Clinical significance of PTEN and p-Akt co-expression in HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies

Objective: The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3'-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies. Methods: Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry. Results: PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05). Conclusion: In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies

A divergent role for estrogen receptor-beta in node-positive and node-negative breast cancer classified according to molecular subtypes: an observational prospective study

Introduction: Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PgR) are consolidated predictors of response to hormonal therapy (HT). In contrast, little information regarding the role of estrogen receptor-beta (ER-beta) in various breast cancer risk groups treated with different therapeutic regimens is available. In particular, there are no data concerning ER-beta distribution within the novel molecular breast cancer subtypes luminal A (LA) and luminal B (LB), HER2 (HS), and triple-negative (TN). Methods: We conducted an observational prospective study using immunohistochemistry to evaluate ER-beta expression in 936 breast carcinomas. Associations with conventional biopathological factors and with molecular subtypes were analyzed by multiple correspondence analysis (MCA), while univariate and multivariate Cox regression analysis and classification and regression tree analysis were applied to determine the impact of ER-beta on disease-free survival in the 728 patients with complete follow-up data. Results: ER-beta evenly distributes (55.5%) across the four molecular breast cancer subtypes, confirming the lack of correlation between ER-beta and classical prognosticators. However, the relationships among the biopathological factors, analyzed by MCA, showed that ER-beta positivity is located in the quadrant containing more aggressive phenotypes such as HER2 and TN or ER-alpha/PgR/Bcl2- tumors. Kaplan-Meier curves and Cox regression analysis identified ER-beta as a significant discriminating factor for disease-free survival both in the node-negative LA (P = 0.02) subgroup, where it is predictive of response to HT, and in the node-positive LB (P = 0.04) group, where, in association with PgR negativity, it conveys a higher risk of relapse. Conclusion: Our data indicated that, in contrast to node-negative patients, in node-positive breast cancer patients, ER-beta positivity appears to be a biomarker related to a more aggressive clinical course. In this context, further investigations are necessary to better assess the role of the different ER-beta isoforms

Vulvar "proximal-type" epithelioid sarcoma: report of a case and review of the literature

The "proximal-type" epithelioid sarcoma is a very rare kind of mesenchimal tumor characterized by the difficulty in histological diagnosis and the very aggressive biological behavior

Transforming growth factor-beta expression in prostatic noplasia

OBJECTIVE: To understand the role of transforming growth factor (TGF) -beta 1, -beta 2 and -beta 3 proteins and TGF-beta type I and II receptors in prostate neoplasia; to determine the correlation between expression of TGF-beta s and their relative receptors in the epithelial and stromal compartments of benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostate carcinoma; and to determine whether TGF-beta and TGF-beta receptor expression is associated with the grade of tumor differentiation. STUDY DESIGN: Sixty prostate neoplasms were analyzed by immunohistochemistry using anti-TGF-beta 1, -beta 2, -beta 3, -beta RI and -beta RII antibodies. RESULTS: TGF-beta and TGF-beta receptor immunoreactivity was more strongly expressed in prostate carcinoma than in PIN and BPH, and TGF-beta type I and type II receptors were less strongly expressed than TGF-beta 1-3 proteins. The difference between epithelial and stromal compartments reached significance (P < .05) for all TGF-beta isoforms and related receptors only in BPH, whereas a significant difference was found for TGF-beta protein in all grades of PIN but not for prostate carcinoma tissue. Luminal epithelial cells of BPH and PIN coexpressed all three TGF-beta isoforms and preferentially TGF-beta RII. Conversely, basal epithelial cells stained strongly for TGF-beta 1, -beta 3 and -beta RI but not for TGF-beta 2 and more strongly for TGF-beta RI than -beta RII. Linear regression showed a positive correlation between TGF-beta 1 and -beta 2, between TGF-beta 2 and -beta 3 and between TGF-beta RI and -beta RII proteins in all areas. The epithelium of Gleason score 7 tumors contained significantly higher TGF-beta 2 protein levels than Gleason score 3 and 4, and 5 and 6 tumors (P < .05). CONCLUSION: Stromal and epithelial cells of malignant and nonmalignant prostatic tumors express all three TGF-beta isoforms and their related receptors. These may act as both paracrine and autocrine factors to influence prostate function and the stromal-epithelial cell interaction. TGF-beta and -beta R immunoreactivity noted in basal cells indicates that in BPH and PIN, TGF-beta Rs and signaling pathways remain intact. The overexpression of TGF-beta proteins and underexpression of TGF-beta receptors in prostate cancer could suggest a mechanism for prostate cancer cells to escape the growth inhibitory effect of TGF-beta, thus leading to a more malignant phenotype

Comparative analysis of a plastination specimen and clinical diagnostic images.

JISP vol 8(1) 1994 Comparative Analysis of a Plastination Specimen and Clinical Diagnostic Images Maurizio Ripani, Andrea Bassi, Letizia Perracchio, Maria Letizia Boccoa, Giampaolo Tomaselli, Laura Giacomelli, Silvio Messinet and Giulio Marinozzi Summary An invasive apocrine carcinoma of the perineal glands, involving the anal canal, vagina and vulva was surgically removed from a 62 year-old woman. The specimen was plastinated and macroscopically sectioned serially. The sections were photographed and compared to CT images made prior to surgery to verify and support the accuracy of the clinical diagnostic images

First-line liver resection and salvage liver transplantation are increasing therapeutic strategies for patients with hepatocellular carcinoma and child a cirrhosis.

The present study focused on nine patients with hepatocellular carcinoma (HCC) associated with Child A liver cirrhosis undergoing first-line liver resection and salvage liver transplantation (SLT) for liver tumor recurrence.Forty-six patients with HCC underwent liver transplantation (OLT); 37 (80.5\%) were primary liver transplantations (PLTs) and 9 (19.5\%) were SLTs. All patients who underwent SLT received minor transabdominal liver resections.The posttransplant 1-, 3-, and 5-year overall survival rates for SLT (88.9\%, 88.9\%, and 88.9\%) were similar to those for PLT (78\%, 62.7\%, and 62.7\%). Four (10.8\%) patients in the PLT group had HCC recurrence, while there was zero recurrence in the SLT group. The 1-, 3-, 5-year disease-free survival rates for PLT (89\%, 74\%, and 74\%) were similar to those for SLT (100\%, 100\%, and 100\%). The 1-, 3-, 5-year disease-free survival rates after PLT were 89\%, 74\%, and 74\%, and after SLT were 100\%, 100\%, and 100\%, respectively. The operative mortality, intraperioperative bleeding, operative time, intensive care unit stay, in-hospital stay, and overall incidence of postoperative complications were similar in the two groups.In our experience, SLT for HCC is a feasible procedure with similar results in terms of overall survival, disease-free survival, and postoperative complications to those reported for patients who underwent PLT at our institute. An important role exists for SLT as shown by the fact that such a strategy has been used in the 20\% of the patients undergoing OLT for HCC

Clinical significance of PTEN and p-Akt co-expression in HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies

Objective: The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3′-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies. Methods: Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry. Results: PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05). Conclusion: In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies