Genomic profile in gestational and non-gestational choriocarcinomas.

INTRODUCTION: Gestational (GC) (derived from the placenta) and non-gestational (NGC) choriocarcinomas are trophoblastic diseases originated from abnormal proliferation of trophoblastic cells. These rare tumors share similar morphology and pathological features and differ on chemotherapy response, genetic origin and prognosis. In this study, the genomic profile of choriocarcinomas was performed according to their origin (GC or NGC) aiming to better understand these poorly characterized diseases. METHODS: Thirteen patients were included in this study; 10 presented previous history of hydatidiform mole and six developed metastasis. Twelve polymorphic microsatellite markers (D15S659, APOC2, D5S816, BAT25, D3S1614, D3S1311, D1S1656, APC-D5S346, D3S1601, D18S70, D8S1110 and D11S1999) were investigated to distinguish GC from NGC. All choriocarcinomas were evaluated by copy number alterations using array CGH. RESULTS: Eight cases were classified as GC and five as NGC. Although potentially polymorphic, NGC exhibited significant gain of 21p11. Rare copy number alterations (CNA) were detected as a frequent event in GC including gains of 1p36.33-p36.32 (3 cases), 17q25.3 (4 cases), and losses of 9q33.1 (5 cases), 17q21.3 (3 cases) and 18q22.1 (4 cases) (varying from 724 to 3,053 Kb). DISCUSSION: Two tumor suppressor genes are candidates to be involved in GC: TRIM32 (9q33.1) and CDH19 (18q22.1). Gains of CBX2, CBX4 and CBX8 were frequently found in high risk prognostic score in GC. The in silico functional interaction analysis revealed the involvement of PTEN and PI3K-Akt signaling pathways. These data pointed out significant genomic alterations in GC, opening new avenues to better characterize the pathobiology of this disease.

Apoptotic index for prediction of postmolar gestational trophoblastic neoplasia.

BACKGROUND: Although 85% of patients with a complete hydatidiform mole achieve spontaneous remission after a few months, 15% of them will experience gestational trophoblastic neoplasia, which requires chemotherapy. To date, there is no biomarker to predict post-molar gestational trophoblastic neoplasia before the initiation of human chorionic gonadotropin surveillance. OBJECTIVE: The purpose of this study was to assess the relationship between the expression of apoptosis markers in the molar villous trophoblasts and the subsequent development of gestational trophoblastic neoplasia after the evacuation of a complete hydatidiform mole. STUDY DESIGN: This was a retrospective cohort study of patients with complete hydatidiform mole who were diagnosed, treated, and followed at the Center of Trophoblastic Diseases (Botucatu/São Paulo State and Rio de Janeiro/Rio de Janeiro State, Brazil) from 1995-2014. Patients were divided temporally into derivation (1995-2004) and validation (2005-2014) cohorts. Immunohistochemistry was used to examine tissue expression of the apoptosis inhibitor survivin or the pro-apoptotic enzyme caspase-3. Survivin stains for cytoplasmic and nuclear expression were evaluated independently. Caspase-3 expression was measured as an apoptotic index of positive staining cells over negative staining cells multiplied by 100. Receiver operating characteristic curves were then constructed, and the area under the curve was calculated to test the performance characteristics of the staining to predict the subsequent development of gestational trophoblastic neoplasia. RESULTS: The final study population comprised 780 patients, with 390 patients in each temporal cohort: 590 patients entered spontaneous remission, and 190 patients experienced post-molar gestational trophoblastic neoplasia. Neither nuclear nor cytoplasmic survivin expression performed well as a predictor of subsequent gestational trophoblastic neoplasia. The caspase-3 apoptotic index was a strong risk factor for subsequent gestational trophoblastic neoplasia development. When the apoptotic index was <4%, the risk of gestational trophoblastic neoplasia had an odds ratio of 35.55 (95% confidence interval, 14.02-90.14; P < .0001) in the derivation cohort and an odds ratio of 25.71 (95% confidence interval, 10.13-65.29; P < .0001) in the validation cohort. However, in both cohorts, the positive predictive value for gestational trophoblastic neoplasia of an apoptotic index <4.0% was modest (49% in the derivation cohort and 41% in the validation cohort); the negative predictive value for gestational trophoblastic neoplasia of an apoptotic index ≥4.0% was high (97% in both cohorts). CONCLUSION: The subsequent development of gestational trophoblastic neoplasia after evacuation of complete hydatidiform mole is tied closely to the apoptotic index, which may be a useful biomarker for future prospective studies.

Usefulness of clinical, ultrasonographic, hysteroscopic, and immunohistochemical parameters in differentiating endometrial polyps from endometrial cancer.

STUDY OBJECTIVE: To evaluate the usefulness of clinical, ultrasonographic, hysteroscopic, and immunohistochemical parameters in differentiating endometrial polyps from endometrial cancer. DESIGN: Cross-sectional study (Canadian Task Force classification II-2). SETTING: Tertiary public hospital, university teaching center. PATIENTS: Eighty-two women who underwent hysteroscopic polypectomy and 20 women who underwent surgery to treat endometrial cancer. INTERVENTIONS: Analysis of medical records and immunohistochemical assessment of estrogen receptors, progesterone receptors, and endothelial markers CD34 and CD105. MEASUREMENTS AND MAIN RESULTS: Among women with endometrial cancer and endometrial polyps, respectively, mean age was 63 and 57 years (p = .01), 89% and 67% were postmenopausal (p < .05), and 85% and 30.5% had postmenopausal bleeding (p < .01). No sonographic parameter enabled differentiation of endometrial polyp from cancer. Of patients with endometrial cancer, 72% exhibited signs suggestive of hyperplasia, and endometrial polyps were diagnosed during hysteroscopy. Estrogen receptors (≥ 2 vs ≥ 1; p < .001) and progesterone receptors (≥ 3 vs ≥ 2; p = .07) were greater in endometrial polyps. There was no significant difference in microvessel density (p > .05). CONCLUSIONS: Ultrasonographic parameters and endothelial markers did not enable differentiation of polyps from endometrial neoplasia. Postmenopausal bleeding and endometrial hypervascularization along with vascular atypia at diagnostic hysteroscopy showed a greater association with endometrial cancer.

