A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

Rabdomiosarcoma embrionario botrioide de útero / Embryonal botryoid rhabdomyosarcoma of the uterus

Resumen El rabdomiosarcoma es una neoplasia maligna de origen mesenquimal con diferenciación muscular estriada esquelética. Es el sarcoma más común de la infancia y presenta cuatro subtipos: embrio nario, alveolar, pleomórfico y de células ahusadas/esclerosante. De todos ellos el embrionario es el de mayor prevalencia y presenta una variante, botrioide, que suele comprometer órganos huecos en forma de una masa polipoide multilobulada. Presentamos el caso de una mujer de 27 años que consultó por sangrado vaginal y en quien se evidenció en la colposcopia, una lesión polipoide blanquecina que se exteriorizaba a través del orificio cervical externo. El estudio histológico reveló sectores celulares alternados por áreas laxas, mixoides, junto a glándulas ístmico-endometriales típicas. La proliferación fusocelular atípica, se disponía en nidos, constituidos por células de amplio citoplasma eosinófilo con estriaciones citoplasmáticas transversales y núcleos excéntricos con cromatina homogénea. Se exhibían áreas de células densamente condensadas inmediatas y próximas al revestimiento epitelial intacto, pero separadas de él, por una fina capa de estroma laxo (capa cambial). El perfil de inmunomarcación resultó positivo para desmina, actina músculo específico y miogenina, y negativo para actina músculo liso. Se realizó diagnóstico de rabdomiosarcoma embrionario botroide de cuerpo uterino.

Abstract Rhabdomyosarcoma is a malignant neoplasm of mesenchymal origin with skeletal striated mus cular differentiation. It is the most common sarcoma of childhood and has four subtypes: embryonal, alveolar, pleomorphic and spindle cell/sclerosing. Of all of them, the embryonal one is the most prevalent and presents a variant, botryoid, which usually involves hollow organs in the form of a multilobed polypoid mass. We pres ent the case of a 27-year-old woman who consulted for vaginal bleeding and in whom colposcopy revealed a whitish polypoid lesion that was externalized through the external cervical os. Histological examination revealed cellular sectors alternated by lax, myxoid areas, together with typical isthmic-endometrial glands. The atypical spindle cell proliferation was arranged in nests, made up of ce lls with large eosinophilic cytoplasm with transverse cytoplasmic striations and eccentric nuclei with homogeneous chromatin. Areas of densely packed cells were exhibited immediately, but separated from, the intact epithelial lining by a thin layer of loose stroma (cambium layer). The immunostaining profile was positive for desmin, muscle-specific actin and myogenin, and negative for smooth muscle actin. A diagnosis of embryonal botryoid rhabdomyosarcoma of the uterine corpus was made.

LHX1 as a potential biomarker regulates EMT induction and cellular behaviors in uterine corpus endometrial carcinoma

Abstract Objectives: To investigate the expression of LHX1 and its role as a biomarker in the diagnosis and prognosis of Uterine Corpus Endometrial Carcinoma (UCEC). Methods: The Cancer Genome Atlas (TCGA) database was used to detect the expression level of LHX1 in UCEC cells and tissues, and to find out the effect of LHX1 on prognosis. Co-expressed genes were then identified by Spearman correlation analysis, and the protein-protein interaction network was constructed using Cytoscape software. The R "clusterProfiler" package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A series of in vitro experiments were performed to evaluate LHX1 expression and detect UCEC cell proliferation, invasion, and migration. Western blotting was used to determine the effect of LHX1 on expression levels of Epithelial-Mesenchymal Transition (EMT)-related proteins. Results: LHX1 was upregulated in UCEC tissues and correlated with poor overall survival and disease-specific survival outcomes. Functional enrichment analysis suggested that genes co-expressed with LHX1 were enriched in cell adhesion. The expression of LHX1 was positively correlated with the expression levels of genes related to EMT induction and invasion. LHX1 can enhance the proliferation, migration, and invasion activities of UCEC cells in vitro, and alter the expression levels of EMT-related proteins. Conclusion: LHX1 expression was highly upregulated in UCEC cells and tissues, which was correlated with the prognosis of patients with UCEC. LHX1 may regulate UCEC progression at least in part by modulating EMT induction.

