Endometrial Tumor Classification by Histomorphology and Biomarkers in the Nurses’ Health Study

Objective. Endometrial cancers have historically been classified by histomorphologic appearance, which is subject to interobserver disagreement. As molecular and biomarker testing has become increasingly available, the prognostic significance and accuracy of histomorphologic diagnoses have been questioned. To address these issues for a large, prospective cohort study, we provide the results of a centralized pathology review and biomarker analysis of all incidental endometrial carcinomas occurring between 1976 and 2012 in the Nurses’ Health Study. Methods. Routine histology of all ( n = 360 ) cases was reviewed for histomorphologic diagnosis. Cases were subsequently planted in a tissue microarray to explore expression of a variety of biomarkers (e.g., ER, PR, p53, PTEN, PAX2, AMACR, HNF1β, Napsin A, p16, PAX8, and GATA3). Results. Histologic subtypes included endometrioid (87.2%), serous (5.6%), carcinosarcoma (3.9%), clear cell (1.7%), and mixed type (1.7%). Biomarker results within histologic subtypes were consistent with existing literature: abnormal p53 was frequent in serous cases (74%), and HNF1β (67%), Napsin A (67%), and AMACR (83%) expression was frequent in clear cell carcinomas. Our dataset also allowed for examination of biomarker expression across non-preselected histologies. The results demonstrated that (1) HNF1β was not specific for clear cell carcinoma, (2) TP53 mutations occurred across many histologies, and (3) GATA3 was expressed across multiple histotypes, with 75% of positive cases demonstrating high-grade features. Conclusions. Our findings establish the subtypes of endometrial cancer occurring in the Nurses’ Health Study, corroborate the sensitivity of certain well-established biomarkers, and call into question previously identified associations between certain biomarkers (e.g., HNF1B) and particular histotypes.

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Prognostic significance of lymphocyte-to-monocyte ratio and CRP in patients with nonmetastatic clear cell renal cell carcinoma: a retrospective multicenter analysis

OncoTargets and Therapy ◽

10.2147/ott.s101458 ◽

2016 ◽

pp. 2759 ◽

Cited By ~ 1

Author(s):

Hong Hu ◽

Wen-Kai Xia ◽

Xia Wu ◽

Tang-Hong Yu ◽

Yu Wu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Prognostic Significance ◽

Cell Renal Cell Carcinoma ◽

Lymphocyte To Monocyte Ratio ◽

Multicenter Analysis

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Use of Circulating Tumour DNA (ctDNA) for Measurement of Therapy Predictive Biomarkers in Patients with Cancer

Journal of Personalized Medicine ◽

10.3390/jpm12010099 ◽

2022 ◽

Vol 12 (1) ◽

pp. 99

Author(s):

Michael J. Duffy ◽

John Crown

Keyword(s):

Gold Standard ◽

Kinase Inhibitors ◽

Predictive Biomarkers ◽

Lower Sensitivity ◽

Cancer Therapies ◽

Gold Standard Method ◽

Biomarker Analysis ◽

Egfr Tyrosine Kinase Inhibitors ◽

Biomarker Testing ◽

Circulating Tumour Dna

Biomarkers that predict likely response or resistance to specific therapies are critical in personalising treatment for cancer patients. Such biomarkers are now available for an increasing number of anti-cancer therapies, especially targeted therapy and immunotherapy. The gold-standard method for determining predictive biomarkers requires tumour tissue. Obtaining tissue, however, is not always possible and even if possible, the amount or quality of tissue obtained may be inadequate for biomarker analysis. Tumour DNA, however, can be released into the bloodstream, giving rise to what is referred to as circulating tumour DNA (ctDNA). In contrast to tissue, blood can be obtained from effectively all patients in a minimally invasive and safe manner. Other advantages of blood over tissue for biomarker testing include a shorter turn-around time and an ability to perform serial measurements. Furthermore, blood should provide a more complete profile of mutations present in heterogeneous tumours than a single-needle tissue biopsy. A limitation of blood vis-à-vis tissue, however, is lower sensitivity and, thus, the possibility of missing an actionable mutation. Despite this limitation, blood-based predictive biomarkers, such as mutant EGFR for predicting response to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer and mutant PIK3CA for predicting response to alpelisib in combination with fulvestrant in advanced breast cancer, may be used when tissue is unavailable. Although tissue remains the gold standard for detecting predictive biomarkers, it is likely that several further blood-based assays will soon be validated and used when tissue is unavailable or unsuitable for analysis.

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A Mitochondrial Dysfunction and Oxidative Stress Pathway-Based Prognostic Signature for Clear Cell Renal Cell Carcinoma

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9939331 ◽

2021 ◽

Vol 2021 ◽

pp. 1-32

Author(s):

Yue Wu ◽

Xi Zhang ◽

Xian Wei ◽

Huan Feng ◽

Bintao Hu ◽

...

Keyword(s):

Oxidative Stress ◽

Renal Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Risk Group ◽

Prognostic Significance ◽

Individual Risk ◽

Cell Renal Cell Carcinoma

Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, P = 0.008 ). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.

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Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Life ◽

10.3390/life11101047 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1047

Author(s):

Justin Z. Amarin ◽

Razan Mansour ◽

Sura Al-Ghnimat ◽

Maysa Al-Hussaini

Keyword(s):

Overall Survival ◽

Tumor Cells ◽

Chart Review ◽

Prognostic Significance ◽

Retrospective Chart Review ◽

Cancer Center ◽

High Grade ◽

Endometrial Carcinomas

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.

