Detection of high mobility group A2 specific mRNA in the plasma of patients affected by epithelial ovarian cancer

Ovarian cancer is the most lethal gynecological malignancy and the high mortality rate is associated with advanced-stage disease at the time of the diagnosis. In order to find new tools to make diagnosis of Epithelial Ovarian Cancer (EOC) at early stages we have analyzed the presence of specific HMGA2 mRNA in the plasma of patients affected by this neoplasm. HMGA2 overexpression represents a feature of several malignances including ovarian carcinomas. Notably, we detected HMGA2 specific mRNA in the plasma of 40 out 47 patients with EOC, but not in the plasma of healthy donors. All cases found positive for HMGA2 mRNA in the plasma showed HMGA2 protein expression in EOC tissues. Therefore, on the basis of these results, the analysis of circulating HMGA2 specific mRNA might be considered a very promising tool for the early diagnosis of EOC

TLR4 expression in ex-Lichenoid lesions—oral squamous cell carcinomas and its surrounding epithelium: the role of tumor inflammatory microenvironment

Abstract: Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immuno histochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex–OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development

Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22)

BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine (R)).RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found.CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics

PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration

PATZ1, a POZ-Zinc finger protein, is emerging as an important regulator of development and cancer, but its cancer-related function as oncogene or tumor-suppressor is still debated. Here, we investigated its possible role in thyroid carcinogenesis. We demonstrated PATZ1 is down-regulated in thyroid carcinomas compared to normal thyroid tissues, with an inverse correlation to the degree of cell differentiation. In fact, PATZ1 expression was significantly further down-regulated in poorly differentiated and anaplastic thyroid cancers compared to the papillary histotype, and it resulted increasingly delocalized from the nucleus to the cytoplasm proceeding from differentiated to undifferentiated thyroid carcinomas. Restoration of PATZ1 expression in three thyroid cancer-derived cell lines, all characterized by fully dedifferentiated cells, significantly inhibited their malignant behaviors, including in vitro proliferation, anchorage-independent growth, migration and invasion, as well as in vivo tumor growth. Consistent with recent studies showing a role for PATZ1 in the p53 pathway, we showed that ectopic expression of PATZ1 in thyroid cancer cells activates p53-dependent pathways opposing epithelial-mesenchymal transition and cell migration to prevent invasiveness. These results provide insights into a potential tumor-suppressor role of PATZ1 in thyroid cancer progression, and thus may have potential clinical relevance for the prognosis and therapy of thyroid cancer

Axillary node metastasis from differentiated thyroid carcinoma with hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings

<p>Abstract</p> <p>Background</p> <p>Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis.</p> <p>Case presentation</p> <p>Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hürthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml.</p> <p>Discussion and Conclusion</p> <p>Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.</p

Emotional false memories in children with learning disabilities

Research has shown that children with learning disabilities (LD) are less prone to evince associative illusions of memory as a result of impairments in their ability to engage in semantic processing. However, it is unclear whether this observation is true for scripted life events, especially if they include emotional content, or across a broad spectrum of learning disabilities. The present study addressed these issues by assessing recognition memory for script-like information in children with nonverbal learning disability (NLD), children with dyslexia, and typically developing children (N=51). Participants viewed photographs about 8 common events (e.g., family dinner), and embedded in each episode was either a negative or a neutral consequence of an unseen action. Children\u2019s memory was then tested on a yes/no recognition task that included old and new photographs. Results showed that the three groups performed similarly in recognizing target photographs, but exhibited differences in memory errors. Compared to other groups, children with NLD were more likely to falsely recognize photographs that depicted an unseen cause of an emotional seen event and associated more \u201cRemember\u201d responses to these errors. Children with dyslexia were equally likely to falsely recognize both unseen causes of seen photographs and photographs generally consistent with the script, whereas the other participant groups were more likely to falsely recognize unseen causes rather than script-consistent distractors. Results are interpreted in terms of mechanisms underlying false memories\u2019 formation in different clinical populations of children with LD

Lung cancer diagnosis on ovary mass: A case report

Metastatic neoplasms to the ovary often cause diagnostic problems, in particular those large ovarian masses mimicking primary tumors. Most of these tumors arise from digestive system or breast, while 37-year-old woman diagnosed as right adnexal complex mass, with a subpleural nodule in the apical part of the left lower lobe, at preoperative chest computed tomography scan. The patient underwent total abdominal hysterectomy with right salpingo-oophorectomy (ovarian mass 220 × 200 mm), total omentectomy, left ovarian biopsy, peritoneal random biopsies, and peritoneal washings for cytology. Pathologic and immunohistochemical examination of ovarian specimen suggested morphology and expression of metastatic lung adenocarcinoma with an intense positivity for Thyroid Transcriptional Factor-1 (TTF-1) and Cytokeratin 7 (CK7) staining. Fine needle biopsy of the lung nodule found epithelioid like malignant cells, confirming the diagnosis of an ovarian metastasis from a primary lung cancer. This report focused on the clinical and pathologic diagnostic challenge of distinguishing secondary from primary ovarian neoplasms. Issues on useful immunohistochemical stains are also discussed

Massive edema of ovary with cytogenetic alteration of chromosome 12q13-15 in adolescent patient: A case report

BACKGROUND: The massive edema of ovary, with or without fibromatosis, is a rare tumor-like entity characterized by an increase in volume of one or both ovaries for accumulation of edema fluid in the stroma that separates the follicular structures. CASE: We report a rare case, very peculiar also for its association with a massive stromal fibromatosis and for the presence, never described, of tumoral areas with CHOP gene translocation, on chromosome 12q13–15

Adhesion molecules and p16 expression in endocervical adenocarcinoma

An immunohistochemical (IHC) study has been conducted on 34 cases of untreated endocervical adenocarcinomas collected among three institutions (Ospedale S. Andrea, Rome; Istituto Nazionale Tumori "Fondazione G. Pascale", Naples; and Clinica Malzoni, Avellino). The E-cadherin and alpha- and beta-catenin complex status has been investigated along with p16INK4a in all studied cases with the aim to study whether the pattern of expression of the cadherin-catenin complex could be causally related to the expression of P16INK4a protein. Results were evaluated for statistical significance by a non-parametric test (Kruskal-Wallis). Endocervical adenocarcinomas as a group were uniformly expressing p16INK4a except for two cases, and all lesions displayed downregulation of the cadherin-catenin complex, without demonstrating statistically significant differences among the different histotypes. The lack of nuclear accumulation of beta-catenin found in this group of lesions probably implies that no alteration of the beta-catenin/Wnt metabolic pathway is present in endocervical adenocarcinoma, as opposed to what is found in the literature for squamous carcinoma of the cervix. The diffuse expression of p16INK4a protein in this group of neoplasms stresses the important role of high-risk human papillomavirus infection in neoplastic causation possibly via the viral E7-mediated inactivation of pRB tumor-suppressor protein and also underlines the useful role of p16INK4a immunostaining in the diagnostic algorithm of endocervical adenocarcinomas. In consideration of these findings, investigation of downstream beta-catenin genes c-myc and cyclin D1 is sought as possibly contributive in the molecular pathogenesis of endocervical adenocarcinoma