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Histopathologic, Genetic and Molecular Characterization of Endometrial Cancer Racial Disparity.

ABSTRACT: In contrast to the decline in incidence and mortality of most other cancers, these rates are rising for endometrial cancer. Black women with endometrial cancer have earlier diagnosis, more aggressive histology, advanced stage and worse outcomes compared with their White counterparts. Socioeconomic status, a higher incidence of aggressive histology, and comorbid conditions are known factors leading to racial disparity in patients with endometrial cancer; nevertheless, they do not account for the entire racial disparity; which emphasizes the roles of molecular, histopathological and genetic factors. We performed a comprehensive review of all published scientific literature up to January 2021 reporting histopathologic, genetic and molecular factors associated with racial disparities in patients with endometrial cancer. The interactions and pathways of molecules reported to have significant differential expression in endometrial cancers from Black and White patients were identified with Ingenuity Pathway Analysis. The majority of studies compared Black and White patients; however, limited data are available for other racial and ethnic groups. Reported differences that could account for the worse survival of Black endometrial cancer patients include more aggressive histopathologies and molecular alterations, including upregulation of molecules driving cell cycle progression, and p53 and HER2/NEU signaling. Several of these molecules are targeted by existing pharmaceuticals. These findings encourage further study and the development of race-specific treatment strategies.

SUBMITTER: Javadian P

PROVIDER: S-EPMC8071317 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. A well recognized disparity by race in both incidence and survival outcome exists for this cancer. Specifically Caucasians are about two times more likely to develop endometrial cancer than are African-Americans. However, African-American women are more likely to die from this disease than are Caucasians. The basis for this disparity remains unknown. Previous studies have identified differences in the types and frequencies of gene mutations among endometrial cancers from Caucasians and African-Americans suggesting that the tumors from these two groups might have differing underlying genetic defects. We performed a gene expression microarray study in an effort to identify differentially expressed transcripts between African-American and Caucasian women's endometrial cancers. Our gene expression screen identified a list of potential biomarkers that are differentially expressed between these two groups of cancers. Of these we identified a poorly characterized transcript with a region of homology to phospho serine phosphatase (PSPH) and designated phospho serine phosphatase like (PSPHL) as the most differentially over-expressed gene in cancers from African-Americans. We further clarified the nature of expressed transcripts. Northern blot analysis confirmed the message was limited to a transcript of under 1?kB. Sequence analysis of transcripts confirmed two alternate open reading frame (ORF) isoforms due to alternative splicing events. Splice specific primer sets confirmed both isoforms were differentially expressed in tissues from Caucasians and African-Americans. We further examined the expression in other tissues from women to include normal endometrium, normal and malignant ovary. In all cases PSPHL expression was more often present in tissues from African-Americans than Caucasians. Our data confirm the African-American based expression of the PSPHL transcript in endometrial cancer and also identify its expression in other tissues from African-Americans including ovary and ovarian cancer. PSPHL represents a candidate gene that might influence the observed racial disparity in endometrial and other cancers.

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Histopathologic, Genetic and Molecular Characterization of Endometrial Cancer Racial Disparity.

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