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Identification of Tumor Microenvironment-Related Genes in Kidney Renal Clear Cell Carcinoma Patients via Bioinformatic Analysis

10.21203/rs.3.rs-471905/v1 ◽

2021 ◽

Author(s):

Rongjiong Zheng ◽

Yaosen SHao ◽

Mingming Wang ◽

Yeli Tang ◽

Meiling Hu

Keyword(s):

Tumor Microenvironment ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Expression Profiles ◽

Prognostic Significance ◽

Enrichment Analysis ◽

Renal Clear Cell Carcinoma ◽

The Cancer Genome Atlas ◽

Functional Enrichment

Abstract BackgroundTumor microenvironment has been implicated in the development and progression of cancers. However, the prognostic significance of tumor microenvironment-related genes in kidney renal clear cell carcinoma (KIRC) remains unclear. MethodsIn this study, we obtained and analyzed gene expression profiles from The Cancer Genome Atlas database. Stromal and immune scores were calculated based on the ESTIMATE algorithm. ResultsIn the discovery series of 537 patients, we identified a list of differentially expressed genes which was significantly associated with prognosis in KIRC patients. Protein-protein interaction networks and functional enrichment analysis were both performed, indicating that these identified genes were related to the immune response. ConclusionsThe tumor microenvironment-related genes could serve as the potential biomarkers for KIRC.

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Prognostic significance of hypoxia inducible factor-1α expression in patients with clear cell renal cell carcinoma

Molecular Medicine Reports ◽

10.3892/mmr.2018.8409 ◽

2018 ◽

Cited By ~ 2

Author(s):

Shuiqing Wu ◽

Fen Jiang ◽

Hongtao Wu ◽

Yinhuai Wang ◽

Ran Xu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Hypoxia Inducible Factor ◽

Prognostic Significance ◽

Cell Renal Cell Carcinoma ◽

Hypoxia Inducible Factor 1Α

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MSX1—A Potential Marker for Uterus-Preserving Therapy of Endometrial Carcinomas

International Journal of Molecular Sciences ◽

10.3390/ijms21124529 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4529

Author(s):

Simon Eppich ◽

Christina Kuhn ◽

Elisa Schmoeckel ◽

Doris Mayr ◽

Sven Mahner ◽

...

Keyword(s):

Clear Cell ◽

Steroid Receptors ◽

Inhibitory Effect ◽

Ovarian Carcinomas ◽

Term Survival ◽

Potential Marker ◽

Potential Factor ◽

Tumor Material ◽

Endometrial Carcinomas

Prognostic factors are of great interest in patients with endometrial cancer. One potential factor could be the protein MSX1, a transcription repressor, that has an inhibitory effect on the cell cycle. For this study, endometrioid endometrial carcinomas (n = 53), clear cell endometrial carcinomas (n = 6), endometrioid ovarian carcinomas (n = 19), and clear cell ovarian carcinomas (n = 11) were immunochemically stained for the protein MSX1 and evaluated using the immunoreactive score (IRS). A significant stronger expression of MSX1 was found in endometrioid endometrial carcinomas (p < 0.001), in grading 2 (moderate differentiation) (p = 0.001), and in tumor material of patients with no involvement of lymph nodes (p = 0.031). Correlations were found between MSX1 expression and the expression of β-Catenin, p21, p53, and the steroid receptors ERα, ERβ, PRα, and PRβ. A significant (p = 0.023) better survival for patients with an MSX1 expression in more than 10% of the tumor cells was observed for endometrioid endometrial carcinomas (21.3 years median survival (MSX1-positive) versus 17.3 years (MSX1-negative)). Although there is evidence that MSX1 expression correlates with improved long-term survival, further studies are necessary to evaluate if MSX1 can be used as a prognostic marker.

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PD-L1/PD-1 Expression in Endometrial Clear Cell Carcinoma: A Potential Surrogate Marker for Clinical Trials

International Journal of Surgical Pathology ◽

10.1177/1066896919862618 ◽

2019 ◽

Vol 28 (1) ◽

pp. 31-37

Author(s):

Cao Jin ◽

Sean Hacking ◽

Sharon Liang ◽

Mansoor Nasim

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Surrogate Marker ◽

Myometrial Invasion ◽

Lymphocyte Infiltration ◽

Pathological Features ◽

Napsin A ◽

Programmed Death ◽

Clinical And Pathological Features

Background. Endometrial clear cell carcinoma (ECCC) represents a rare subtype of endometrial cancer. Recently, immunotherapeutic drugs targeting programmed cell death protein 1 (PD-1)/programmed death ligand-1 (PD-L1) was associated with improved survival in several types of cancer (especially in patients with mismatch-repair (MMR)-deficient status). The aim of this study is to evaluate the correlation between the PD-L1/PD-1 axis and clinical and pathological features in strictly defined ECCC diagnosed at our institution. Design. Review of ECCC (diagnosed in the period of 2000 to 2017) identified 23 cases (n = 23) in our institution. The cases were reviewed by 2 gynecological pathologists. Estrogen receptor, progesterone receptor, napsin A, p16, and p53 were also performed so that only pure CCC cases were included. PD-L1 (SP142), PD-1, and MMR antibodies were performed. PD-L1 and PD-1 were scored in both the tumor and the peritumoral lymphocyte infiltration. Clinical and pathological features were recorded to correlate with the expression of the 2 markers. Results. Among the 23 cases, 20 cases were qualified for pure CCC by histology and immunohistochemistry patterns. Regarding PD-1 expression, 6/20 (30%) patients had positive expression in peritumoral lymphocyte infiltration. While 3/20 (15%) cases had PD-L1 either tumoral or peritumoral lymphocytes expression. Loss of MMR expression was present in 1 (5%) of 20 patients. PD-1 and/or PD-L1 expression cases tended to have deeper myometrial invasion and higher stage at presentation. Conclusions. Our results are suggestive of the roles of both PD-1 and PD-L1 in ECCCs as useful therapeutic biomarkers for immunotherapy.

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