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The prognostic relevance of estrogen (ER) and progesterone receptor (PR) expression in endometrioid endometrial cancer is still controversially discussed. The present study has focused on the evaluation of the prognostic value of ERα, ERβ1, ERβ2, and PR in this histotype. Specifically, we were interested in evaluating whether the relative level of ER subtype-specific expression (in terms of a ratio ERα/ERβ1 and ERα/ERβ2) would predict clinical outcome better than their absolute levels in patients with endometrioid endometrial cancer. To this end, protein content was assessed by immunohistochemistry in a group of 121 cases and staining was analyzed in relation to clinicopathologic variables, disease-free survival and overall survival. Results obtained have demonstrated that none of the biological markers analyzed possess an independent prognostic role with regard to disease-free survival. Multivariate analysis of overall survival has shown that ERα alone is not an independent prognostic indicator in patients with endometrioid endometrial cancer (hazard ratio [HR]; 0.5; 95% confidence interval [CI], 0.09-3.0; P = .5). On the other hand, an ERα/ERβ1 ratio of 1 or less or an ERα/ERβ2 ratio of 1 or less has proved to be independently associated with a higher risk of death (HR, 6.4 [95% CI, 1.0-40.6; P = .04] and 9.7 [95% CI, 1.1-85.3; P = .04], respectively) along with age, tumor stage, and Ki-67. In conclusion, we report here that the ERα/ERβ1 and ERα/ERβ2 expression ratios are independent prognostic markers of survival in endometrioid endometrial cancer; these findings suggest that phenotyping these interacting markers conjointly may better predict patient survival than each individual marker alone., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Activating mutations in the valine-to-glutamic acid substitution at position 600 of the v-raf murine sarcoma viral oncogene homolog B1 (BRAF-1) gene are detected frequently in patients with papillary thyroid carcinoma (PTC). These mutations have been identified in approximately 29% to 69% of PTCs and in >80% of PTCs of the tall cell variant, whereas they have not been detected in benign lesions or in the majority of those (80%) with the follicular variant of PTC. The objective of the current study was to evaluate the role of liquid-based cytology (LBC) for the detection of BRAF mutations in the outcome of patients who have thyroid PTC measuring ≤ 1 cm and, hence, in guiding their clinical and surgical management., Methods: From October 2010 through June 2011, 230 consecutive cases were diagnosed as positive for malignancy on fine-needle aspiration cytology processed by LBC. Of these, 73 PTCs ≤ 1 cm underwent BRAF mutational analysis. The aspirated material was processed using an LBC technique. After DNA extraction of the residual material, BRAF mutation analysis was performed using a direct sequencing method., Results: Fifty of 73 patients (68.5%) underwent surgery, and 34 of those patients (68%) had tumors that expressed a BRAF mutation (31 PTCs, including 11 tall cell variants and 3 follicular-variant PTCs). A significant association between BRAF mutation and bilaterality of cancer was observed (odds ratio, 0.077; P = .0007). BRAF mutation was associated significantly with lymph node involvement (odds ratio, 19; P = .0007) but not with extracapsular infiltration (odds ratio, 0.298; P = .179)., Conclusions: The current results indicated that BRAF gene mutations can be identified successfully on LBC material and using other cytologic methods with high reproducibility, feasibility, and informative results. The presence of a BRAF mutation may preoperatively predict the behavior of microscopic PTC, suggesting a more aggressive surgical approach., (Copyright © 2012 American Cancer Society.)

