Haptoglobin Expression in Endometrioid Adenocarcinoma of the Uterus

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Haptoglobin mRNA levels and protein localization were elevated in endometrioid adenocarcinoma and adjacent endometrium compared to normal endometrium, suggesting diagnostic utility.

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The paper investigated haptoglobin (Hp) mRNA expression and cellular localization in uterine endometrioid adenocarcinoma and in adjacent non-affected endometrium, using quantitative PCR and immunohistochemistry on tumor biopsies, adjacent tissue, and control endometrium from healthy women. Hp mRNA levels were significantly higher in endometrioid adenocarcinoma and adjacent non-affected endometrial tissues than in normal endometrium, but Hp levels did not correlate with cancer stage or grade, and Hp protein was found in both stromal and glandular epithelial cells of tumors and adjacent tissue, unlike control endometrium. A key limitation acknowledged implicitly by the study design is that it does not establish clinical performance of Hp as a marker beyond expression differences. This paper is centrally about adenomyosis and/or endometriosis? Specifically, it relates to endometriosis by building on prior findings that Hp is localized to stroma in endometriotic lesions and in eutopic endometrium from women with endometriosis, and it examines Hp expression patterns in an endometrioid adenocarcinoma context where endometriosis-linked biology is implicated.

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Abstract

Objective Elevated serum haptoglobin (Hp) concentrations have been reported in patients with malignant diseases. We have shown that Hp is produced by and localizes only in the stroma and not the epithelium of endometriotic lesions, which share many characteristics of carcinoma. Furthermore, Hp mRNA and protein are found exclusively in the stroma of eutopic endometrium from women with endometriosis and not those without endometriosis. We hypothesized that characteristic patterns of Hp gene expression and protein localization in endometrioid adenocarcinoma of the uterus may provide insight into the clinical utility of Hp as a tumor marker or alternative therapeutic approach.

Methods

Biopsies of endometrioid adenocarcinoma tumors of the uterus and their adjacent nonaffected endometrium were collected. Normal endometrium was collected from healthy women. Haptoglobin messenger RNA (mRNA) levels were quantified by quantitative polymerase chain reaction (Q-PCR). Haptoglobin protein cell-specific localization was identified by immunohistochemistry.

Results

Haptoglobin mRNA levels were significantly greater (P < .005) in endometrioid adenocarcinoma and adjacent non-affected endometrial tissues than normal endometrium. No correlation was found between Hp levels and cancer stage (P = .673) or grade (P = .739). Haptoglobin protein localized in both stromal and glandular epithelial cells of endometrioid adenocarcinoma and their adjacent nonaffected tissue but not in control endometrium.

Conclusions

Our results have identified, for the first time, unique patterns of Hp mRNA expression and protein localization in the stromal and glandular epithelial cells of endometrioid adenocarcinoma of the uterus. We propose that this unique pattern of endometrioid adenocarcinoma Hp expression may be developed as a novel diagnostic marker. Modulation of Hp, with its immunomodulatory and angiogenic properties, may generate novel methods of prevention or treatment for endometrial cancer. Similar content being viewed by others

References

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Sci. 17, 47–55 (2010). https://doi.org/10.1177/1933719109346331 Published: Issue date: DOI: https://doi.org/10.1177/1933719109346331

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MeSH descriptors

Carcinoma, Endometrioid Endometrial Neoplasms Haptoglobins Adult Analysis of Variance Carcinoma, Endometrioid Carcinoma, Endometrioid Endometrial Neoplasms Endometrial Neoplasms Epithelial Cells Epithelial Cells Female Gene Expression Regulation, Neoplastic Haptoglobins Haptoglobins Humans Immunohistochemistry Middle Aged Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger

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