Dysregulation of MAD2L1/CAMK2A/PTTG1 Gene Cluster Maintains the Stemness Characteristics of Uterine Corpus Endometrial Carcinoma / 中国医学科学院学报

Objective To study the stemness characteristics of uterine corpus endometrial carcinoma(UCEC)and its potential regulatory mechanism.Methods Transcriptome sequencing data of UCEC was obtained from The Cancer Genome Atlas.Gene expression profile was normalized by edgeR package in R3.5.1.A one-class logistic regression machine learning algorithm was employed to calculated the mRNA stemness index(mRNAsi)of each UCEC sample.Then,the prognostic significance of mRNAsi and candidate genes was evaluated by survminer and survival packages.The high-frequency sub-pathways mining approach(HiFreSP)was used to identify the prognosis-related sub-pathways enriched with differentially expressed genes(DEGs).Subsequently,a gene co-expression network was constructed using WGCNA package,and the key gene modules were analyzed.The clusterProfiler package was adopted to the function annotation of the modules highly correlated with mRNAsi.Finally,the Human Protein Atlas(HPA)was retrieved for immunohistochemical validation.Results The mRNAsi of UCEC samples was significantly higher than that of normal tissues(

Study of malignant tumours of the uterine corpus: histopathology and immunohistochemistry

Background: The uterine corpus represents the second most common site for malignancy in the female genital tract. This study was performed to ascertain the profile of malignant tumours of the uterine corpus reported at our centre.Methods: A retrospective analysis of cases retrieved from the archives of the department of pathology from January 2014 to December 2016. Clinical information of the patients was collected from the hospital records.  Classification and grading of the tumours were done according to the current WHO classification.Results: Nineteen cases were studied. There were ten cases of endometrial adenocarcinoma, five cases of leiomyosarcoma, three cases of endometrial stromal sarcoma and one case of carcinosarcoma(malignant mixed mullerian tumour). The age range of endometrial adenocarcinoma was 55 to 85 years and presented with post menopausal bleeding, whereas endometrial stromal sarcomas occurred in women above 45 years of age. Leiomyosarcomas had age range from 26 to 65 years. All leiomyosarcomas were clinically diagnosed as fibroid. Majority of endometrial adenocarcinomas were well differentiated endometroid type. Out of the three endometrial stromal sarcomas two were high grade, one with metastasis. All leiomyosarcomas showed mitotic rate above 10/10hpf.Conclusions: Endometrial carcinomas form the majority of malignant tumours of uterine corpus and occur in older age group followed by leiomyosarcomas. Endometrial stromal sarcomas are less common and occur in middle aged and older patients. Leiomyosarcomas and stromal sarcomas are usually misdiagnosed as fibroids clinically unless metastases are present.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement / 부인종양

Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement.

An Unusual Relapse of Acute Lymphoblastic Leukemia in the Uterine Corpus / 대한산부인과학회잡지

The relapse of leukemia is usually classified as hematologic relapse and extramedullary relapse. The most common sites of clinical extramedullary relapse are the central nervous systems (CNS) and gonads. However, the relapse in the uterus is very rare. We experienced a very unusual case of uterine relapse of acute lymphoblastic leukemia (ALL) after about a 6-year remission period. This female patient returned to our hospital with a two-month history of amenorrhea. Pelvic radiology confirmed an about 7 cm sized ill-defined ovoid mass in the uterus. There was no evidence of ALL relapse in the peripheral blood or CNS. The uterine biopsy showed diffused homogenous infiltration of numerous small round cells in uterine corpus, suggesting ALL relapse. The bone marrow study revealed 100% cellularity, most of which were lymphoblasts. Our patient received the bone marrow transplantation (BMT) and achieved the second complete remission (CR). Therefore, we here report our case with a brief review of literature.