Some lines of evidence suggest that tumors, including ependymoma, might arise from a subpopulation of cells, termed cancer stem cells (CSCs), with self-renewal and tumor-initiation properties. Given the strict dependence of CSCs on epidermal growth factor (EGF) through EGF receptor (EGFR), we investigated the effects of EGFR inhibitors in ependymoma-stem cells (SCs) in vitro and in orthotopic mouse models. We established two ependymoma-SC lines from two recurrent pediatric ependymoma. Both lines expressed markers of radial glia--the candidate SCs of ependymoma--and showed renewal ability, multipotency, and tumorigenicity after orthotopic implantation, despite markedly different expression of CD133 (94 vs. 6%). High phosphorylated-EGFR/EGFR ratio was detected, which decreased after differentiation. EGFR inhibitors (gefitinib and AEE788) reduced clonogenicity, proliferation and survival of ependymoma-SC lines dose-dependently, and blocked EGF-induced activation of EGFR, Akt and extracellular signal-regulated kinase 1/2. Overall, AEE788 was more effective than gefitinib. EGFR blockade as well as differentiation strongly reduced CD133 expression. However, ex vivo treatment with AEE788 did not impair orthotopic tumor engraftment, whereas ex vivo differentiation did, suggesting that CD133 does not absolutely segregate for tumorigenicity in ependymoma-SCs. Orally administered AEE788 prolonged survival of mice bearing ependymoma-SC-driven orthotopic xenografts from 56 to 63 days, close to statistical significance (log-rank p=0.06). Our study describes for the first time EGFR signaling in ependymoma-SCs and the effects of EGFR blockade in complementary in vitro and in vivo systems. The experimental models we developed can be used to further investigate the activity of EGFR inhibitors or other antineoplastic agents in this tumor., (Copyright © 2011 UICC.)

The efficacy of thyroid (FNAB) processed by liquid-based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto-histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied. 150 cases of HT processed by conventional smear (CS) in 1996-98 and 670 with LBC in 2005-2007,were included. The majority of FNAB were carried out under USguidance and fixed with ethyl alcohol for the CS. LBC material was rinsed in the Cytolit solution, processed according to the manufacturer's recommendations. Among the 150 CS, 83 were HT while 67 were HN in HT; in the second triennium 245 LBC were HT and 425 were HN in HT. In the first period a follow-up (including a second FNA or surgery) was done in 92 cases, in the second period in 116. In the surgical group 97.1% in the first period were benign (all HT and 34/36 HN) and 2.8% malignant(all HN). In 2005-2007, 94% were benign (15 HT and 45/49 HN) and 6%malignant. Thirty HN from the second triennium had ICC for HBME-1 and Galectin-3 resulting negative in 93.5%. Among these cases, 10 had a benign histology and a concordant negative ICC. LBC can be used as a valid method for HT, especially for the possible application of ICC to HN, and it allows a correct preoperative selection of lesions, (Copyright © 2011 Wiley-Liss, Inc.)

In this study, we investigated the prognostic value of metastasis tumor antigen 1 expression in 81 untreated patients with ovarian cancer. The expression of metastasis tumor antigen 1 was evaluated by immunohistochemistry, and staining was analyzed in relation to clinicopathologic variables, disease-free survival, and overall survival. High expression of metastasis tumor antigen 1 was found to be associated with advanced stage (I/II versus III/IV, P = .02) and with worse response to first-line treatment (P = .03). Cases with high metastasis tumor antigen 1 expression showed a lower disease-free survival compared with cases with low expression (P = .02). In multivariate analysis of disease-free survival, metastasis tumor antigen 1 overexpression retained an independent negative prognostic role (P = .04), when considered together with histotype, stage of disease, residual tumor at surgery, and chemosensitivity. The evaluation of the prognostic relevance of metastasis tumor antigen 1 in late-stage disease showed that overexpression was a prognostic factor for poor disease-free survival and overall survival in this subset of patients, in both univariate and multivariate models. These findings indicate that metastasis tumor antigen 1 overexpression can be used as a predictor of clinical outcome in patients with ovarian cancer and therefore may represent a new prognostic marker., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Metastases to endometrium are a rare event. A case of a 53-year-old woman with a previous colon cancer presenting with a dysfunctional uterine bleeding is reported. The curettage specimens consisted of multiple fragments of proliferative endometrial tissue mixed with irregular glands, focally amputated, lined by very cells with elongated, hyperchromatic nuclei and solid sheets of neoplastic cells often filled with necrotic debris and inflammatory cells, resembling endometrioid adenocarcinoma. Neoplastic cells resulted positive at immunohistochemical reaction for CK20, CDX2, p53 and negative for CK7, vimentin, ER, and PR suggesting a metastatic colon adenocarcinoma. Absence of premalignant changes, such as hyperplasia, besides frankly malignant glands in an endometrial curette should be regarded as an alarming feature for a secondary nature mostly from large bowel. In these cases clinical history is crucial and an immunohistochemical panel made up of CK7, CK20, CDX2, p53, vimentin, ER, and PR is useful for the correct diagnosis.

