A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer.

BACKGROUND: The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer. METHODS: A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes. RESULTS: The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%. CONCLUSION: We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.

Squamous differentiation portends poor prognosis in low and intermediate-risk endometrioid endometrial cancer.

BACKGROUND: Endometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer. METHODS: A case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging. RESULTS: Twenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031). CONCLUSION: Our data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence.

Establishment, molecular and biological characterization of HCB-514: a novel human cervical cancer cell line.

Cervical cancer is the fourth most common cancer in women. Although cure rates are high for early stage disease, clinical outcomes for advanced, metastatic, or recurrent disease remain poor. To change this panorama, a deeper understanding of cervical cancer biology and novel study models are needed. Immortalized human cancer cell lines such as HeLa constitute crucial scientific tools, but there are few other cervical cancer cell lines available, limiting our understanding of a disease known for its molecular heterogeneity. This study aimed to establish novel cervical cancer cell lines derived from Brazilian patients. We successfully established one (HCB-514) out of 35 cervical tumors biopsied. We confirmed the phenotype of HCB-514 by verifying its' epithelial and tumor origin through cytokeratins, EpCAM and p16 staining. It was also HPV-16 positive. Whole-exome sequencing (WES) showed relevant somatic mutations in several genes including BRCA2, TGFBR1 and IRX2. A copy number variation (CNV) analysis by nanostring and WES revealed amplification of genes mainly related to kinases proteins involved in proliferation, migration and cell differentiation, such as EGFR, PIK3CA, and MAPK7. Overexpression of EGFR was confirmed by phospho RTK-array and validated by western blot analysis. Furthermore, the HCB-514 cell line was sensitive to cisplatin. In summary, this novel Brazilian cervical cancer cell line exhibits relevant key molecular features and constitutes a new biological model for pre-clinical studies.

An unusual presentation of giant pilomatrixoma in an adult patient.

BACKGROUND: Pilomatrixoma (OMIM ID #132600) is a benign cutaneous tumor originating from the pilosebaceous follicle and characterized by the presence of subcutaneous nodules of up to 3.0 cm in diameter, usually on the head, neck and upper extremities. It is most common in the first two decades of life and after the age of 60. MAIN OBSERVATIONS: An adult female patient was evaluated, presenting a solid tumoral lesion with erythematous surface and purplish tone, with approximately 7.5 x 5.0 cm in size, in the interscapulovertebral region. It was thought to be an epidermoid cyst, sarcoma, calcified hemangioma, giant dermatofibroma, or nodular basal cell carcinoma. The resection of the lesion was carried out and, at the histological examination, specific details were observed that led to the diagnosis of pilomatrixoma. CONCLUSION: Pilomatrixoma should be suspected in the differential diagnosis of giant adnexal tumors.

Diagnostic accuracy of frozen section tests for surgical diseases.

OBJECTIVE: To evaluate the accuracy of frozen section tests at different anatomical sites performed in an academic department of pathology. METHODS: We conducted a retrospective study from a computerized database of all frozen section tests. These diagnoses were compared to definite paraffin, used as controls. The tests were divided into three groups: inconclusive, consistent and inconsistent, the latter being subdivided into false positives and false negatives. The main indications for examinations and anatomical sites involved with diagnostic disagreements were also analyzed. RESULTS: Four hundred and thirty-three specimens were frozen tested, and the main indication was diagnostic (75.75%). In 404 tests (93.30%) diagnoses of biopsies in paraffin and frozen section were consistent. In 20 cases (4.62%) the results of frozen section biopsy were inconclusive and in 9 (2.08%) they were false negative. There were no false positive results. The most commonly assessed organ was the thyroid (25.64%). In the overall analysis, the body region most related with inconclusive diagnoses was the thyroid (seven cases) and in relation to specific sites it was the lungs/pleura/mediastinum (13.33%). Skin was the organ that showed more discordant diagnoses between frozen biopsies and paraffin. CONCLUSION: The global accuracy of frozen section was 93.30%; for specific anatomical sites, diagnostic accuracy ranged from 86.67% to 100%.