Post-Ganglionic Horner's Syndrome: An Unusual Presentation of Non-Hodgkin Lymphoma.

In this paper, we present the rare case of a patient with cervical lymphadenopathy diagnosed as a T-cell-rich B-cell non-Hodgkin lymphoma that manifested Horner's syndrome due to a post-ganglionic sympathetic neuron lesion caused by the tumor.

Tumor microenvironmental genomic alterations in juvenile nasopharyngeal angiofibroma.

BACKGROUND: To better characterize the pathophysiology of juvenile nasopharyngeal angiofibroma (JNA), endothelial and stromal cells were evaluated by genomic imbalances in association with transcript expression levels of genes mapped on these altered regions. METHODS: High-resolution comparative genomic hybridization (HR-CGH) was used in laser-captured endothelial and stromal cells from 9 JNAs. Ten genes were evaluated by quantitative real-timereverse transcription polymerase chain reaction (qRT-PCR) in 15 cases. RESULTS: Although gains were more frequently detected in endothelial cells, 57% of chromosomal alterations were common by both components. Gene expression analyses revealed a positive correlation between endothelial and stromal components for ASPM, CDH1, CTNNB1, FGF18, and SUPT16H. A significant difference was found for FGF18 and AURKB overexpression in stromal cells and AR down-expression in endothelial cells. CONCLUSIONS: A similar pattern of gene expression and chromosomal imbalances in both exponents would suggest a common mechanism of functional regulation. AURKB, FGF18, and SUPT16H were identified as potential molecular markers in JNA.

Carcinoma de nasofaringe: análise da importância prognóstica da imunoexpressão da galectina-3 e proteínas de matriz / Nasopharynx Carcinoma: Analyse of the prognostic importance of the immunoexpression of galactin-3 and matrix proteins

Objetivo: Estudar a expressão da Galectina-3 e a distribuiçãodas proteínas de matriz, laminina, fibronectina e colágeno IV,em 30 amostras teciduais de carcinoma de nasofaringe (CNF)e correlacionar com as características clinicopatológicas,agressividade tumoral e sobrevida dos indivíduos. Forma deestudo: clínico retrospectivo. Material: Foram estudadas pormétodo imunohistoquímico a expressão das proteínas de matrize a galectina-3 de 30 amostras teciduais de 26 pacientes comdiagnóstico de Carcinoma de Nasofaringe. Resultados: A análisemostrou que a media etária foi de 48 anos, com o pico de prevalênciaentre 60 a 69 anos, e predominância do sexo masculino de 2:1. OCarcinoma Escamoso Não Ceratinizante Indiferenciado foi maiscomum em 23 amostras (76,7%), o Carcinoma Escamoso NãoCeratinizante Diferenciado em 4 amostras (13.3%) e CarcinomaEscamoso Ceratinizante em 3 amostras (10,0%). A expressãoda laminina que normalmente é restrita à parede dos vasos e nalâmina própria, estava muito aumentada na matriz das célulasneoplásicas em 23 amostras (76,7%); a fibronectina foi positivaem 13 amostras (43%) e a galectina-3 foi positiva em 21 amostras(70%). Tivemos correlação positiva da laminina, fibronectina egalectina-3 em 7 amostras (23,3%) e entre laminina e galectina-3em 11amostras (36,6%). Conclusão: A expressão positiva daGalectina-3 e da laminina não mostrou correlação significativaquanto à agressividade tumoral e a sobrevida dos pacientes,enquanto a expressão da fibronectina está associada a menortaxas de recidiva tumoral.

Vocal fold nodules: morphological and immunohistochemical investigations.

The objective of this study was to investigate the morphological and immunohistochemical characteristics of vocal fold nodules. The study design was prospective and retrospective. For the histological study, we reviewed 15 slides from the surgical cases of vocal fold nodules, in which we analyzed epithelium, basal membrane (bm), and lamina propria. For the transmission and scanning electron microscopy (TEM, SEM) studies, five new cases on vocal fold nodules were included. Immunohistochemistry study was carried out in the 15 specimens, using antifibronectin, antilaminin, and anticollagen IV antibodies. The main histological alterations were epithelial hyperplasia (73.33%), basement membrane thickening (86.66%), edema, and fibrosis (93.33%). SEM--reduction in mucous lacing and increase in the desquamating cells, without epithelial erosion. TEM--hyperplasia of the epithelium, enlargement of the intercellular junctions, which was filled by fluid, subepithelial thickening of the lamina reticularis, and break points in the basal membrane. Immunohistochemistry--we identified greater immunoexpression of fibronectin on the basal membrane, on the lamina propria, and around the vessels. Antilaminin and anticollagen IV antibodies showed higher pigmentation on the endothelium of the vessels than that on the basal membrane. In vocal fold nodules, combined assessment using light microscopy, electron microscopy, and immunohistochemistry can reveal important morphological details useful in characterizing these lesions.

Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor.

Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs.