidence suggests that statins may relate to decreased prostate cancer incidence and recurrence risk. However, data from clinical studies seem to be still weak and are confounded by several factors. Nonetheless, preclinical data suggest that statins might exert a chemopreventive role against prostate cancer by inhibiting the proliferation and inducing apoptosis of prostate cancer cells and also inhibiting angiogenesis, inflammation and metastasis. Cholesterol lowering as well as statin pleiotropy through inhibition of the synthesis of isoprenoids have both been implicated in their anticancer properties. In this review, we discuss the preclinical and clinical evidence supporting the preventive or potentially harmful effects of statins on prostate tumourigenesis and conclude that statins should not be recommended for the prevention of prostate cancer development or progression based on the current data. (C) 2011 Elsevier Ltd. All rights reserved

Expression of HBsAg and HBsAg in liver tissue, correlation with disease activity

The pattems of Hepatitis B surface antigen (HBsAg) and Hepatitis B core antigen (HBcAg) expression were studied in liver biopsies taken from 41 patients with chronic HBV disease. Immunohistochemical methods were used on deparaffinized sections for the identification of HBsAg and HBcAg in liver tissue. lkenty-one of the 41 cases (5 1.2%) were classified as inactive liver disease and 20 (48.8%) as active liver disease. In liver biopsies with inactive disease, HBsAg demonstrated varying types of cytoplasmic expression in a rather high number of hepatocytes distributed mainly in clusters, while HBcAg was rarely expressed in liver nuclei. On the other hand, in liver biopsies with active disease HBsAg was characterized by a diffuse cytoplasmic expression in a few discrete hepatocytes, while HBcAg was expressed in the nuclei of the hepatocytes in 70% of the cases and in half of the positive cases it was also detected in the cytoplasm. In conclusion, HBsAg expression in a few scattered hepatocytes correlates with active liver disease and positive HBcAg, while varying HBsAg cytoplasmic expression in a rather high number of clustered hepatocytes is related to chronic inactive liver disease and negative expression of HBcAg

PAPOLA contributes to cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cell proliferation

Poly(A) polymerases add the poly(A) tail at the 3 ` end of nearly all eukaryotic mRNA, and are associated with proliferation and cancer. To elucidate the role of the most-studied mammalian poly(A) polymerase, poly(A) polymerase alpha (PAPOLA), in cancer, we assessed its expression in 221 breast cancer samples and found it to correlate strongly with the aggressive triple-negative subtype. Silencing PAPOLA in MCF-7 and MDA-MB-231 breast cancer cells reduced proliferation and anchorage-independent growth by decreasing steady-state cyclin D1 (CCND1) mRNA and protein levels. Whereas the length of the CCND1 mRNA poly(A) tail was not affected, its 3 ` untranslated region (3 ` UTR) lengthened. Overexpressing PAPOLA caused CCND1 mRNA 3 ` UTR shortening with a concomitant increase in the amount of corresponding transcript and protein, resulting in growth arrest in MCF-7 cells and DNA damage in HEK-293 cells. Such overexpression of PAPOLA promoted proliferation in the p53 mutant MDA-MB-231 cells. Our data suggest that PAPOLA is a possible candidate target for the control of tumor growth that is mostly relevant to triple-negative tumors, a group characterized by PAPOLA overexpression and lack of alternative targeted therapies

Lymphatic and blood vessel morphometry in invasive breast carcinomas: Relation with proliferation and VEGF-C and -D proteins expression

Introduction: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. Methods: Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. Results: Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008 respectively), while LV major axis, minor axis and the perimeter inversely correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively) and topoisomerase IIa (p=0.015, p=0.024 and p=0.045 respectively). The same LV parameters were found to positively correlate with cancerous VEGF-C (p<0.0001, p=0.092 and p=0.012 respectively) and VEGF-D in the stromal fibroblasts surrounding neoplastic cells (p=0.011, p=0.041 and p=0.026 respectively). High BVD exerted an unfavorable impact on both disease-free (p=0.021) and overall survival (p=0.031) of the patients. High LVD correlated with poor disease-free and overall survival only in the subgroup of patients with ER-negative tumors (p=0.056 and p=0.0312 respectively). Conclusion: These findings, for the first time, correlate lymphatic size with tumors of limited proliferative potential and higher nuclear differentiation. Moreover, they suggest that VEGF-C and -D expression influence lymphatic size rather than being involved in the increase of lymphatic vessel number

Cyclin D1 in invasive breast carcinoma: favourable prognostic significance in unselected patients and within subgroups with an aggressive phenotype

Aims: To study the clinicopathological and prognostic value of cyclin D1 overexpression in patients with breast carcinoma. Methods and results: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 290 invasive breast carcinomas to detect the proteins cyclin D1, oestrogen receptor (ER), progesterone receptor (PR), p53, c-erbB2, and topoisomerase IIa (topoIIa). Cyclin D1 staining was quantified using a computerized image analysis method. Cyclin D1 overexpression characterized smaller, ER-positive and PR-positive tumours (P = 0.017, P &lt; 0.0001, and P &lt; 0.0001, respectively), of a lower histological and nuclear grade (P = 0.011 and P &lt; 0.0001, respectively), and with reduced expression of topoIIa (P = 0.001) and p53 (P &lt; 0.001). Cyclin D1 was found to have an independent favourable impact on the overall survival of both the unselected cohort of patients (P = 0.011) and of patients with ER-negative and lymph node-positive tumours (P = 0.034 and P = 0.015, respectively). In triple-negative tumours, cyclin D1 overexpression was found to have independent favourable impacts on both overall and relapse-free survival (P = 0.002 for both). Conclusions: This is the first immunohistochemical study to dissociate the advantageous prognostic effect of cyclin D1 overexpression from its association with ER expression, and to provide evidence that cyclin D1 overexpression may be a marker of prolonged survival in patient subgroups with aggressive phenotypes