Precisão diagnóstica das doenças cirúrgicas nos exames por congelação / Diagnostic accuracy of frozen section tests for surgical diseases

OBJETIVO: Avaliar o grau de precisão diagnóstica dos exames por congelação em diferentes sítios anatômicos realizados em um serviço universitário de patologia. MÉTODOS: Foi realizado estudo retrospectivo a partir de banco de dados informatizado de todos os exames por congelação. Estes diagnósticos foram comparados com os definitivos em parafina, utilizados como controles. Os exames foram distribuídos em três grupos: inconclusivos, concordantes e não concordantes, sendo este último subdivido em falsos positivos e falsos negativos. As principais indicações dos exames e os sítios anatômicos envolvidos com as divergências diagnósticas também foram analisados. RESULTADOS: Quatrocentas e trinta e três peças cirúrgicas foram submetidas a exames por congelação, sendo a principal indicação o diagnóstico da lesão (75,75 por cento). Em 404 exames (93,30 por cento) os diagnósticos das biópsias por congelação e em parafina foram concordantes. Em 20 (4,62 por cento) casos os resultados das biópsias por congelação foram inconclusivos e em nove (2,08 por cento) ocorreram falsos negativos. Não houve resultados falsos positivos. O principal órgão avaliado foi a tireoide (25,64 por cento). Na análise global, a região do corpo mais relacionada com os diagnósticos inconclusivos por congelação foi a tireoide (sete casos) e em relação aos sítios específicos foram os pulmões/pleura/mediastino (13,33 por cento). Pele foi o órgão que mais apresentou diagnósticos discordantes entre biópsias por congelação e em parafina. CONCLUSÃO: A acurácia da congelação de forma global foi de 93,30 por cento; por sítios anatômicos específicos, a precisão diagnóstica variou de 86,67 por cento a 100 por cento.

OBJECTIVE: To evaluate the accuracy of frozen section tests at different anatomical sites performed in an academic department of pathology. METHODS: We conducted a retrospective study from a computerized database of all frozen section tests. These diagnoses were compared to definite paraffin, used as controls. The tests were divided into three groups: inconclusive, consistent and inconsistent, the latter being subdivided into false positives and false negatives. The main indications for examinations and anatomical sites involved with diagnostic disagreements were also analyzed. RESULTS: Four hundred and thirty-three specimens were frozen tested, and the main indication was diagnostic (75.75 percent). In 404 tests (93.30 percent) diagnoses of biopsies in paraffin and frozen section were consistent. In 20 cases (4.62 percent) the results of frozen section biopsy were inconclusive and in 9 (2.08 percent) they were false negative. There were no false positive results. The most commonly assessed organ was the thyroid (25.64 percent). In the overall analysis, the body region most related with inconclusive diagnoses was the thyroid (seven cases) and in relation to specific sites it was the lungs/pleura/mediastinum (13.33 percent). Skin was the organ that showed more discordant diagnoses between frozen biopsies and paraffin. CONCLUSION: The global accuracy of frozen section was 93.30 percent; for specific anatomical sites, diagnostic accuracy ranged from 86.67 percent to 100 percent.

Caracterização da doença pulmonar intersticial: um estudo de autópsia em crianças / Characterization of the intersticial lung disease: a children autopsy study

Até um terço dos óbitos em unidades de terapia intensiva estão associados à falência respiratória devido à falência respiratória à doença pulmonar exclusiva ou a falência respiratória de múltiplos órgãos. Doença pulmonar intersticial aguda (DPIA)/ dano alveolar difuso(DAD) é uma frequente apresentação histológica de falência respiratória de várias etiologias em crianças. /Up to one third of deaths in pediatric intensive car units or associated with respiratory failure due to pulmonary disease alone or multiorgan failure. Acute Interstitial Lung Disease (AILD) Diffuse Alveolar Damage (DAD) is a frequent histological presentation of respiratory...