This study was aimed at determining whether high-grade endometrioid carcinomas (grade 3 International Federation of Gynecology and Obstetrics) might overlap, at least partially, non-endometrioid carcinomas (type II). To this end, a panel of clinical-pathological and immunohistochemical parameters was evaluated in three different populations: low-grade endometrioid carcinomas (LGECs; n = 57), high-grade endometrioid carcinomas (HGECs; n = 26), and non-endometrioid carcinomas (NECs; n = 30). Besides morphological appearance, HGECs appeared similar to LGECs in p53 immunostaining profile; features different from LGECs included a higher local aggressiveness, a higher invasion of lymph-vascular spaces, a lower expression of ERalpha and PR, and a higher proliferative index. HGECs were similar to NECs for local aggressiveness, invasion rate of lymph-vascular spaces, lymph node metastasis incidence, and proliferative index. HGECs, however, showed a lower rate of extra-nodal metastases, a lower incidence of p53 overexpression, and a higher positivity for ERalpha and PR. In conclusion, results from this study show that HGECs exhibit overlapping morphological and immunohistochemical features of both type I and type II endometrial carcinomas. Further research is needed to clarify the clinical value of this observation.

Objective: To determine whether the ratio of hepatocyte growth factor (HGF) to transforming growth factor beta1 (TGFbeta1) in systemic lupus erythematosus (SLE) nephritis could be a prognostic factor for response to therapy with cyclophosphamide (CYC) and steroids at 6 months, and to examine whether the molecular ratio of HGF to TGFbeta1 correlates with the activity index (AI) and chronicity index (CI) and has predictive value for remission at the sixth month., Methods: Thirty-six SLE patients with new-onset nephritis, 25 of whom were treated with CYC and steroids, entered into a prospective observational cohort trial at a tertiary university referral center. Renal biopsy findings and clinical parameters were recorded for all patients. Histopathologic, clinical, and immunohistochemical data at baseline served to define the predictive value for the outcome at 6 months., Results: AI and CI at baseline did not distinguish patients who had achieved remission from those who had not achieved remission after receiving CYC plus steroids. HGF and TGFbeta1 were expressed in the tubuli, not in the glomeruli. The CI correlated directly with the TGFbeta1 extension score (TGFbeta1-ES) (r = 0.43, P = 0.008), but correlated indirectly with the HGF intensity score (HGF-IS) (r = -0.39, P = 0.02) and the HGF-ES (r = -0.45, P = 0.006). An HGF-ES:TGFbeta1-ES ratio of >or=1 at baseline distinguished patients who had achieved remission from those who had not achieved remission, with a predictive value of 94%., Conclusion: These findings indicate that baseline expression of renal HGF and TGFbeta1 predicts short-term renal outcome after therapy with CYC and steroids.

Esophageal carcinomas are steadily rising worldwide; they rank sixth among tumors. Adenocarcinoma is the most common histological type in Western countries while squamous carcinoma is more common in the developing countries. Both types are preceded by pre-neoplastic lesions rappresented by Barrett's esophagus for adenocarcinoma and low and high grade dysplasia for squamous carcinoma. Some continuity exists between dysplastic lesions and frankly invasive tumors. Moreover rare hystological types have been described. The surgical pathologist plays an important role in evaluating small endoscopic biopsies as well as in examining surgical specimens from esophagectomy. In the former case the role is exclusively diagnostic while in the latter surgical radicality, cancer stage and outcomes of neoadjuvant therapies are assessed. All these data are crucial not only for prognosis but also for therapy planning.